BLACK PEPPER AND HEALTH CLAIMS: A COMPREHENSIVE TREATISE

For Peer Review O

nly

BLACK PEPPER AND HEALTH CLAIMS A COMPREHENSIVE

TREATISE

Journal Critical Reviews in Food Science and Nutrition

Manuscript ID BFSN-2011-0286R1

Manuscript Type Review

Date Submitted by the Author

10-Mar-2011

Complete List of Authors Butt Masood National Institute of Food Science and Technology University of Agriculture Faisalabad Pasha Imran University of Agriculture Faisalabad National Institute of Food Science and Technology Sultan Tauseef Bahauddin Zakariya University Dept of Food Sciences Randhawa Muhammad University of Agriculture Faisalabad National Institute of Food Science and Technology

Saeed Farhan University of Agriculture Faisalabad National Institute of Food Science and Technology Ahmad Waqas University of Agriculture Faisalabad National Institute of Food Science and Technology

Keywords Spices Black pepper Piperine Nutraceutical

URL httpmcmanuscriptcentralcombfsn Email fergcfoodsciumassedu

Critical Reviews in Food Science and Nutrition

For Peer Review

Only

1

TYPE OF ARTICLE Review article 1

TITLE BLACK PEPPER AND HEALTH CLAIMS A COMPREHENSIVE 2

TREATISE 3

4

5

1 Masood Sadiq Butt 6

National Institute of Food Science and Technology 7

University of Agriculture Faisalabad 8

9

2 Imran Pasha 10



13

3 Muhammad Tauseef Sultan 14

Department of Food Sciences 15

Bahauddin Zakariya University Multan 16

17

4 M Atif Randhawa 18



21

5 Farhan Saeed 22



25

6 Waqas Ahmad 26



29

30

daggerCorresponding author 31

Dr Muhammad Tauseef Sultan 32


Bahauddin Zakariya University 34

Multan Pakistan 35

Contact No 0092-333-9949100 36

Email tauseefsultanhotmailcom 37

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BLACK PEPPER AND HEALTH CLAIMS A COMPREHENSIVE TREATISE Masood Sadiq Butt a Imran Pasha a M Tauseef Sultan b M Atif Randhawa a

Farhan Saeed a and Waqas Ahmed a a National Institute of Food Science and Technology University of Agriculture Faisalabad

b Department of Food Sciences Bahauddin Zakariya University Multan

ABSTRACT

For millennia spices have been an integral part of human diets and commerce

Recently the widespread recognition of diet-health linkages bolsters their dietary

importance The bioactive components present in them are of considerable significance

owing to their therapeutic potential against various ailments They provide

physiological benefits or prevent chronic ailment in addition to the fundamental

nutrition and often included in the category of functional foods Black pepper (Piper

Nigrum L) is an important healthy food owing to its antioxidant antimicrobial potential

and gastro-protective modules Black pepper with piperine as an active ingredient

holds rich phytochemistry that also includes volatile oil oleoresins and alkaloids More

recently cell-culture studies and animal modeling predicted the role of black pepper

against number of maladies The free-radical scavenging activity of black pepper and its

active ingredients might be helpful in chemoprevention and controlling progression of

tumor growth Additionally the key alkaloid components of Piper Nigrum ie piperine

assist in cognitive brain functioning boost nutrientrsquos absorption and improve

gastrointestinal functionality In this comprehensive treatise efforts are made to

elucidate the antioxidant antimicrobial anti-inflammatory gastro-protective and anti-

depressant activities of black pepper Moreover the synergistic interaction of black

pepper with different drugs and nutrients is the limelight of the manuscript However

the aforementioned health promoting benefits associated with black pepper are proven

in animal modeling Thus there is a need to conduct controlled randomized trials

(CRTrsquos) in human subjects cohort studies and meta-analyses Such future studies

would be helpful in recommending its application in diet-based regimens to prevent

various ailments

Key words Spices Black pepper Piperine Functional properties Nutraceutical

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I Introduction 1

In the recent era efforts have been directed to establish scientific rationale for health 2

improving potential of functional and nutraceuticals foods Innovations in the 3

nutrigenomics and proteomics further reflected the importance of dietary interventions 4

to prevent and cure various maladies In this regard prevention of cardiovascular 5

disorders (CVD) cancer insurgence diabetes mellitus Alzheimerrsquos disease and variety 6

of inflammatory ailments through dietary modules is of prime consideration 7

(Chonpathompikunlert et al 2010) The list of healthy foods marketed with distinct 8

health claims is long enough However spices and their bioactive components are more 9

promising candidates for their inclusion in diet-based regimens to improve human 10

health (Butt et al 2009)Their different parts including dried seed bark fruit root and 11

flower are in use as food adjuncts that impart flavor aroma and color to foods 12

(Srinivasan 2008 Singletary 2010) 13

The demarcation line between culinary and therapeutic use of spices has been a bit hazy 14

from ancient times to the present era (Srinivasan 2005a) The health promoting 15

potential of these foods are numerous but improving digestive system mediating 16

inflammation antimicrobial chemo-protective and neuroprotective tasks are of greater 17

significance (Duessel et al 2008) Recently well-documented evidence supported their 18

ability to prevent cancer insurgence (Christine and Kaefer 2008 Butt and Sultan 2010) 19

However the claims are based on animal studies thus there is a need to study their 20

health claims in human subject in order to warrant their pharmaceutical application to 21

cure various maladies 22

Of the various spices black pepper (Piper Nigrum L) holds a prominent position and is 23

acknowledged as ldquoKing of Spicesrdquo (Nisha et al 2009) It has manifold functional uses in 24

the traditional food formulations kitchens perfumery traditional medicine and even 25

in beauty care (De-Souza et al 2005 Srinivasan et al 2004) Black pepperrsquos pungency 26

and flavor is due to presence of alkaloid piperine volatile oil and oleoresins (Zachariah 27

et al 2010) In Indian folklore medicine it is mainly used as an immune enhancer (Bang 28

et al 2009) and to treat against diarrhea asthma chronic indigestion gastric ailments 29

colic insomnia and epilepsy (Chaudhry and Tariq 2006 Agbor et al 2006 Fu et al 30

2010) The review is an effort to present the comprehensive treatise regarding the 31

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botanical classification and rich phytochemistry of black pepper The health promoting 1

potentials associated with its consumptions are the limelight of the manuscript The 2

details are described in their respective heading herein 3

II Botanical classification and phytochemistry 4

Black pepper belongs to Piperaceae family that comprises over one thousand species 5

with tropical and subtropical distribution (Table 1) It is commonly known as 6

peppermint black pepper kaali-mirch and black gold The coastal areas of India are its 7

prime origin but nowadays its plantation is extended to other parts of the globe too like 8

Vietnam Ceylon Malaysia Indonesia and Brazil (Thanuja et al 2002 Srinivasan 2008 9

Polovka and Suhaj 2010) 10

Place Table 1 here 11

Black pepper is dried form of un-ripened green berries and heat provided during 12

cooking aids in sudden burst of the cell walls The process further boosts enzymatic 13

reactions resulting in greater color changes leading to blackish tonality Black pepper 14

dried fruit is frequently refers as peppercorns (approximately 5 mm in size) The 15

peppercorns are rich in vitamin A and K in addition to dietary fiber calcium 16

magnesium potassium manganese phosphorous and β-carotene Some other products 17

from black pepper are ground pepper oleoresin and pepper oil (Utpala et al 2008 18

Zachariah et al 2010) 19

Black pepper with piperine as an active ingredient contains volatile oil oleoresins and 20

alkaloids Major alkaloids present in black pepper are piperine chavicine piperidine 21

and piperetine (Shaikh et al 2006) The terpenes steroids lignans flavones and 22

alkamides are other primary constituents (Musenga et al 2007 Murthy and 23

Bhattacharya 2008) Black pepper essential oil contributes towards the aroma oleoresin 24

contributes towards the overall taste and the alkaloid piperine imparts pungency 25

(Zachariah et al 2010) The briefs about the phytochemistry of the black pepper are 26

presented in Table 2 The detailed description of major components is discussed herein 27


A Piperine 29

In 1820 Danish chemist Hans Christian Orstedt isolated piperine for the first time The 30

relative m-olecular mass of piperine (C17H19O3N) ([1-[5-[1 3-benzodioxol-5-yl]-1-oxo-2 31

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4 pentadienyl piperidine) is 28533 g molminus1 and it contains 7155 carbon 1682 1

oxygen 491 nitrogen and 671 hydrogen It is yellow crystalline substance having a 2

melting point of 128ndash130degC (McNamara et al 2005) It is insoluble in water and acts as 3

weak base which on hydrolysis with nitric acid or aqueous alkali succumb to volatile 4

base piperidine (C5H11N) In contrary the acidic product of hydrolysis is piperine acid 5

(C12H19O4 mp 216ndash217degC) that further exists in four isomeric forms (Parmar et al 6

1997) 7

Piperine is tasteless due to the three isomers which are weakly pungent but its 8

stereoisomer ldquochavicinerdquo imparts characteristic pungency to the black pepper as stated 9

earlier (Bandhopadhyay et al 1990) Piperine is highly sensitive to light so solution 10

should not be exposed to direct light Piperine and its allied components like piperidine 11

and chavicine are responsible for pungent properties of black pepper (Badmaev et al 12

2000 Kaefera and Milne 2008) 13

Solvent extraction systems using ethanol as solvent are employed for the extraction of 14

piperine from black pepper (Naseri and Yahyavi 2008) The reverse phase high-15

performance liquid chromatography (R-HPLC) and spectrophotometer can be used for 16

its estimation The spectrophotometeric method invariably yields elevated results thus 17

HPLC method is more reliable (Wood et al 1988 Sowbhagya et al 1990) 18

The piperine is important for its health provoking potential described in later section of 19

the aritlce Briefly it facilitates the digestion and reduces the food passage time in 20

intestine by improving the digestive enzyme stimulation and saliva secretion In 21

addition to gastric protective functions piperine extends its services in liver protection 22

and bio-absorption of micronutrients vitamins and trace elements It helps increasing 23

the bioavailability of many types of drugs and phytochemicals thus act as nutrient 24

enhancer (Snyman et al 2001 Capasso et al 2002 Kumoro et al 2009) 25

B Essential oil 26

The essential oil of Black pepper (about 1ndash3) appears as a colorless to greenish liquid 27

with spicy (peppery) aroma It has characteristic odor reminiscent with flashpoint of 28

54degC specific gravity (0860 - 0884) and refractive index (1478 - 1488) at 20degC The 29

optical rotation (-1deg to -23deg) of black pepper oil is levorotatory (George et al 1988 30

Shankaracharya et al 1997) The extraction of essential oil can be carried out using 31

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various methods ie liquid carbon dioxide steam distillation and solid-phase micro 1

extraction (SPME) The nutrient and volatile components can be estimated through 2

column chromatography gas chromatography (GC) and gas-chromatography mass 3

spectrometer (Tipsrisukond et al 1998 Ferreira and Meireles 2002) 4

Until now 46 compounds are discovered The major components included are (E)-5

ocimene guaiene (Z) (E)-farnesol guaiol and cadinol Sabinene carophyllene and 6

terpinen-4-ol are present in appreciable quantities Other imperative sesquiterpene 7

hydrocarbons are bisabolene cadinenes calamenene copaene cubebenes ar-8

curcumene elemenes farnesene guaiene humulenes isocaryophyllene muurolene 9

santalene selinenes ledene sesquisabinene and zingiberene (Ao et al 1998 Zachariah 10

and Parthasarathy 2008 Renjie et al 2010) 11

C Phenolic compounds 12

The black pepper is rich in potent phenolic acids and antioxidants It is therefore 13

important spice for ameliorating oxidative stress The phenolic components of black 14

pepper are mixture of the glycosides of phenolic acids and flavonol glycosides (Renjie et 15

al 2010) Previously Parmar et al (1997) listed the flavonol constituents from black 16

pepper ie isoquercetin quercetin 3-β-D-rutinoside isorhamnetin kaempferol-3-o-β-17

galactoside kaempferol 3-arabinoside and quercetin-3-o-β-D rutinoside Overall the 18

black pepper contains the appreciable quantities of certain bioactive molecules that are 19

helpful in reducing the extent of various maladies 20

III Nutraceutical and Functional Scenario 21

The black pepper is used in conventional medicines as food adjunct to improve 22

digestive system through various modules ie better appetite amp absorption and 23

controlling dyspepsia amp fleshiness However the existing health problems that concern 24

mankind primarily include cardiovascular disorders diabetes mellitus inflammatory 25

disease and cancer insurgence (Chonpathompikunlert et al 2010) Several animal 26

studies explicated the role of black Pepper as preventive agent against these maladies 27

(Szallasi 2005 Politeo et al 2006) Some highlights of the health promoting potential of 28

bioactive molecules present in black pepper are presented in Table 3 However the 29

details of its potential health promoting benefits are described herein 30


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A Antioxidant Potential 1

Oxidation is an inevitable process observed in body cells coupled with some 2

undesirable responses that include production of reactive oxygen species (ROS) ROS 3

are widely accepted as the causative agent responsible for various ailments ie cancer 4

inflammation atherosclerosis and aging (Butt et al 2009) Excessive production of ROS 5

outplays the defense capabilities of body resulting in oxidative stress (Seifried et al 6

2007) A considerable number of spices and aromatic herbs are known to possess 7

antioxidant potential ought to the presence of bioactive molecules in them (Liu and Ng 8

2000) 9

In this regard Saxena et al (2007) established positive correlation between antioxidant 10

activity (AOA) and phenolic contents (PC) present in plants (r=-047) However 11

coefficient of correlation and determination is higher for spices (r=-086 and R2 =74 12

respectively) Black pepper holds significant antioxidant activity as 50 inhibition of 13

free radicals can be achieved with 043mg In some earlier studies conducted by Gulccedilin 14

(2005) it was observed that water and ethanol extracts (75 microgml) of black pepper show 15

955 and 933 inhibition of lipid-peroxidation respectively The inhibition ought to 16

total phenolics content ie 543 and 428microgmg respectively Saxena et al (2007) 17

reported higher quantities of polypheols ie 191mg100g Determination of antioxidant 18

activity through some In vitro trials generated some conclusive evidences In this 19

regard (Kapoor et al 2009) observed high antioxidant activities of black pepper 20

essential oil and oleoresins as compared to synthetic antioxidants Likewise Su et al 21

(2007) indicated that black pepper is a potential dietary source of natural antioxidants 22

Therefore presence of these functional ingredients in black pepper makes it a strong 23

candidate to ameliorate oxidative stress (Mittal and Gupta 2000) Gulccedilin (2005) 24

attributed these actions to its strong hydrogen-donating ability metal chelating and 25

effectiveness to scavenge free radicals Additionally synergistic effects of piperine with 26

some other antioxidants like curcumin also assign valuable position to black pepper in 27

disease prevention strategies related to ROS and allied species (Aggarwal 2010) 28

The animal modeling using high-fat diets can be utilized to assess the antioxidant 29

activities of plants In this regard the production of thiobarbituric acid reactive 30

substances (TBARS) and conjugated dienes (CD) is used as indices of oxidative damage 31

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Whilst imbalance in activities of antioxidant enzymes including superoxide dismutase 1

(SOD) catalase (CAT) glutathione-S-transferase (GST) glutathione peroxidase (GPx) 2

and glutathione contents are indices of reduced antioxidant status of the body 3

(Ramasamy and Namasivayam 2006) Vijayakumar et al (2004) reported that 4

supplementation of black pepperpiperine lowered oxidative damage and modulated 5

the enzyme systems functioning in the body (Vijayakumar and Nalini 2006) Rauscher 6

et al (2007) used diabetes mellitus induction as a model of oxidative damage and 7

application of piperine 10mgkgday ip reversed the diabetes mediated changes in 8

Sprague Dawley rats The effects are attributed to presence of antioxidants that further 9

results in reduced LDL-oxidation via modulation of prostaglandins and leukotrienes 10

synthesis (Srinivasan 2005b) 11

In the nutshell black pepper holds antioxidant potential but needs further testing 12

through controlled randomized trials (CRTrsquos) The results from such studies would 13

guarantee utilization of black pepper and its bioactive molecules as natural antioxidant 14

in food chain and diet based strategies to prevent various maladies 15

B Anti-inflammatory Potential 16

The process of inflammation can lead to the development of various ailments that 17

include arthritis Alzheimerrsquos Parkinsonrsquos disease and even cancer insurgence is also 18

linked with inflammatory burst The mechanism to cope with the inflammation 19

comprises of many pathways that also include inhibition of enzymes responsible for 20

inflammatory cascade (Mueller et al 2011) Diets containing functional ingredients 21

hold anti-inflammatory potential (Monika et al 2010) Recent pharmacological studies 22

conducted at animals and cell levels have shown that black pepper and its active 23

ingredients piperine might be useful against these undesirable responses (Gupta et al 24

2000 Selvendiran et al 2003 Sabina et al 2011) 25

Eventually anti-inflammatory activities of black pepper are reported for the first time 26

some two decades ago Mujumdar et al (1990) indicated that piperine mitigate the acute 27

inflammatory process through stimulating the pituitary adrenal axis Later Bang et al 28

(2009) strengthened the anti-inflammatory activities of piperine (20 amp 100 mgkgday) 29

through some in vitro trials They postulated that inhibition of interlukon (IL6) matrix 30

metalloproteinase (MMPs) prostaglandin E2 (PGE2) and activator protein 1 are 31

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possible routes for their said properties Recently Sabina et al (2011) reported that 1

piperine (50100ugml) suppressed the level of β-glucuronidase and lactate 2

dehydrogenase in dose-dependent manner Piperine along with some other 3

components can inhibit the expression of enzymes like 5-lipoxygenase and COX-1 that 4

are responsible for leukotriene and prostaglandin biosynthesis These effects 5

collectively are valuable to prevent degenerative disorders like rheumatoid arthritis too 6

(Stohr et al 2001 Lee et al 2008) 7

Overall the anti-inflammatory perspectives of black pepper and its active ingredients 8

should be tested in disease prevention and control associated with inflammation 9

C Antimicrobial Potential of Black Pepper 10

If we turn the pages of history we can see that since long plants were employed as 11

antimicrobial agents (Irkin and Korukluoglu 2009) Utilization of natural products 12

especially spices as antimicrobials is allied with dual benefits ie prevention of 13

infectious disorder and improving health Phytochemicals present in these products 14

hold antimicrobial potential and extensively explored in the recent epoch Amongst 15

phenolics possess well-documented antimicrobial potential (Weerakkody et al 2010) 16

Black pepper and piperine hold antimicrobial properties and can remarkably limit the 17

growth of Staphylococcus aureus (Sangwan et al 2008) S epidermidis and Salmonella typhi 18

(Arora and Kaur 1999) Additionally Singh et al (2005) further strengthened the notion 19

by the proof against Bacillus cereus and B subtilis Recently Weerakkody et al (2010) 20

enumerated the significant antimicrobial potential of black pepper Some extracts of 21

black pepper displayed excellent growth inhibition of bacteria like Staphylococcus 22

Bacillus and Streptococcus with minimum inhibitory concentrations (MIC) of 125 250 and 23

500ppm respectively (Karsha and Lakshmi 2010) Likewise pseudomonas was more 24

susceptible to black pepper followed by Escherichia coli Klebsiella and Salmonella (625 25

125 and 250ppm MIC respectively) 26

In this regard Mc-Mahon et al (1995) also reported the anti-parasitic behavior of black 27

pepperrsquos alkaloids against Giardia and Entamoeba species Similar studies by various 28

other scientists concluded their potential against trypanosomes and plasmodia One of the 29

interesting roles of black pepper is related to repellent potential against various insects 30

and rodent Scott et al (2002) observed that black pepper and other freshly ground 31

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peppers are sprinkled to repel many mammals It is also reported to be effective against 1

houseflies along with its ability to depress egg-laying (MacKinno et al 1997) The 2

extracted essential oil from black pepper can also be applied to protect grains from 3

insect damage and control worm infestations (Dorman and Deans 2000) Some 4

bioactive molecules of black pepper find their application in allelopathic control of 5

insect-pests owing to their efficacy (Gbewonyo et al 1993) Black Pepper oil also 6

demonstrated significant antimicrobial activity against animal pathogens (Bonjar 2004) 7

Overall black pepper holds substantial antimicrobial activity against various 8

microorganisms and can find different applications ranging from preserving foods to 9

prevent infections 10

D Gastrointestinal health and nutrient absorption 11

Black pepper and its active ingredients are commonly employed as traditional remedies 12

against gastric disturbances from time immemorial It is widely accepted that black 13

pepper is instrumental to prevent and cure gastrointestinal problems The black pepper 14

enhances the production of hydrochloric acid from stomach thus improving digestion 15

through stimulation of histamine H2 receptors In addition black pepper has 16

diaphoretic (promotes sweating) and diuretic (promotes urination) properties (Johri et 17

al 1992 Ononiwu et al 2002) 18

As far absorption of piperine is concerned it is absorbed from mucosal side (44-63) 19

that could be traced in intestinal tissue and serosal fluids (Suresh and Srinivasan 2007) 20

Piperine improves the functionality of gastrointestinal tract The mechanisms of action 21

include enhanced absorption of nutrients improved enzymes synthesis and perk-up 22

defense capabilities The examples include enhanced intestinal absorption of 23

methionine amp calcium ions trace elements (selenium) vitamins B and β-carotene 24

(Badmaev et al 2000 Capasso et al 2002) The amplified nutrient absorption is 25

dependent upon the positive changes in permeability of intestinal cells membranes 26

(Srinivasan 2007) Moreover it protects intestinal membranes from gastric secretions 27

and ROS damage owing to antioxidant potential Moreover black pepper significantly 28

enhanced the activities of antioxidant enzymes ie SOD catalase GR and GST These 29

mechanisms collectively lead to balanced mucosal health to provide gastro-protection 30

(Irani 2005 Chaudhry and Tariq 2006 Prakash and Srinivasan 2010) In addition to 31

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above black pepper and its active ingredients improve expression of some digestive 1

enzymes along with increase in the secretion of saliva These collectively lead to 2

facilitated digestion with reduced transit time in gastrointestinal tract (Kumoro et al 3

2009 Bang et al 2009 Kaefera and Milne 2008) 4

Recently Okumura et al (2010) presented the hypothesis that piperine intake may 5

decrease body weight and visceral fat accumulation through increased expression of 6

thermogenic protein uncoupling protein-1 in the mice Badmaev et al (1999) showed 7

that black pepper could speed the metabolic procedures that generate energy in the 8

human body Although the same process is responsible for sustaining weight loss but 9

recognized as playing an essential role in modulating nutrients absorption from diet 10

Moreover piperine increases the oxygen uptake when administered to perfuse hind 11

limbs of experimental rats (Srinivasan 2007 Eldershaw et al 1994) Pepper juice 12

amplifies intestinal absorption of different nutrients and piperine dose-dependently 13

restrained fatty acid oxidation in rat liver microsomes (Platel et al 2003 14

Tachakittirungrod et al 2007) 15

Black pepper along with its bioactive molecules can be used in constipation and 16

diarrhea The mode of action of black pepper and its bioactive molecules involves 17

concentration-dependent amp atropine-sensitive stimulant effect spontaneous 18

contractions similar to loperamide and nifedipine inhibition of naloxone-sensitive 19

effect Ca(2+) channel blocking (CCB) activity relaxant effect K+ (80 mM)-induced 20

contractions These mechanisms collectively leads to spasmodic (cholinergic) and 21

antispasmodic (opioid agonist and Ca (2+) antagonist) effects as narrated by Lambert et 22

al (2004) and Mehmood and Gilani (2010) Overall the results are quire conclusive to 23

warrant the utilization of black pepper and its ingredients to prevent and cure various 24

gastro-intestinal disorders 25

E Improvement in drugs amp phytochemicals delivery 26

The phytochemicals and nutrients are important to maintain the human health but issue 27

of their bioavailability needs researcherrsquos attention Some bioactive molecules work 28

synergistically to improve the absorption of each other Black pepper and piperine 29

improved the bioavailability of some phytochemicals like curcumin catechins etc The 30

mechanisms for claimed effects include 1) ability to promote the rapid absorption 2) 31

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protection from chemical reactions in the gastrointestinal tract and 3) protection against 1

oxidative damage (Agbor et al 2010 Singletary 2010) 2

The black pepper and piperine improve the bioavailability of many drugs In this 3

regard piperine enhances the oral bioavailability of carbamazepine and phenytoin 4

(drugs used to cure epilepsy) by improving their absorption (Pattanaik et al 2009) 5

Previously Pattanaik et al (2006) provided evidences for synergistic effects of piperine 6

(20mg) administered with phenytoin Likewise supplementation of 120 mg coenzyme 7

Q10 with piperine for 21 days produced a statistically significant (p = 00348) greater 8

area under the plasma curve (30) as compared to coenzyme Q10 alone (Badmaev et 9

al 2000) The results of efficacy studies conducted by Jin and Han (2010) suggest that 10

piperine significantly augments the oral exposure of fexofenadine in rats probably due 11

to the inhibition of P-glycoprotein-mediated cellular efflux during the intestinal 12

absorption (Lee et al 2006) In some studies utilization of black pepper or its active 13

ingredients including piperine increased the bioavailability of nimesulide (anti-14

inflammatory drug) Acute toxicity studies on mice revealed a reduction in lethal dose 15

(LD50) of the combination (980 mg kg-1) as compared to nimesulide (1500 mg kg-1) alone 16

(Gupta et al 2000) Likewise drugs like ampicillin and Norfloxacin mediate variety of 17

bacterial infections and co-administration of 20 mgkg of piperine can enhance their 18

effectiveness (Janakiraman and Manavalan 2008) 19

Piperine also boosts the bioavailability of important phytochemicals contained in other 20

foods eg bioactive components present in curcumin and green tea (Selvendiran et al 21

2003) Curcumin has been widely used as food additive and herbal medicine 22

throughout Asia The combination of piperine (25 mgkg ip 21 days) with curcumin 23

(20 and 40 mgkg ip 21 days) showed improved anti-immobility neurotransmitter 24

enhancing and monoamine oxidase inhibitory (MAO-A) effects of curcumin (Bhutani et 25

al 2009 Suresh and Srinivasan 2010) The combination of curcumin and piperine is 26

most likely to inhibit CYP3A CYP2C9 UGT and SULT metabolism within the 27

intestinal mucosa (Volak et al 2008) 28

Conclusively addition of black pepper or piperine to recipes amp meals can improve the 29

restorative worth of various spices and other foodstuffs (Nakatani et al 1986 30

Selvendiran et al 2003) Black pepper can enable us to reap optimum benefits from the 31

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medicinal phytochemicals found in other dietary spices Its bioavailability enhancing 1

properties makes black pepper one of the most important spices 2

F Neuroprotective potential of black pepper 3

Globally statistics are alarming regarding the mental and brain ailments According to 4

estimate more than 450 million people suffer from some nervous problems (Gupta et 5

al 2000) Amongst depression is leading source of distress and discomfort for more 6

than 20 of global population (Kessler et al 1994) Humans in a bid to find the way out 7

to these conditions have devised many possible methods yet are not so successful in this 8

arena (Dorman et al 2000 Fu et al 2010) 9

The neuroprotective role of functional foods has been highlighted in the recent past to 10

cure number of ailments In this regard antioxidant potential of black pepper and its 11

bioactive molecules is of considerable importance to improve brain function 12

(Wattanathorn et al 2008) Furthermore the supplementation of piperine (5 10 and 13

20mgkg bodyday) provides neuro-protection including improved cognitive function 14

(Hanumanthachar and Miland 2005 Lee et al 2005) Li et al (2007) previously 15

investigated the antidepressant-like effect of piperine (25 5 and 10 mgkg) Their 16

results revealed that piperine ameliorated the chronic mild stress due to changes in 17

sucrose consumption plasma corticosterone level and open field activity They 18

commented that up-regulation of the progenitor cell proliferation of hippocampus and 19

cytoprotective activities are responsible for antidepressant-like effect of piperine Later 20

Li et al (2007) added that piperine treatment up-regulated brain-derived neurotrophic 21

factor (BDNF) and mRNA expression Additionally Hu et al (2009) indicated that 22

piperine (10 amp 20 mgkg) improved the depression through reduction in ACTH and 23

CRH levels thus ultimately leading to modulating hypothalamic-pituitary-adrenal 24

(HPA) axis Recently Bhutani et al (2009) suggested to use piperine in combination 25

with curcumin for the treatment of depressive disorders The behavioral studies using 26

forced swimming test (FST) and tail suspension test (TST) revealed that piperine is 27

potent anti-depressant agent 10 amp 20 mgkg (Lee et al 2005 Mohit et al 2009 Liao 28

et al 2009) 29

Currently the number of patients suffering from Alzheimerrsquos disease is one of the 30

biggest challenges being faced by mankind (Filley 1995 Zarotsky et al 2003 Liston et 31

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14

al 2004) The scientists over the globe attempted to isolate some natural products 1

suitable against such disorders (Galli et al 2002 Youdim et al 2002 Jabeen et al 2007) 2

In one such study Chonpathompikunlert et al (2010) studied the effects of piperine in 3

rat modeling and observed that piperine (5 10 and 20 mgkg BW) significantly 4

improved memory impairment and neurodegeneration in hippocampus Piperine and 5

its analog (methyl piperate) have ability to restrain the monoamine oxidases (MAO) (Li 6

et al 2007 Naseri and Yahyavi 2008) that is one of suitable strategy to prevent 7

neurodegenerative problems such as Alzheimerrsquos and Parkinsonrsquos (Kong et al 2004 8

Edmondson et al 2007 Lee et al 2008) However the effects of piperine on 9

neurogenesis are not well demonstrated in human subjects but modes of actions could 10

possible be reduced extent of lipid peroxidation and acetylcholinesterase enzyme 11

(Youdim et al 2002) 12

Black pepper and its active ingredients can be supportive in treating various disorders 13

related to nervous systems that include depression Alzheimer epilepsy etc However 14

its pharmaceutical application cannot be warranted now owing to less number of 15

scientific investigations in human subjects Therefore as earlier stated that controlled 16

randomized trials should be conducted keeping in mind the above discussion to bring 17

meticulousness of the issues 18

G Black pepper against cancer 19

According to an estimate the prevalence of cancer can be reduced (30 to 40) with the 20

dietary habits (Anto et al 2002 Zhou et al 2003) Some population-based studies also 21

indicated that consumption of foods rich in bioactive molecules can decrease the risk of 22

various ailments especially cancer In this regard consumption of spices is positively 23

correlated with reduced risks of cancer incidence in Asian and Mediterranean regions 24

(Mohandes et al 1999) Even the higher risk of malignancies in developing economies 25

can be linked with the reduced intake of spices (Fleischauer et al 2000 Sloan 2005 26

Selvendiran et al 2005) 27

The anticancer perspectives of black pepper include modulation of phase-I phase-II 28

detoxification systems inhibition of lipid peroxidation and indeed improvement in 29

antioxidants status (Selvendiran and Sakthisekaran 2004) In this regard Zhou et al 30

(2003) presented the evidences that the positive anticancer effects of piperine against 31

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15

benzo-pyrene induced lung carcinogenesis in mice model are due to its ability to 1

interaction with cytochrome P450 enzyme syste Later Selvendiran et al (2004) 2

explicated that piperine exhibited in vitro and in vivo dose-dependent inhibition of 3

phase-I detoxification system (Bhardwaj et al 2002) Moreover piperine modulated the 4

mitochondrial tricarboxylic acid cycle and glutathione-metabolizing enzymes in animal 5

model lung carcinogenesis (Thirunavukkarasu et al 2001 Vijayakumar et al 2004 6

Suresh and Srinivasan 2006) Later Vellaichamy et al (2009) examined the 7

chemopreventive potential of piperine (50mgkg) against 712-8

dimethylbenz[a]anthracene (DMBA)-induced skin carcinogenesis Piperine modulated 9

the phase I amp II detoxification system effectively thus ameliorating lipid peroxidation 10

In addition to aforementioned effects the improvements in antioxidants status to 11

normal are of significant importance for health care Likewise Krishnakumar et al 12

(2009) observed similar results in oral cancer bearing animals Earlier Nalini et al 13

(1998) observed that black pepper may protect the colon cancer by decreasing the 14

activity of β-glucuronidase and mucinase Pellitorine (terpinoids present in black 15

pepper) showed strong cytotoxic activities against HL60 and MCT-7 cell lines (Ee et al 16

2010) Black pepper also counteracts cancer development directly (Selvendiran et al 17

2004) through modification in enzyme kinetics to control the protein level in blood 18

(Polovka and Suhaj 2010) In another study Bogomolny et al (2008) supported some 19

earlier studies that piperine owing to its potent antioxidant property can reduce protein 20

expression thus modulating cell proliferation and transformation (Selvendiran et al 21

2006) Research has revealed that pepper exerts a free-radical scavenging activity that 22

assists in controlling the progression of some cancers In some conditions the same 23

property can be useful in reducing the growth of cancer cells (Yadav and Bhatnagar 24

2007) More recently Liu et al (2010) postulated that nearly all bioactive molecules of 25

black pepper can suppress TNF-induced NF-kappaB activation The extracts of black 26

pepper at 200 microgmL and its compounds at 25 microgmL inhibited lipid peroxidation 27

by 45-85 COX enzymes by 31-80 and cancer cells proliferation by 35-868 28

Piperine when used in combination with curcumin yielded some promising results as 29

their combination restored the status of lipid peroxidation antioxidants and detoxifying 30

agents in DMBA-induced bone marrow cancer (Manoharan et al 2009) Furthermore 31

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16

black pepper and cardamom extracts collectively enhance the cytotoxic activity of 1

natural killer cells that indicate their potential anti-cancer effects (Majdalawieh and 2

Carr 2010) 3

The black pepper and its components are also effective in reducing the extent of toxicity 4

of certain components The drastic effects of some toxic compounds like DMBA carbon 5

tetrachloride tert-butyl hydroperoxide dioxin and AFB1 are mediated by black pepper 6

and piperine (60 microM) as elaborated by some scientists (Reen et al 1997 Koul and Kapil 7

1993 Amakura et al 2003 Han et al 2008) The undesirable effects of aforementioned 8

toxic metabolites are of serious concern for human amp animal health as they enter 9

through food chain and cause reproductive toxicity teratogenicity immune 10

dysfunction hepatotoxicity and endocrine changes (Schecter et al 2006 Ishida et al 11

2008) Researchers hypothesized that piperine may hinder hydrolysis of glucuronide 12

conjugates causing toxins and mucinase to be degraded (Kobayashi et al 2003 Nalini 13

et al 1998 Srinivasan 2007) The black pepper and its bioactive molecules hold 14

potential to prevent cancerous growth and are of important for their anti-genotoxicity 15

perspectives 16

H Other Health Benefits 17

The hypocholesterolemic and antioxidant property of black pepper has far-reaching 18

nutraceutical worth (Tachakittirungrod et al 2007) The increased levels of 19

triglycerides total amp low-density lipoprotein (LDL) cholesterol are major risk factors for 20

cardiovascular disorders Some dietary strategies can prevent prevalence and 21

pathogenesis of CVDrsquos The improvement in peroxisome proliferators-activated 22

receptor (PPAR)-α is one possible route to improve the lipid profile The piperine 23

exerted the highest trans-activational activities with EC (50) values of 84thinspmicroM and 49thinspmicroM 24

respectively (Mueller et al 2011) Earlier Taqvi et al (2008) explored underlying 25

mechanism behind cardiovascular effects of piperine (1 to 10 mgkg) It caused a dose-26

dependent decrease in mean arterial pressure (MAP) through inhibition of K+ (80 mM) 27

precontractions amp phenylephrine (PE) and Ca2+ channel blockade Piperine (20 28

mgkgday) decreased the blood pressure caused by the blockage of voltage-29

dependent calcium channels (Hlavackova et al 2010) 30

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17

One of the main common ailments in the world diabetes mellitus enforces a fabulous 1

health and social burden (McDonnell and Archbold 1996) The pathogenesis of diabetes 2

is dependent on many factors and glycation of the various proteins in the body is of 3

considerable importance The glycation of albumins and allied protein might lead to 4

change in nature structure and their biochemical activity Black pepper has inhibitory 5

effects on albumin glycation reaction (Dearlove et al 2008 Singletary 2010) Likewise 6

Saraswat et al (2009) reported inhibition of 40 to 90 (piperine 10 mgml) in the 7

formation of advanced glycation end-products (AGE) to lens proteins Black pepper 8

(IC50 02mgmL) showed excellent selectivity towards aldose reductase inhibition The 9

aforementioned discussion portrayed the message that inclusion of black pepper in 10

dietary strategies can be beneficial in management of diabetes and its complications 11

(Vijayakumar et al 2004 Saraswat et al 2008) However there is still needs for some 12

community-based trials for meticulousness 13

Black pepper extract has been studied by (Venkatasamy et al 2004) to treat skin 14

disorders ie vitilago that is characterized by lesions of depigmentation Ebihara et al 15

(2006) suggested that black pepper excavate and its main alkaloid piperine endorse 16

stimulatory effects on melanocyte proliferation and dendricity thus it can be used for 17

the treatment of vitiligo (Soumyanath et al 2006 Lin et al 2007) In humans black 18

pepper oil is one the strongest appetizer inhalation stimulates the swallowing in post 19

stroke patients with dysphagia Some other studies are also available regarding health 20

promoting potentials of black pepper However many of them are limited in their 21

applications owing to lack of animal studies 22

Conclusion 23

In the recent epoch much focus has been paid to functional and nutraceutical food The 24

health promoting prospective of such products is ought to bioactive components 25

present in them Black pepper owing to functional ingredients like piperine oleoresins 26

and essential oil is helpful in regulating gastrointestinal functionality It is also helpful 27

in mediating inflammation Black pepper can provide neuro-protection thus defending 28

the body from depression and Alzheimerrsquos The synergistic effect of black pepper in 29

enhancing the bioavailability of nutrients and drugs is of considerable importance 30

Overall the nutraceutical perspective of black pepper is of key importance for health 31

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18

care consultants However researcher concentration is immediately required to asses its 1

health promoting potential through controlled randomized trials (CRTrsquos) and cohort 2

studies Additional efforts are also required to asses its proper utilization in different 3

products and results of such studies would bring meticulousness of the concerns 4

References 5

Agbor A G Vinson A J Oben E J and Ngogang Y J (2010) Antioxidant effect of 6

herbs and spices on copper mediated oxidation of lower and very low density 7

lipoprotein China J Nat Med 8 114-120 8

Agbor G A Vinson J A Oben J E and Ngogang J Y (2006) Comparative analysis 9

of the in vitro antioxidant activity of white and black pepper Nutr Res 26 659-10

663 11

Aggarwal B B (2010) Targeting inflammation-induced obesity and metabolic diseases 12

by curcumin and other nutraceuticals Annu Rev Nutr 30 173-199 13

Amakura Y Tsutsumi T Sasaki K Yoshida T and Maitani T (2003) Screening of 14

the inhibitory effect of vegetable constituents on the aryl hydrocarbon receptor-15

mediated activity induced by 2378 tetrachlorodibenzo-p-dioxin Biol Pharm 16

Bull 26 1754-1760 17

Anto R J Mukhopadyah A Denning K and Aggarwal B B (2002) Curcumin 18

induces apoptosis through activation of caspase-8 BID cleavage and cytochrome 19

c release its suppression by ectopic expression of Bcl-2 and Bcl-xl Carcinogenesis 20

23 143-150 21

Ao P Hu S and Zhao A (1998) Essential oil analysis and trace element study of the 22

roots of Piper Nigrum L Zhongguo Zhong Yao Za Zhi 23 42-63 23

Arora D S and Kaur J (1999) Antimicrobial activity of spices Int J Antimicrob 24

Agents 12 257-262 25

Badmaev V Majeed M and Norkus E (1999) Piperine an alkaloid derived from 26

black pepper increases serum response of beta-carotene during 14-days of oral 27

beta-carotene supplementation Nutr Res 193 381-388 28

Badmaev V Majeed M and Prakash L (2000) Piperine derived from black pepper 29

increases the plasma levels of coenzyme Q10 following oral supplementation J 30

Nutr Biochem 11 109-113 31

Page 18 of 42



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19

Bandhopadhyay C Narayan V S and Variyar P S (1990) Phenolics of green pepper 1

berries Piper Nigrum L J Agric Food Chem 38 1696-1699 2

Bang J S Oh da H Choi H M Sur B J Lim S J Kim J Y Yang H I Yoo M C 3

Hahm D H and Kim K S (2009) Anti-inflammatory and antiarthritic effects of 4

piperine in human interleukin 1beta-stimulated fibroblast-like synoviocytes and 5

in rat arthritis models Arthritis Res Ther 11 R49 6

Bhardwaj R K Glaeser H Becquemont L Klotz U Gupta S K and Fromm M F 7

(2002) Piperine a major constituent of black pepper inhibits human p-8

glycoprotein and CYP3A4 J Pharmacol Exp Ther 302 645-650 9

Kaefera C M and Milne J A (2008) The role of herbs and spices in cancer prevention 10

J Nutr Biochem 19 347-361 11

Bhutani M K Bishnoi M and Kulkarni S K (2009) Anti-depressant like effect of 12

curcumin and its combination with piperine in unpredictable chronic stress-13

induced behavioral biochemical and neurochemical changes Pharmacol Biochem 14

Behav 92 39-43 15

Bogomolny E Argov S Mordechai S and Huleihel M (2008) Monitoring of viral 16

cancer progression using FTIR microscopy a comparative study of intact cells 17

and tissues Biochim Biophys Acta 1780 1038-1046 18

Bonjar G H S (2004) Screening for antibacterial properties of some Iranian plants 19

against two strains of Escherichia Coli Asian J Plant Sci 3 310-314 20

Butt M S and Sultan M T (2010) Nigella sativa Reduces the risk of various maladies 21

Crit Rev Food Sci Nutr 50 654-665 22

Butt M S Sultan M T Butt M S and Iqbal J (2009) Garlic naturersquos protection 23

against physiological threats Crit Rev Food Sci Nutr 49 538-551 24

Capasso R Izzo A A Borrelli F Russo A Sautebin L Pinto A Capasso F and 25

Mascolo N (2002) Effect of Piperine the active ingredient of black pepper on 26

intestinal secretion of mice Life Sci 71 2311-2317 27

Chaudhry N M A and Tariq P (2006) Bactericidal activity of black pepper bay leaf 28

aniseed and coriander against oral isolates Pak J Pharm Sci 19 214-218 29

Page 19 of 42



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20

Chonpathompikunlert P Wattanathorn J and Muchimapura S (2010) Piperine the 1

main alkaloid of Thai black pepper protects against neurodegeneration and 2

cognitive impairment in animal model of cognitive deficit like condition of 3

Alzheimerrsquos disease Food Chem Toxicol 48 798ndash802 4

Christine M and Kaefer J A M (2008) The role of herbs and spices in cancer 5

prevention J Nutr Biochem 19 347-361 6

Dearlove R P Greenspan P Hartle D K Swanson R B and Hargrove J L (2008) 7

Inhibition of protein glycation by extracts of culinary herbs and spices J Med 8

Food 11 275-281 9

De-Souza E L Stamford T L M Lima E O Trajano V N and Filho J M B (2005) 10

Antimicrobial effectiveness of spices an approach for use in food conservation 11

systems Braz Arch Biol Technol 48 549-558 12

Dorman H J D and Deans S G (2000) Antimicrobial agents from plants 13

antibacterial activity of plant volatile oils J Appl Microbiol 88 308-316 14

Duessel S Heuertz R M and Ezekiel U R (2008) Growth inhibition of human colon 15

cancer cells by plant compounds Clin Lab Sci 21 151-7 16

Ebihara T Ebihara S Maruyama M Kobayashi M Itou A Arai H and Sasaki H 17

(2006) A randomized trial of olfactory stimulation using black pepper oil in 18

older people with swallowing dysfunction JAGS 54 1401-1406 19

Edmondson D E Binda C and Mattevi A (2007) Structural insights into the 20

mechanism of amine oxidation by monoamine oxidases A and B Arch Biochem 21

Biophys 464 269-276 22

Ee G C Lim C M Rahmani M Shaari K and Bong C F (2010) Pellitorine a 23

potential anti-cancer lead compound against HL6 and MCT-7 cell lines and 24

microbial transformation of piperine from Piper Nigrum Molecules 15 2398-404 25

Eldershaw T P Colquhoun E Q Bennett K L Dora K A and Clark M G (1994) 26

Resiniferatoxin and piperine capsaicin-like stimulators of oxygen uptake in the 27

perfused rat hind limb Life Sci 55 389-397 28

Ferreira S R S and Meireles M A A (2002) Modeling the supercritical fluid 29

extraction of black pepper Piper Nigrum L essential oil J Food Engg 54 263-269 30

Page 20 of 42



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21

Filley C M (1995) Alzheimerrsquos disease itrsquos irreversible but not untreatable Geriatrics 1

50 18ndash23 2

Fleischauer A T Poole C and Arab L (2000) Garlic consumption and cancer 3

prevention metaanalyses of colorectal and stomach cancers Am J Clin Nutr 72 4

1047-1052 5

Fu M Sun Z H and Zuo H C (2010) Neuroprotective effect of piperine on 6

primarily cultured hippocampal neurons Biol Pharm Bull 33 598-603 7

Galli R L Shukitt-Hale B Youdim K A and Joseph J A (2002) Fruit polyphenolics 8

and brain aging nutritional interventions targeting age-related neuronal and 9

behavioral deficits Ann N Y Acad Sci 959 128-132 10

Gbewonyo W S K Candy D J and Anderson M (1993) Structure activity 11

relationships of insecticidal amides from Piper Guineese root J Pestic Sci 37 57-12

66 13

George K M Joy M T Chandran C V and Verghese J (1988) The angular rotation 14

of black pepper oil Indian Perfum 32 51-54 15

Gulccedilin I (2005) The antioxidant and radical scavenging activities of black pepper (Piper 16

Nigrum) seeds Int J Food Sci Nutr 56 491-9 17

Gupta S K Bansal P Bhardwaj R K Velpandian T (2000) Comparative 18

antinociceptive anti-inflammatory and toxicity profile of nimesulide vs 19

nimesulide and piperine combination Pharmacol Res 41 657ndash662 20

Han Y Chin T T M and Lim L Y (2008) In vitro and in vivo evaluation if the 21

effects of piperine on P-GP function and expression Toxicol Appl Pharmacol 230 22

283-289 23

Hanumanthachar J and Miland P (2005) Effects of piperine on memory and behavior 24

mediated via monoamine neurotransmitters J Trad Med 22 39-43 25

Hlavackova L Urbanova A Ulicna O Janega P Cerna A and Babal P (2010) 26

Piperine active substance of black pepper alleviates hypertension induced by 27

NO synthase inhibition Bratisl Lek Listy 111 426-431 28

Hu Y Liao H B Liu P Guo D H and Wang Y Y (2009) Antidepressant effects of 29

piperine and its neuroprotective mechanism in rats Zhong Xi Yi Jie He Xue 30

Bao 7 667-70 31

Page 21 of 42



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22

Irani F (2005) An encounter with ayurveda aromatherapy J Aromather 3 29-35 1

Irkin R and Korukluoglu M (2009) Growth inhibition of pathogenic bacteria and 2

some yeasts by selected essential oils and survival of L monocytogenes and C 3

albicans in apple-carrot juice Foodborne Pathog Dis 6 387-394 4

Ishida T Ishizaki M Tsutsumi S Ishii Y and Yamada H (2008) Piperine a Pepper 5

Ingredient Improves the Hepatic Increase in Free Fatty Acids Caused by 2378-6

Tetrachlorodibenzo-p-dioxin J Health Sci 545 551-558 7

Jabeen B Badaruddin M Ali R and Haleem D J (2007) Attenuation of 8

restraintinduced behavioral deficits and serotonergic responses by stabilized rice 9

bran in rats Nutr Neurosci 10 11-16 10

Janakiraman K and Manavalan R (2008) Studies on effect of piperine on oral 11

bioavailability of ampicillin and norfloxacin Afr J Tradit Complement Altern 12

Med 5 257-262 13

Jin Z Borjihan G Zhao R Sun Z Hammond G B and Uryu T (2009) 14

Antihyperlipidemic compounds from the fruit of Piper Longum L Phytother Res 15

23 1194-1196 16

Jirovetz L Buchbauer G Ngassoum M B and Geissler M (2002) Aroma compound 17

analysis of Piper Nigrum and Piper guineense essential oils from Cameroon using 18

solid-phase microextraction-gas chromatography solid-phase microextraction-19

gas chromatography-mass spectrometry and olfactometry J Chromatogr A 976 20

265-275 21

Johri R K Thusu N Khajuria A and Zutshi U (1992) Piperine-mediated changes 22

in the permeability of rat intestinal epithelial cells the status of gamma-glutamyl 23

transpeptidase activity uptake of amino acids and lipid peroxidation Biochem 24

Pharmacol 43 1401-1407 25

Kapoor I P S Singh B Singh G De-Heluani C S De-Lampasona M P and 26

Catalan C A N (2009) Chemistry and in Vitro Antioxidant Activity of Volatile 27

Oil and Oleoresins of Black Pepper (Piper Nigrum) J Agric Food Chem 57 5358ndash28

5364 29

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23

Karsha P V and Lakshmi O B (2010) Antibacterial activity of black pepper Piper 1

Nigrum Linn with special reference to its mode of action on bacteria Indian J 2

Nat Prod Resour 1 213-215 3

Kessler R C McGonagle K A Zhao S Nelson C B Hughes M Eshleman S 4

(1994) Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in 5

the United States Results from the National Comorbidity Survey Arch Gen 6

Psych 51 8ndash19 7

Kobayashi A Watanabe J Fukushi E Kawabata J Nakajima M and Watanabe M 8

(2003) Polyphenols from some foodstuffs as inhibitors of ovalbumin permeation 9

through caco-2 cell monolayers Biosci Biotechnol Biochem 67 1250-1257 10

Kong L D Cheng C H and Tan R X J (2004) Inhibition of MAO A and B by some 11

plant- derived alkaloids phenols and anthraquinones J Ethnopharmacol 91 351-12

355 13

Koul I B and Kapil A (1993) Evaluation of the liver protective potential of piperine 14

an active principle of black and long peppers Planta Med 59 413-417 15

Krishnakumar N Manoharan S Palaniappan P R Venkatachalam P and Manohar 16

M G (2009) Chemopreventive efficacy of piperine in 712-dimethyl benz [a] 17

anthracene (DMBA)-induced hamster buccal pouch carcinogenesis An FT-IR 18

study Food Chem Toxicol 47 2813-2820 19

Kumoro A C Singh H and Hasan M (2009) Solubility of piperine in supercritical 20

and near critical carbon dioxide J Chem Engg 17 1014-1020 21

Lambert J D Hong J Kim D H Mishin V M and Yang C S (2004) Piperine 22

enhances the bioavailability of the tea polyphenol (-)-epigallocatechin-3-gallate in 23

mice J Nutr 134 1948-1952 24

Lee C S Han E S and Kim Y K (2006) Piperine inhibition of 1-methyl-4-25

phenylpyridinium-induced mitochondrial dysfunction and cell death in PC12 26

cells Eur J Pharmacol 537 37-44 27

Lee S A Hong S S Han X H Hwang J S Oh G J Lee K S Lee M K Hwang 28

B Y and Ro J S (2005) Piperine from the fruits of Piper longum with 29

inhibitory effect on monoamine oxidase and antidepressant-like activity Chem 30

Pharm Bull 53 832ndash835 31

Page 23 of 42



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24

Lee S A Hwang J S Han X H Lee C Lee M H Choe S G Hong S S Lee D 1

Lee M K and Hwang B Y (2008) Methylpiperate derivatives from Piper 2

longum and their inhibition of monoamine oxidase Arch Pharm Res 31 679-683 3

Lee S J Umano K Shibamoto T and Lee K G (2004) Identification of volatile 4

components in basil Ocimum basilicum L and thyme leaves Thymus Vulgaris L 5

and their antioxidant properties Food Chem 91 131-137 6

Li S Wang C Wang M W Li W Matsumoto K and Tang Y Y (2007) 7

Antidepressant like effects of piperine in chronic mild stress treated mice and its 8

possible mechanisms Life Sci 80 1373-1381 9

Liao H Liu P Hu Y Wang D and Lin H (2009) Antidepressant-like effects of 10

piperine and its neuroprotective mechanism Zhongguo Zhong Yao Za Zhi 34 11

1562-1565 12

Lin Z Liao Y Venkatasamy R Hider R C and Soumyanath A (2007) Amides 13

from Piper Nigrum L with dissimilar effects on melanocyte proliferation in-vitro 14

J Pharm Pharmacol 59 529-536 15

Liston D R Nielsen J A Villalobos A Chapin D Jones S B Hubbard S T 16

Shalaby I A Ramirez A Nason D and White W F (2004) Pharmacology of 17

selective acetylcholinesterase inhibitors implications for use in Alzheimerrsquos 18

disease Eur J Pharmacol 486 9ndash17 19

Liu F and Ng T B (2000) Antioxidative and free radical scavenging activities of 20

selected medicinal herbs Life Sci 66 725ndash735 21

Liu Y Yadev V R Aggarwal B B and Nair M G (2010) Inhibitory effects of black 22

pepper (Piper Nigrum) extracts and compounds on human tumor cell 23

proliferation cyclooxygenase enzymes lipid peroxidation and nuclear 24

transcription factor-kappa-B Nat Prod Commun 5 1253-1257 25

MacKinno S Chauret D Wang M Mata R Pereda-Miranda R Jiminez A 26

Bernard C B Krishnamurty H G Poveda L J Sanchez-Vindaz P E 27

Arnason J T and Durst T (1997) Botanicals from the piperaceae and meliaceae 28

of the american neotrpoics phytochemistry Phytochemicals for pest control 29

ACS Symposium Series 658 49-57 30

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25

Majdalawieh A F Carr R I (2010) In vitro investigation of the potential 1

immunomodulatory and anti-cancer activities of black pepper (Piper Nigrum) and 2

cardamom (Elettaria cardamomum) J Med Food 13 371-381 3

Manoharan S Balakrishnan S Menon V P Alias L M and Reena A R (2009) 4

Chemopreventive efficacy of curcumin and piperine during 712-5

dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis 6

Singapore Med J 50 139-146 7

McDonnell M G and Archbold G P R (1996) Plasma ubiquinolcholesterol ratios in 8

patients with hyperlipidemia those with diabetes mellitus and in patients 9

requiring dialysis Clin Chim Acta 253 117-126 10

Mc-Mahon J B M J Currens R J Gulakowski R W J Buckheit C Lackman-Smith 11

Y F Hallock and M R Boyd (1995) Michellamine B novel plant alkaloid 12

inhibits human immunodeficiency virus-induced cell killing by at least two 13

distinct mechanisms Antimicrob Agents Chemother 39 484-488 14

McNamara F N Randall A and Gunthorpe M J (2005) Effects of piperine the 15

pungent component of black pepper at the human vanilloid receptor (TRPV1) 16

Br J Pharmacol 144 781-790 17

Mehmood M H and Gilani A H (2010) Pharmacological basis for the medicinal use 18

of black pepper and piperine in gastrointestinal disorders J Med Food 13 1086-19

1096 20

Mittal R and Gupta R L (2000) In vitro antioxidant activity of piperine Methods Find 21

Exp Clin Pharmacol 22 271-274 22

Mohandes K M and Desai D C (1999) Epidemiology of digestive tract cancer in 23

India v large and small bowel Indian J Gastroenterol 18 118-121 24

Mohit K B Mahendra B and Shrinivas K K (2009) Anti-depressant like effect of 25


induced behavioral biochemical and neurochemical changes Pharm Biochem 27

Behav 92 39-43 28

Monika M Stefanie H and Alois J (2010) Anti-inflammatory activity of extracts 29

from fruits herbs and spices Food Chem 122 987-996 30

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26

Mueller M Beck V and Jungbauer A (2011) PPARα Activation by Culinary Herbs 1

and Spices Planta Med [In press] 2

Mujumdar A M Dhuley J N DeshmukhV K Raman P H and Naik S R (1990) 3

Anti inflammatory activity of piperine Jpn J Med Biol 43 95-100 4

Murthy C T and Bhattacharya S (2008) Cryogenic grinding of black pepper J of Food 5

Eng 85 18-28 6

Musenga A Mandrioli R Ferranti A DOrazio G Fanali S and Raggi M A 7

(2007) Analysis of aromatic and terpenic constituents of pepper extracts by 8

capillary electrochromatography J Sep Sci 30 612-619 9

Nakatani N Inatani R Ohta H and Nishioka A (1986) Chemical constituents of 10

peppers piper spp and application to food preservation naturally occurring 11

antioxidative compounds Environ Health Perspect 67 135-142 12

Nalini N Sabitha K Viswanathan P and Menon V P (1998) Influence of spices on 13

the bacterial (enzyme) activity in experimental colon cancer J Ethnopharmacol 14

62 15ndash24 15

Naseri M K and Yahyavi H (2008) Antispasmodic effect of Piper Nigrum fruit hot 16

water extract on rat ileum Pak J Biol Sci 11 1492-1496 17

Nisha P Singhal R S and Pandit A B (2009) The degradation kinetics of flavor in 18

black pepper (Piper Nigrum L) J Food Eng 92 44-49 19

Okumura Y Narukawa M Iwasaki Y Ishikawa A Matsuda H Yoshikawa M 20

and Watanabe T (2010) Graduate School of Nutritional and Environmental 21

Sciences University of Shizuoka Shizouka Japan Activation of TRPV1 and 22

TRPA1 by black pepper components Biosci Biotechnol Biochem 74 68-72 23

Ononiwu I M Ibeneme C E and Ebong O O (2002) Effects of piperine on gastric 24

acid secretion in albino rats Afr J Med Med Sci 31 293-295 25

Orav A Stulova I Kailas T and Muurisepp M (2004) Effect of storage on the 26

essential oil composition of Piper Nigrum L fruits of different ripening states J 27

Agric Food Chem 52 2582-2586 28

Parmar V S Jain S C Bisht K S Jain R Taneja P Jha A Tyagi O D Prasad A 29

K Wengel J Olsen C E and Boll P M (1997) Phytochemistry of the genus 30

piper Photochemistry 46 597-673 31

Page 26 of 42



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Only

27

Pattanaik S Hota D Prabhakar S Kharbanda P and Pandhi P (2009) 1

Pharmacokinetic Interaction of Single Dose of Piperine with Steady-state 2

Carbamazepine in Epilepsy Patients Phytother Res 23 1281ndash1286 3

Pattanaik S Hota D Prabhakar S Kharbanda P and Pandhi P (2006) Effect of 4

piperine on the steady-state pharmacokinetics of phenytoin in patients with 5

epilepsy Phytother Res 20 683-686 6

Platel K Rao A Saraswathi G and Srinivasan K (2003) Digestive stimulant action 7

of three indian spices mixes in experimental rats Nahrung 46 394-398 8

Politeo O Jukic M and Milos M (2006) Chemical composition and antioxidant 9

activity of essential oils of twelve spice plants Croat Chem Acta 79 545-552 10

Polovka M and Suhaj M (2010) The effect of irradiation and heat treatment on 11

composition and antioxidant properties of culinary herbs and spices A Review 12

Food Rev Int 26 138-161 13

Prakash U N and Srinivasan K (2010) Gastrointestinal protective effect of dietary 14

spices during ethanol-induced oxidant stress in experimental rats Appl Physiol 15

Nutr Metab 35 134-141 16

Ramasamy S V Namasivayam N (2006) Efficacy of piperine an alkaloidal 17

constituent from Piper Nigrum on erythrocyte antioxidant status in high fat diet 18

and antithyroid drug induced hyperlipidemic rats Cell Biochem Func 24 491-19

498 20

Rauscher F M Sanders R A and Watkins J B (2007) Effects of piperine on 21

antioxidant pathways in tissues from normal and streptozotocin-induced 22

diabetic rats J Biochem Mol Toxicol 14 329-334 23

Reen R K Wiebel F J Singh J (1997) Piperine inhibits aflatoxin B1-induced 24

cytotoxicity and genotoxicity in V79 Chinese hamster cells genetically engineered 25

to express rat cytochrome P4502B1 J Ethnopharmacol 58 165-173 26

Renjie L Shidi S and Yongjun M (2010) Analysis of volatile oil composition of the 27

peppers from different production areas Med Chem Res 19 157-165 28

Sabina E P Nagar S and Rasool M (2011) A Role of Piperine on Monosodium Urate 29

Crystal-Induced Inflammation-An Experimental Model of Gouty Arthritis 30

Inflammation [In Press] 31

Page 27 of 42



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For Peer Review

Only

28

Sangwan P L Koul J L Koul S Reddy M V Thota N Khan I A Kumar A 1

Kalia N P and Qazi G N (2008) Piperine analogs as potent Staphylococcus 2

aureus NorA efflux pump inhibitors Bioorg Med Chem 16 9847-9857 3

Saraswat M Muthenna P Suryanarayana P Petrash J M and Reddy G B (2008) 4

Dietary sources of aldose reductase inhibitors prospects for alleviating diabetic 5

complications Asia Pac J Clin Nutr 17 558-565 6

Saraswat M Reddy P Y Muthenna P and Reddy G B (2009) Prevention of non-7

enzymic glycation of proteins by dietary agents prospects for alleviating diabetic 8

complications Br J Nutr 101 1714-1721 9

Saxena R Venkaiah K Anitha P Venu L and Raghunath M (2007) Antioxidant 10

activity of commonly consumed plant foods of India contribution of their 11

phenolic content Int J Food Sci Nutr 58 250-260 12

Schecter A Birnbaum L Ryan J J and Constable J D (2006) Dioxins an overview 13

Environ Res 101 419-428 14

Scott I M Puniani E Durst T Phelps D Merali S Assabgui R A Sanchez-15

Vindas P Poveda l Philgene B J R and Arnason J T (2002) Insecticidal 16

activity of piper tuberculatum extract synergistic interaction of piperamides 17

Agric Forest Entamol 4 137-144 18

Seifried H E Anderson D E Fisher E I and Milner J A (2007) A review of the 19

interaction among dietary antioxidants and reactive oxygen species J Nut 20

Biochem 18 567-579 21

Selvendiran K and Sakthisekaran D (2004) Chemopreventive effect of piperine on 22

modulating lipid peroxidation and membrane bound enzymes in benzo(a)pyrene 23

induced lung carcinogenesis Biomed Pharmacother 58 264-267 24

Selvendiran K Mumtaz Banu S Sakthisekaran D (2004) Protective effect of piperine 25

on benzo [a] pyrene-induced lung carcinogenesis in Swiss albino mice Clin 26

Chim Acta 350 73ndash78 27

Selvendiran K Singh J P and Sakthisekaran D (2006) In vivo effect of piperine on 28

serum and tissue glycoprotein levels in benzo [a] pyrene induced lung 29

carcinogenesis in Swiss albino mice Pulm Pharmacol Ther 19 107ndash111 30

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For Peer Review

Only

29

Selvendiran K Singh J P Krishnan K B and Sakthisekaran D (2003) 1

Cytoprotective effect of piperine against benzo[a]pyrene induced lung cancer 2

with reference to lipid peroxidation and antioxidant system in swiss albino mice 3

Fitoterapia 74 109-115 4

Selvendiran K Thirunavukkarasu C Singh J P Padmavathi R and Sakthisekaran 5

D (2005) Chemopreventive effect of piperine on mitochondrial TCA cycle and 6

phase-i and glutathione-metabolizing enzymes in benzoapyrene induced lung 7

carcinogenesis in swiss albino mice Mol Cell Biochem 271 101-116 8

Shaikh J Bhosale R and Singhal R (2006) Microencapsulation of black pepper 9

oleoresin Food Chem 94 105-110 10

Shankaracharya N B Rao L J Naik J P and Nagalakshmi S (1997) 11

Characterisation of chemical constituents of indian long pepper Piper Longum L 12

J Food Sci Technol Mysore 34 73-75 13

Singh G Marimuthu P Murali H S Bawa A S (2005) Antioxidative and 14

antibacterial potentials of essential oils and extracts isolated from various spice 15

materials J Food Safety 25 130ndash145 16

Singletary K (2010) Black Pepper Overview of health benefits Food Sci 45 43-47 17

Sloan A E (2005) Top 10 global food trends Food Technol 59 20ndash32 18

Snyman T Stewart M J and Steenkamp V (2001) A fatal case of pepper poisoning 19

Forensic Sci Int 124 43-46 20

Soumyanath A Venkatasamy R Joshi M Faas L Adejuyigbe B Drake A Hider 21

R C and Young A R (2006) UV Irradiation affects melanocyte stimulatory 22

activity and protein binding of piperine Photochem Photobiol 82 1541-1548 23

Sowbhagya H B Sampathu S R Krishnamurthy N and Shankaranarayana M L 24

(1990) Stability of piperine in different solvents and its spectrophotometric 25

estimation Ind Spices 27 21-23 26

Srinivasan K (2005a) Role of Spices beyond food flavouring nutraceuticals with 27

multiple health effects Food Rev Int 21 167-188 28

Srinivasan K (2005b) Spices as influencers of body metabolism an overview of three 29

decades of research Food Res Int 38 77-86 30

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For Peer Review

Only

30

Srinivasan K (2007) Black pepper and its pungent principle-piperine a review of 1

diverse physiological effects Crit Rev Food Sci Nutr 47 735-748 2

Srinivasan K (2008) Reason to Season Spices as functional food adjuncts with multiple 3

health effects Ind Food Indus 27 36-47 4

Srinivasan K Sambaiah K and Chandrasekhara N (2004) Spices as beneficial 5

hypolipidemic food adjuncts A Review Food Rev Int 20 187-220 6

Stohr J R Xiao P G and Bauer R (2001) Constituents of Chinese Piper species and 7

their inhibitory activity on prostaglandin and leukotriene biosynthesis in vitro J 8

Ethnopharmacol 75 133-139 9

Su L Yin J J Charles D Zhou K Moore J and Yu L (2007) Total phenolic 10

contents chelating capacities and radical-scavenging properties of black 11

peppercorn nutmeg rosehip cinnamon and oregano leaf Food Chem 100 990-12

997 13

Suresh D and Srinivasan K (2007) Studies on the in vitro absorption of spice 14

principles--curcumin capsaicin and piperine in rat intestines Food Chem Toxicol 15

45 1437-1442 16

Suresh D and Srinivasan K (2010) Tissue distribution amp elimination of capsaicin 17

piperine amp curcumin following oral intake in rats Ind J Med Res 131 682-691 18

Suresh D Srinivasan K (2006) Influence of curcumin capsaicin and piperine on the 19

rat liver drug-metabolizing enzyme system in vivo and in vitro Can J Physiol 20

Pharmacol 84 1259-1265 21

Szallasi A (2005) Piperine Researchers Discover New Flavor in an Ancient Spice 22

Trends Pharmacol Sci 26 437-439 23

Tachakittirungrod S Okonogi S and Chowwanapoonpoh S (2007) Study on 24

antioxidant activity of certain plants in thailand mechanism of antioxidant 25

action of guava leaf extract Food Chem 103 381-388 26

Taqvi S I Shah A J and Gilani A H (2008) Blood pressure lowering and 27

vasomodulator effects of piperine J Cardiovasc Pharmacol 52 452-458 28

Thanuja T V Hedge R V Sreenivasa M N (2002) Induction of rooting and root 29

growth in black pepper cuttings (Piper Nigrum L) with inoculation of arbuscular 30

mycorrhizae Sci Hort 92 339-346 31

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For Peer Review

Only

31

Thirunavukkarasu C Singh J P V Selvendiran K and Sakthisekaran D (2001) 1

Chemopreventive efficacy of selenium against N-nitrosodiethylamine-induced 2

hepatoma in albino rats Cell Biochem Funct 19 265-271 3

Tipsrisukond N Fernando L N and Clarke A D (1998) Antioxidant effects of 4

essential oil and oleoresin of black pepper from supercritical carbon dioxide 5

extractions in ground pork J Agric Food Chem 46 4329-4333 6

Utpala P Asish G R Zachariah T J Saji K V Johnson K G and Mathew P A 7

(2008b) Spatial influence on the important biochemical properties of Piper 8

Nigrum linn leaves Nat Prod Radiance 7 444-447 9

Vellaichamy L Balakrishnan S Panjamurthy K Manoharan S Alias L M (2009) 10

Chemopreventive potential of piperine in 712-dimethylbenz[a]anthracene 11

induced skin carcinogenesis in Swiss albino mice Environ Toxicol Pharmacol 28 12

11ndash18 13

Venkatasamy R Faas L Young A R Raman A and Hider R C (2004) Effects of 14

piperine analogues on stimulation of melanocytes proliferation and melanocyte 15

differentiation Bioorganic Med Chem 12 1905ndash1920 16

Vijayakumar R S and Nalini N (2006) Efficacy of piperine an alkaloidal constituent 17

from Piper Nigrum on erythrocyte antioxidant status in high fat diet and 18

antithyroid drug induced hyperlipidemic rats Cell Biochem Function 24 491ndash498 19

Vijayakumar R S Surya D and Nalini N (2004) Antioxidant efficacy of black 20

pepper (Piper Nigrum L ) and piperine in rats with high fat diet induced 21

oxidative stress Redox Rep 9 105-110 22

Volak L P Ghirmai S Cashman J R and Court M H (2008) Curcuminoids inhibit 23

multiple human cytochromes P450 UDP-glucuronosyltransferase and 24

sulfotransferase enzymes whereas piperine is a relatively selective CYP3A4 25

inhibitor Drug Metab Dispos 36 1594-1605 26

Wattanathorn J Chonpathompikunlert P Muchimapura S Priprem A and 27

Tankamnerdthai O (2008) Piperine the potential functional food for mood and 28

cognitive disorders Food Chem Toxicol 46 3106-3110 29

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For Peer Review

Only

32

Weerakkody N S Caffin N Turner M S and Dykes G A (2010) In vitro 1

antimicrobial activity of less-utilized spice and herb extracts against selected 2

food-borne bacteria Food Control 21 1408-1414 3

Wood A B Barrow M L and James D J (1988) Piperine determination in pepper 4

Piper Nigrum L and its oleoresins A reversed phase high performance liquid 5

chromatographic method J Flavour Frag 3 55-64 6

Yadav A S and Bhatnagar D (2007) Modulatory effect of spice extracts on iron-7

induced lipid peroxidation in rat liver Biofactors 29 147-157 8

Youdim K A Spencer J P Schroeter H and Rice-Evans C (2002) Dietary 9

flavonoids as potential neuroprotectants Biol Chem 383 503ndash519 10

Zachariah T J and Parthasarathy V A (2008) Black pepper In Chemistry of Spices 11

pp 21-40 Parthasarathy V A Chempakam B and Zachariah T J Eds CABI 12

UK 13

Zachariah T J Safeer A L Jayarajan K Leela N K Vipin T M Saji K V Shiva K 14

N Parthasarathy V A and Mammootty K P (2010) Correlation of 15

metabolites in the leaf and berries of selected black pepper varieties Sci Horti 16

123 418-422 17

Zarotsky V Sramek J J and Cutler N R (2003) Galantamine hydrobromide an 18

agent for Alzheimerrsquos disease Am J Health Syst Pharm 60 446ndash452 19

Zhou S Gao Y Jiang W Huang M Xu A and Paxton J W (2003) Interactions of 20

herbs with cytochrome Drug Metab Rev 35 35ndash98 21

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nly

Table-1 Botanical Classification of black pepper Groups Name

Kingdom Plantae

Subkingdom Tracheobionta

Superdivision Spermatophyta

Division Magnoliophyta

Class Magnoliopsida

Subclass Magnoliidae

Family Piperales

Order Piperaceae

Genus Piper L

Specie Piper nigrum L Source USDA NRCS 2010 The PLANTS Database (httpplants usdagov 9 May 2010)

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Table 2 Rich phytochemistry of the black pepper Sr No Researcher Chemical Components Percentage

1 Lee et al (2004) Singletary (2010)

Essential oil Piperine Chavicine Piperidine Fatty oils Resin Starch

1-25 5-9 1 8 6-8 0-5 22-42

2 Ravindran and Johny (2001)

Essential oil Piperine Starch Oleoresin

04 to 70 20 to 74 15-45 35-12

3 Murthy and Bhattacharya (2008)

Essential oil (limonene β-caryophyllene sabinene and β-pinene)

4 Singh et al (2005) Acetone extract Piperine Piperolein Piper amide Guineensine

335 137 34 323

5 Utpala et al (2008) Phenol contents 03 to 08 mgg

6 Orav et al (2004) Musenga et al (2007)

Essential oil

β-caryophyllene Limonene β-pinene ∆-3-carene Sabinene α-pinene Eugenol Terpinen-4-ol Hedycaryol β-eudesmol Caryophyllene oxide α-phellandrene

14-704 29-384 07-256 17-190 0-122 03-104 01-410 0-132 0-91 0-97 01-72 NA

7 Jirovetz et al (2002) Elemol Germacrene-D Limonene Β-pinene α-pinene β-ocimine β-pinene α-phellandrene αhumulene ∆-carene Βphellandrene T-muurolol

Page 34 of 42



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Table 3 Functional amp Nutraceuticals Effect of Bioactive Compounds of Black Pepper

Bioactive compounds

Functional amp Nutraceuticals Role Researchers

Piperine

1 Bio-absorption of vitamins and trace elements 2 Effective against acute inflammatory process 3 Antimicrobial properties 4 Improved functionality of gastrointestinal tract 5 Decreased body weight and visceral fat accumulation 6 Improved bioavailability of curcumin and catechins 7 Enhanced bioavailability of many drugs 8 Piperine ameliorate the chronic mild stress 9 Reduce risk of cancer 10 reducing the extent of toxicity of certain components

Kumoro et al 2009 Capasso et al 2002 Bang et al 2009 Sangwan et al 2008 Badmaev et al 2000 Okumura et al 2010 Singletary 2010 Pattanaik et al 2009 Li et al 2007 Vellaichamy et al 2009 Han et al 2008

Essential oil

1 Contributes aroma 2 Control worm infestations

Zachariah et al 2010 Dorman and Deans 2000

Phenolics 1 Reduce oxidation process 2 Ameliorating oxidative stress

Renjie et al 2010 Saxena et al 2007

Page 35 of 42



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Journal Critical Reviews in Food Science and Nutrition Manuscript ID BFSN-2011-0286 Manuscript Title BLACK PEPPER AND HEALTH CLAIMS A COMPREHENSIVE

TREATISE

Dear Editor I have seen the reviewerrsquos comments eagerly and made the following changes in the article as per desired Query 1 The some text in the article should be written again as language should be

simple and lucid for the readers and researchers The use of same

sentencesconcepts aspects at multiple places should be avoided

Answer 1 Corrections have been made Now appropriate words are used for

specific purpose

Query 2 Health benefits should be checked again and each aspect should be

discussed only at one place I would suggest the authors to add up one or

two table regarding the health promoting potential of the black pepper

Answer 2 Every aspect related to health endorsing effects of black pepper has been

discussed separately only at one place Table regarding health benefits of

black pepper has now been added in the manuscript

Query 3 Finally yet importantly grammatical errors should be removed

Answer 3 All grammatical errors have been eliminated from the text

Query 4 The first line of the abstract should be as ldquoFor millennia spices have been

an integral part of human diets and commerce Recently the widespread

recognition of diet-health linkages bolsters the dietary importance of

spices and herbsrdquo

Answer 4 It has been changed according to reviewerrsquos comments

Query 5 The words selection should be appropriate especially in the abstract

section eg ldquoholdrdquo is used twice that should be avoided

Answer 5 Proper and suitable words has been incorporated in text especially

abstract portion and duplication has been removed

Page 36 of 42



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Query 6 Page 1 Line 24 The sentence use should ldquoBlack pepper (Piper nigrum L)

is an important healthy food owing to its antioxidant amp antimicrobial

potential and gastro-protective modulesrdquo

Answer 6 Now sentence is according to reviewerrsquos suggestions

Query 7 From abstract ldquoMore recently cell-culture studies and animal modeling

predicted the role of black pepper against number of maladiesrdquo can be

omitted as its duplication of same concepts mentioned earlier

Answer 7 We all authors have discussed and suggested that this sentence has

different meanings and not considered as duplication

Query 8 Page 1 Line 37 Component should be replaced with components in the

abstract Accordingly the complete sentence should be re-written

Answer 8 The word ldquocomponentsrdquo has remained same as it means different

components of piper nigrum

Query 9 Meta-analysis represents single expression or experiment so it should be

changed to meta-analyses

Answer 9 Changes has been incorporated according to reviewerrsquos comments

Query 10 First and second paragraph can be combined into one I think following

could be one possibility ldquoIn the recent era efforts have been directed to

establish scientific rationale for health improving potential of functional

and nutraceuticals foods Amongst prevention of cardiovascular

disorders (CVD) cancer insurgence diabetes mellitus Alzheimerrsquos

disease and variety of inflammatory ailments through dietary modules is

of prime consideration Moreover emerging findings in the nutrigenomics

and proteomics further reflected their importance in a deeper sense

(Chonpathompikunlert et al 2010) The list of healthy foods marketed

with distinct health claims is long enough However spices and their

bioactive components are more promising candidates for their inclusion in

diet-based regimens to improve human health (Geoffrey 2006 Butt et al

2009) Their different parts including dried seed bark fruit root and

Page 37 of 42



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For Peer Review O

nly

flower are in use as food adjuncts that impart flavor aroma and color to

foods (Srinivasan 2008 Singletary 2010)rdquo

Answer 10 First and second paragraph of manuscript has now been combined

Query 11 Chonpathompikunlert et al 2010 should be checked again Is paper

published in 2010 or 2009 as two references are given in reference section

Answer 11 Chonpathompikunlert et al 2010 has been published in 2010

Query 12 Why authors written these sentence eg ldquoBeing the sole reason for many

of the attacks in the ancient ages still considered instrumental in the

economies of many nations across the globe (Srinivasan 2005)rdquo and

ldquoDuring the era of industrialization and globalization these commodities

were traded in the western countries that led to wide bloom in their

productionrdquo as they must be deleted I would suggest authors to look into

introduction again and reduce its length to 34th Moreover the sentences

should be linked with each in the same paragraphs

Answer 12 The Correction has been and these sentences were deleted from the text

Query 13 Page 3 Line 1 Human subject should be replaced with human subjects

Answer 13 It has been done according to suggestions

Query 14 The last two paragraphs can also be merged up into one

Answer 14 Both paragraphs has been combined

Query 15 Functional uses can be replaced with applications

Answer 15 Changes has been incorporated according to comment

Query 16 The first paragraph should be re-written again Last sentence can be

deleted The authors should delete the reference ldquoDM 2009rdquo

Answer 16 Changes have been made in first paragraph Reference has also been

deleted

Query 17 The authors should be specific is use of unit systems as molminus1 is not right

as it should be molminus1 Please check the manuscript again

Answer 17 Unit has been written properly All manuscript has now been carefully

written

Page 38 of 42



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For Peer Review O

nly

Query 18 ldquoPiperine and its allied components like piperidine and chavicine are

responsible for pungent properties of black pepper (Badmaev et al 2000

Bhattacharjee and Sengupta 2009)rdquo should be adjusted at the end of first

paragraph of heading ldquopiperinerdquo

Answer 18 Correction has been made accordingly

Query 19 Page 6 Line 17 ldquoBlack pepper essential oil contributes towards the aroma

oleoresin contributes towards the overall taste and the alkaloid piperine

imparts pungency (Zachariah et al 2010)rdquo should be adjusted in the first

paragraph of the main heading

Answer 19 All has been incorporated according to reviewerrsquos suggestion

Query 20 The section of essential oil amp phenolics should be re-written

Answer 20 This portion has now been re-written again

Query 21 The introduction of each aspectsub-heading should be deleted It will

reduce the length of the article considerably The same point is valid for

some other parts of the manuscript too eg Page 7 (Line 13-19) Page 10

(Line 4-10) Page 14 Line 7-21) Page 18 (Line 28-30) etc The text should

be reduced in all these cases

Answer 21 All sub headings has been deleted from the text

Query 22 Humanity should be replaced with mankind as humanity is property not

noun

Answer 22 Humanity has now been replaced with mankind

Query 23 ldquousing different assays ie thiobarbituric acid value (TBA) DPPH radical

scavenging and total antioxidant activity (FTC method)rdquo can be deleted

Answer 23 It has been done according to reviewerrsquos comments

Query 24 ldquoIn addition the inhibitory action as observed through FTC method

strengthened the claims for strong antioxidant activities of essential oil

and oleoresinsrdquo can also be deleted


Query 25 Page 8 Line 18 Paragraph needs re-phrasing to make it lucid

Page 39 of 42



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For Peer Review O

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Answer 25 Paragraph has been re-phrased

Query 26 ldquoSpices and herbs are traditional remedies to cure some maladies and

diseased conditions in South Asian territoriesrdquo is duplication thus should

be removed

Answer 26 All duplicate sentences have been removed from the text

Query 27 Re-arrange the section ldquoAnti-inflammatory Potentialrdquo to make it lucid and

introductory details should be avoided eg ldquoThey postulated that

inhibition of interlukon (IL6) matrix metalloproteinase (MMPs)

prostaglandin E2 (PGE2) and activator protein 1rdquo need further clarity

Answer 27 The paragraph has been re-arranged and cleared completely

Query 28 C Antimicrobial Potential of Black Pepper Reference support is limited

Answer 28 More references has now been added in this portion

Query 29 Gastrointestinal health and nutrient absorption needs revision in first and

last paragraph to clear the evidences presented

Answer 29 The literature regarding gastrointestinal health and nutrient absorption

has been revised properly

Query 30 Page 13 Line 5-21 Can data be presented in Tabular form

Answer 30 The details are mentioned in the text Therefore its tabular presentation

would be only duplication of findings not else

Query 31 ldquoSeveral research interventions resulted in finalizing the assumption that

the depressed state is result of many factors that act into play of which

patho-physiological changes of depression includes the increased

glucocorticoid secretion followed by decreased level of brain derived

neurotrophic factor in the hippocampusrdquo can be deleted

Answer 31 The section has been deletec

Query 32 ldquoThe combination of all these parameters can lead to the state where

reduction of hippocampal volume occurs thus resulting in depression and

allied discrepanciesrdquo can also be deleted


Page 40 of 42



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For Peer Review O

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Query 33 ldquoChronic stress procedure (CSP) induction in rats is suitable model used

worldwide to assess the potential of dietary components and drugs

against depressionrdquo can also be deleted


Query 34 ldquoThe efficacy of drugs is limited as they are effective in the initial stages

but unable to stop the cascade of events going on the central nervous

systemrdquo can not be claimed as most of ailments are treated with the

pharmaceuticals

Answer 34 The section has been deleted and suggestion has been incorporated

Query 35 Last paragraph at Page 15 should be re-written

Answer 35 The last paragraph has been skipped as it was carrying information

supported by only one or two references

Query 36 First paragraph at ldquoBlack pepper against cancerrdquo should be revised

Answer 36 The paragraph is revised and its now writes as ldquoAccording to an estimate

the prevalence of cancer can be reduced (30 to 40) with the dietary habits

(Anto et al 2002 Zhou et al 2003) Some population-based studies also

indicated that consumption of foods rich in bioactive molecules can

decrease the risk of various ailments especially cancer In this regard

consumption of spices is positively correlated with reduced risks of cancer

incidence in Asian and Mediterranean regions (Mohandes et al 1999)

Even the higher risk of malignancies in developing economies can be

linked with the reduced intake of spices (Fleischauer et al 2000 Sloan

2005 Selvendiran et al 2005)rdquo

Query 37 The citations like ldquoZhou et al (2003)rdquo Vellaichamy et al (2009) and

Krishnakumar et al (2009) needs little elaboration regarding their findings

and mechanisms of action Its looks only addition of references as their

results is not properly elaborated

Answer 37 The results of researchers suggested above are mentioned in the text

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Query 38 The section ldquoOther Health Benefitsrdquo needs some greater considerations as

authors just piled up information and literature rather made conclusive

discussion The section can be completely omitted However if authors

want to retain the text than a Tablefigure can be more useful

Answer 38 The section is reviewed again and duplications and unnecessary details

are now skipped from the text

Query 39 Paragraph starting from Vanilloid receptor (TRPV1) should be completely

omitted ass its just contains three studies and no clear links are discussed

with special reference to nutrition point of view

Answer 39 The complete paragraph has been deleted

Query 40 In my view ldquoSome other studies are also available regarding health

promoting potentials of black pepper However many of them are limited

in their applications owing to lack of animal studiesrdquo should be added at

the end of heading ldquoOther health benefitsrdquo

Answer 40 The answer is same as to mentioned in Suggestion 35

Query 41 Authors should check references section again for style and etc Some

references needs to be cited in the text and vice versa

Answer 41 The references style has been checked again and mistakes observed are

corrected

I would like accept that mistakes removed from the article considerably and indeed I am looking forward for better write-up and presentation skills in the future Lastly I would like to request to kindly accept the manuscript as it has been considerably improved Corresponding authors M Tauseef Sultan Assistant Professor Bahauddin Zakariya University Multan Email tauseefsultanhotmailcom

Page 42 of 42



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1

TYPE OF ARTICLE Review article 1

TITLE BLACK PEPPER AND HEALTH CLAIMS A COMPREHENSIVE 2

TREATISE 3

4

5

1 Masood Sadiq Butt 6



9

2 Imran Pasha 10



13

3 Muhammad Tauseef Sultan 14


Bahauddin Zakariya University Multan 16

17

4 M Atif Randhawa 18



21

5 Farhan Saeed 22



25

6 Waqas Ahmad 26



29

30

daggerCorresponding author 31

Dr Muhammad Tauseef Sultan 32


Bahauddin Zakariya University 34

Multan Pakistan 35

Contact No 0092-333-9949100 36

Email tauseefsultanhotmailcom 37

Page 1 of 42



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2




ABSTRACT























various ailments


Page 2 of 42



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3

I Introduction 1































Page 3 of 42



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4





























A Piperine 29



Page 4 of 42



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5







1997) 7



















B Essential oil 26






Page 5 of 42



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6
































Page 6 of 42



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7









2000) 9























Page 7 of 42



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8
































Page 8 of 42



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9
































Page 9 of 42



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10
































Page 10 of 42



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11
































Page 11 of 42



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12
































Page 12 of 42



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Only

13





























et al 2009) 29



Page 13 of 42



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Only

14
































Page 14 of 42



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15
































Page 15 of 42



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16



Carr 2010) 3













perspectives 16















Page 16 of 42



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17























Conclusion 23









Page 17 of 42



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18





References 5






663 11






Bull 26 1754-1760 17




23 143-150 21




Agents 12 257-262 25







Page 18 of 42



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19















Behav 92 39-43 15















Page 19 of 42



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20









Food 11 275-281 9













Biophys 464 269-276 22









Page 20 of 42



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21


50 18ndash23 2



1047-1052 5








66 13










283-289 23








Bao 7 667-70 31

Page 21 of 42



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22













Med 5 257-262 13



23 1194-1196 16





265-275 21




Pharmacol 43 1401-1407 25




5364 29

Page 22 of 42



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23







Psych 51 8ndash19 7






355 13











mice J Nutr 134 1948-1952 24








Page 23 of 42



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24












1562-1565 12



















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25




















1096 20








Behav 92 39-43 28



Page 25 of 42



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26






Eng 85 18-28 6









62 15ndash24 15

















Page 26 of 42



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27













Food Rev Int 26 138-161 13



Nutr Metab 35 134-141 16




498 20












Page 27 of 42



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28














Environ Res 101 419-428 14







Biochem 18 567-579 21










Page 28 of 42



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29































Page 29 of 42



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30













997 13



45 1437-1442 16





Pharmacol 84 1259-1265 21











Page 30 of 42



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31













11ndash18 13

















Page 31 of 42



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32













UK 13




123 418-422 17





Page 32 of 42



123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

For Peer Review O

nly


Kingdom Plantae




Class Magnoliopsida


Family Piperales

Order Piperaceae

Genus Piper L


Page 33 of 42



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For Peer Review O

nly




1-25 5-9 1 8 6-8 0-5 22-42



04 to 70 20 to 74 15-45 35-12




335 137 34 323



Essential oil


14-704 29-384 07-256 17-190 0-122 03-104 01-410 0-132 0-91 0-97 01-72 NA


Page 34 of 42



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nly


Bioactive compounds


Piperine



Essential oil





Page 35 of 42



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TREATISE





specific purpose


















Page 36 of 42



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nly






























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nly

























deleted




written

Page 38 of 42



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nly




















noun










Page 39 of 42



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For Peer Review O

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be removed


























Page 40 of 42



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For Peer Review O

nly








pharmaceuticals





















Page 41 of 42



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corrected


Page 42 of 42



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2




ABSTRACT























various ailments


Page 2 of 42



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3

I Introduction 1































Page 3 of 42



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4





























A Piperine 29



Page 4 of 42



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5







1997) 7



















B Essential oil 26






Page 5 of 42



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6
































Page 6 of 42



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7









2000) 9























Page 7 of 42



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8
































Page 8 of 42



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9
































Page 9 of 42



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10
































Page 10 of 42



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11
































Page 11 of 42



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12
































Page 12 of 42



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13





























et al 2009) 29



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14
































Page 14 of 42



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15
































Page 15 of 42



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16



Carr 2010) 3













perspectives 16















Page 16 of 42



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17























Conclusion 23









Page 17 of 42



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18





References 5






663 11






Bull 26 1754-1760 17




23 143-150 21




Agents 12 257-262 25







Page 18 of 42



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19















Behav 92 39-43 15















Page 19 of 42



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20









Food 11 275-281 9













Biophys 464 269-276 22









Page 20 of 42



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21


50 18ndash23 2



1047-1052 5








66 13










283-289 23








Bao 7 667-70 31

Page 21 of 42



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22













Med 5 257-262 13



23 1194-1196 16





265-275 21




Pharmacol 43 1401-1407 25




5364 29

Page 22 of 42



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23







Psych 51 8ndash19 7






355 13











mice J Nutr 134 1948-1952 24








Page 23 of 42



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24












1562-1565 12



















Page 24 of 42



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25




















1096 20








Behav 92 39-43 28



Page 25 of 42



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26






Eng 85 18-28 6









62 15ndash24 15

















Page 26 of 42



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27













Food Rev Int 26 138-161 13



Nutr Metab 35 134-141 16




498 20












Page 27 of 42



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28














Environ Res 101 419-428 14







Biochem 18 567-579 21










Page 28 of 42



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29































Page 29 of 42



123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

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30













997 13



45 1437-1442 16





Pharmacol 84 1259-1265 21











Page 30 of 42



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31













11ndash18 13

















Page 31 of 42



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32













UK 13




123 418-422 17





Page 32 of 42



123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

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nly


Kingdom Plantae




Class Magnoliopsida


Family Piperales

Order Piperaceae

Genus Piper L


Page 33 of 42



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For Peer Review O

nly




1-25 5-9 1 8 6-8 0-5 22-42



04 to 70 20 to 74 15-45 35-12




335 137 34 323



Essential oil


14-704 29-384 07-256 17-190 0-122 03-104 01-410 0-132 0-91 0-97 01-72 NA


Page 34 of 42



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nly


Bioactive compounds


Piperine



Essential oil





Page 35 of 42



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nly


TREATISE





specific purpose


















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nly

























deleted




written

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noun










Page 39 of 42



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be removed


























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pharmaceuticals





















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corrected


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I Introduction 1































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A Piperine 29



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1997) 7



















B Essential oil 26






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2000) 9























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et al 2009) 29



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Carr 2010) 3













perspectives 16















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Conclusion 23









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References 5






663 11






Bull 26 1754-1760 17




23 143-150 21




Agents 12 257-262 25







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Food 11 275-281 9













Biophys 464 269-276 22









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50 18ndash23 2



1047-1052 5








66 13










283-289 23








Bao 7 667-70 31

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Med 5 257-262 13



23 1194-1196 16





265-275 21




Pharmacol 43 1401-1407 25




5364 29

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Psych 51 8ndash19 7






355 13











mice J Nutr 134 1948-1952 24








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1562-1565 12



















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Behav 92 39-43 28



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Eng 85 18-28 6









62 15ndash24 15

















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Food Rev Int 26 138-161 13



Nutr Metab 35 134-141 16




498 20












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Environ Res 101 419-428 14







Biochem 18 567-579 21










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997 13



45 1437-1442 16





Pharmacol 84 1259-1265 21











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11ndash18 13

















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UK 13




123 418-422 17





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Kingdom Plantae




Class Magnoliopsida


Family Piperales

Order Piperaceae

Genus Piper L


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1-25 5-9 1 8 6-8 0-5 22-42



04 to 70 20 to 74 15-45 35-12




335 137 34 323



Essential oil


14-704 29-384 07-256 17-190 0-122 03-104 01-410 0-132 0-91 0-97 01-72 NA


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Bioactive compounds


Piperine



Essential oil





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TREATISE





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pharmaceuticals





















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A Piperine 29



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1997) 7



















B Essential oil 26






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2000) 9























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et al 2009) 29



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Carr 2010) 3













perspectives 16















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Conclusion 23









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References 5






663 11






Bull 26 1754-1760 17




23 143-150 21




Agents 12 257-262 25







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Food 11 275-281 9













Biophys 464 269-276 22









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50 18ndash23 2



1047-1052 5








66 13










283-289 23








Bao 7 667-70 31

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Med 5 257-262 13



23 1194-1196 16





265-275 21




Pharmacol 43 1401-1407 25




5364 29

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Psych 51 8ndash19 7






355 13











mice J Nutr 134 1948-1952 24








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1562-1565 12



















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1096 20








Behav 92 39-43 28



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Eng 85 18-28 6









62 15ndash24 15

















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Food Rev Int 26 138-161 13



Nutr Metab 35 134-141 16




498 20












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Environ Res 101 419-428 14







Biochem 18 567-579 21










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997 13



45 1437-1442 16





Pharmacol 84 1259-1265 21











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11ndash18 13

















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UK 13




123 418-422 17





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Kingdom Plantae




Class Magnoliopsida


Family Piperales

Order Piperaceae

Genus Piper L


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1-25 5-9 1 8 6-8 0-5 22-42



04 to 70 20 to 74 15-45 35-12




335 137 34 323



Essential oil


14-704 29-384 07-256 17-190 0-122 03-104 01-410 0-132 0-91 0-97 01-72 NA


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Bioactive compounds


Piperine



Essential oil





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specific purpose


















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pharmaceuticals





















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1997) 7



















B Essential oil 26






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2000) 9























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et al 2009) 29



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Carr 2010) 3













perspectives 16















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Conclusion 23









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References 5






663 11






Bull 26 1754-1760 17




23 143-150 21




Agents 12 257-262 25







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Food 11 275-281 9













Biophys 464 269-276 22









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50 18ndash23 2



1047-1052 5








66 13










283-289 23








Bao 7 667-70 31

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Med 5 257-262 13



23 1194-1196 16





265-275 21




Pharmacol 43 1401-1407 25




5364 29

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Psych 51 8ndash19 7






355 13











mice J Nutr 134 1948-1952 24








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1562-1565 12



















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Behav 92 39-43 28



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Eng 85 18-28 6









62 15ndash24 15

















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Food Rev Int 26 138-161 13



Nutr Metab 35 134-141 16




498 20












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Environ Res 101 419-428 14







Biochem 18 567-579 21










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997 13



45 1437-1442 16





Pharmacol 84 1259-1265 21











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UK 13




123 418-422 17





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Kingdom Plantae




Class Magnoliopsida


Family Piperales

Order Piperaceae

Genus Piper L


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1-25 5-9 1 8 6-8 0-5 22-42



04 to 70 20 to 74 15-45 35-12




335 137 34 323



Essential oil


14-704 29-384 07-256 17-190 0-122 03-104 01-410 0-132 0-91 0-97 01-72 NA


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Bioactive compounds


Piperine



Essential oil





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2000) 9























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et al 2009) 29



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Carr 2010) 3













perspectives 16















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Conclusion 23









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References 5






663 11






Bull 26 1754-1760 17




23 143-150 21




Agents 12 257-262 25







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Food 11 275-281 9













Biophys 464 269-276 22









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50 18ndash23 2



1047-1052 5








66 13










283-289 23








Bao 7 667-70 31

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Med 5 257-262 13



23 1194-1196 16





265-275 21




Pharmacol 43 1401-1407 25




5364 29

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Psych 51 8ndash19 7






355 13











mice J Nutr 134 1948-1952 24








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1562-1565 12



















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1096 20








Behav 92 39-43 28



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Eng 85 18-28 6









62 15ndash24 15

















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Food Rev Int 26 138-161 13



Nutr Metab 35 134-141 16




498 20












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Environ Res 101 419-428 14







Biochem 18 567-579 21










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997 13



45 1437-1442 16





Pharmacol 84 1259-1265 21











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11ndash18 13

















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UK 13




123 418-422 17





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Kingdom Plantae




Class Magnoliopsida


Family Piperales

Order Piperaceae

Genus Piper L


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1-25 5-9 1 8 6-8 0-5 22-42



04 to 70 20 to 74 15-45 35-12




335 137 34 323



Essential oil


14-704 29-384 07-256 17-190 0-122 03-104 01-410 0-132 0-91 0-97 01-72 NA


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Bioactive compounds


Piperine



Essential oil





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pharmaceuticals





















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et al 2009) 29



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Carr 2010) 3













perspectives 16















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Conclusion 23









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References 5






663 11






Bull 26 1754-1760 17




23 143-150 21




Agents 12 257-262 25







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Food 11 275-281 9













Biophys 464 269-276 22









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50 18ndash23 2



1047-1052 5








66 13










283-289 23








Bao 7 667-70 31

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Med 5 257-262 13



23 1194-1196 16





265-275 21




Pharmacol 43 1401-1407 25




5364 29

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Psych 51 8ndash19 7






355 13











mice J Nutr 134 1948-1952 24








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1562-1565 12



















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1096 20








Behav 92 39-43 28



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Eng 85 18-28 6









62 15ndash24 15

















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Food Rev Int 26 138-161 13



Nutr Metab 35 134-141 16




498 20












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Environ Res 101 419-428 14







Biochem 18 567-579 21










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997 13



45 1437-1442 16





Pharmacol 84 1259-1265 21











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11ndash18 13

















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UK 13




123 418-422 17





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Kingdom Plantae




Class Magnoliopsida


Family Piperales

Order Piperaceae

Genus Piper L


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1-25 5-9 1 8 6-8 0-5 22-42



04 to 70 20 to 74 15-45 35-12




335 137 34 323



Essential oil


14-704 29-384 07-256 17-190 0-122 03-104 01-410 0-132 0-91 0-97 01-72 NA


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Bioactive compounds


Piperine



Essential oil





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et al 2009) 29



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Carr 2010) 3













perspectives 16















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Conclusion 23









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References 5






663 11






Bull 26 1754-1760 17




23 143-150 21




Agents 12 257-262 25







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Food 11 275-281 9













Biophys 464 269-276 22









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50 18ndash23 2



1047-1052 5








66 13










283-289 23








Bao 7 667-70 31

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Med 5 257-262 13



23 1194-1196 16





265-275 21




Pharmacol 43 1401-1407 25




5364 29

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Psych 51 8ndash19 7






355 13











mice J Nutr 134 1948-1952 24








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Behav 92 39-43 28



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Eng 85 18-28 6









62 15ndash24 15

















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Food Rev Int 26 138-161 13



Nutr Metab 35 134-141 16




498 20












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Environ Res 101 419-428 14







Biochem 18 567-579 21










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997 13



45 1437-1442 16





Pharmacol 84 1259-1265 21











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123 418-422 17





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Kingdom Plantae




Class Magnoliopsida


Family Piperales

Order Piperaceae

Genus Piper L


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1-25 5-9 1 8 6-8 0-5 22-42



04 to 70 20 to 74 15-45 35-12




335 137 34 323



Essential oil


14-704 29-384 07-256 17-190 0-122 03-104 01-410 0-132 0-91 0-97 01-72 NA


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Bioactive compounds


Piperine



Essential oil





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Carr 2010) 3













perspectives 16















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Conclusion 23









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References 5






663 11






Bull 26 1754-1760 17




23 143-150 21




Agents 12 257-262 25







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Food 11 275-281 9













Biophys 464 269-276 22









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50 18ndash23 2



1047-1052 5








66 13










283-289 23








Bao 7 667-70 31

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Med 5 257-262 13



23 1194-1196 16





265-275 21




Pharmacol 43 1401-1407 25




5364 29

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Psych 51 8ndash19 7






355 13











mice J Nutr 134 1948-1952 24








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1562-1565 12



















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Behav 92 39-43 28



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Eng 85 18-28 6









62 15ndash24 15

















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Food Rev Int 26 138-161 13



Nutr Metab 35 134-141 16




498 20












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Environ Res 101 419-428 14







Biochem 18 567-579 21










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45 1437-1442 16





Pharmacol 84 1259-1265 21











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123 418-422 17





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Kingdom Plantae




Class Magnoliopsida


Family Piperales

Order Piperaceae

Genus Piper L


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1-25 5-9 1 8 6-8 0-5 22-42



04 to 70 20 to 74 15-45 35-12




335 137 34 323



Essential oil


14-704 29-384 07-256 17-190 0-122 03-104 01-410 0-132 0-91 0-97 01-72 NA


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Piperine



Essential oil





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et al 2009) 29



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Carr 2010) 3













perspectives 16















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Conclusion 23









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References 5






663 11






Bull 26 1754-1760 17




23 143-150 21




Agents 12 257-262 25







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Food 11 275-281 9













Biophys 464 269-276 22









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50 18ndash23 2



1047-1052 5








66 13










283-289 23








Bao 7 667-70 31

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Med 5 257-262 13



23 1194-1196 16





265-275 21




Pharmacol 43 1401-1407 25




5364 29

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Psych 51 8ndash19 7






355 13











mice J Nutr 134 1948-1952 24








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1562-1565 12



















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Behav 92 39-43 28



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Eng 85 18-28 6









62 15ndash24 15

















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Food Rev Int 26 138-161 13



Nutr Metab 35 134-141 16




498 20












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Environ Res 101 419-428 14







Biochem 18 567-579 21










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45 1437-1442 16





Pharmacol 84 1259-1265 21











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UK 13




123 418-422 17





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Kingdom Plantae




Class Magnoliopsida


Family Piperales

Order Piperaceae

Genus Piper L


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1-25 5-9 1 8 6-8 0-5 22-42



04 to 70 20 to 74 15-45 35-12




335 137 34 323



Essential oil


14-704 29-384 07-256 17-190 0-122 03-104 01-410 0-132 0-91 0-97 01-72 NA


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Piperine



Essential oil





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specific purpose


















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et al 2009) 29



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Carr 2010) 3













perspectives 16















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Conclusion 23









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References 5






663 11






Bull 26 1754-1760 17




23 143-150 21




Agents 12 257-262 25







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Food 11 275-281 9













Biophys 464 269-276 22









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50 18ndash23 2



1047-1052 5








66 13










283-289 23








Bao 7 667-70 31

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Med 5 257-262 13



23 1194-1196 16





265-275 21




Pharmacol 43 1401-1407 25




5364 29

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Psych 51 8ndash19 7






355 13











mice J Nutr 134 1948-1952 24








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1096 20








Behav 92 39-43 28



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Eng 85 18-28 6









62 15ndash24 15

















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Food Rev Int 26 138-161 13



Nutr Metab 35 134-141 16




498 20












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Environ Res 101 419-428 14







Biochem 18 567-579 21










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997 13



45 1437-1442 16





Pharmacol 84 1259-1265 21











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123 418-422 17





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Kingdom Plantae




Class Magnoliopsida


Family Piperales

Order Piperaceae

Genus Piper L


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1-25 5-9 1 8 6-8 0-5 22-42



04 to 70 20 to 74 15-45 35-12




335 137 34 323



Essential oil


14-704 29-384 07-256 17-190 0-122 03-104 01-410 0-132 0-91 0-97 01-72 NA


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Piperine



Essential oil





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pharmaceuticals





















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et al 2009) 29



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Carr 2010) 3













perspectives 16















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Conclusion 23









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References 5






663 11






Bull 26 1754-1760 17




23 143-150 21




Agents 12 257-262 25







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Food 11 275-281 9













Biophys 464 269-276 22









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50 18ndash23 2



1047-1052 5








66 13










283-289 23








Bao 7 667-70 31

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Med 5 257-262 13



23 1194-1196 16





265-275 21




Pharmacol 43 1401-1407 25




5364 29

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Psych 51 8ndash19 7






355 13











mice J Nutr 134 1948-1952 24








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1562-1565 12



















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Behav 92 39-43 28



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Eng 85 18-28 6









62 15ndash24 15

















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Food Rev Int 26 138-161 13



Nutr Metab 35 134-141 16




498 20












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Environ Res 101 419-428 14







Biochem 18 567-579 21










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997 13



45 1437-1442 16





Pharmacol 84 1259-1265 21











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123 418-422 17





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Kingdom Plantae




Class Magnoliopsida


Family Piperales

Order Piperaceae

Genus Piper L


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1-25 5-9 1 8 6-8 0-5 22-42



04 to 70 20 to 74 15-45 35-12




335 137 34 323



Essential oil


14-704 29-384 07-256 17-190 0-122 03-104 01-410 0-132 0-91 0-97 01-72 NA


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Piperine



Essential oil





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pharmaceuticals





















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et al 2009) 29



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Carr 2010) 3













perspectives 16















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Conclusion 23









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References 5






663 11






Bull 26 1754-1760 17




23 143-150 21




Agents 12 257-262 25







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Food 11 275-281 9













Biophys 464 269-276 22









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50 18ndash23 2



1047-1052 5








66 13










283-289 23








Bao 7 667-70 31

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Med 5 257-262 13



23 1194-1196 16





265-275 21




Pharmacol 43 1401-1407 25




5364 29

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Psych 51 8ndash19 7






355 13











mice J Nutr 134 1948-1952 24








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1562-1565 12



















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1096 20








Behav 92 39-43 28



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Eng 85 18-28 6









62 15ndash24 15

















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Food Rev Int 26 138-161 13



Nutr Metab 35 134-141 16




498 20












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Environ Res 101 419-428 14







Biochem 18 567-579 21










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997 13



45 1437-1442 16





Pharmacol 84 1259-1265 21











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UK 13




123 418-422 17





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Kingdom Plantae




Class Magnoliopsida


Family Piperales

Order Piperaceae

Genus Piper L


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1-25 5-9 1 8 6-8 0-5 22-42



04 to 70 20 to 74 15-45 35-12




335 137 34 323



Essential oil


14-704 29-384 07-256 17-190 0-122 03-104 01-410 0-132 0-91 0-97 01-72 NA


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Essential oil





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Carr 2010) 3













perspectives 16















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Conclusion 23









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References 5






663 11






Bull 26 1754-1760 17




23 143-150 21




Agents 12 257-262 25







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Food 11 275-281 9













Biophys 464 269-276 22









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50 18ndash23 2



1047-1052 5








66 13










283-289 23








Bao 7 667-70 31

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Med 5 257-262 13



23 1194-1196 16





265-275 21




Pharmacol 43 1401-1407 25




5364 29

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Psych 51 8ndash19 7






355 13











mice J Nutr 134 1948-1952 24








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1562-1565 12



















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1096 20








Behav 92 39-43 28



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Eng 85 18-28 6









62 15ndash24 15

















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Food Rev Int 26 138-161 13



Nutr Metab 35 134-141 16




498 20












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Environ Res 101 419-428 14







Biochem 18 567-579 21










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997 13



45 1437-1442 16





Pharmacol 84 1259-1265 21











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11ndash18 13

















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UK 13




123 418-422 17





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Kingdom Plantae




Class Magnoliopsida


Family Piperales

Order Piperaceae

Genus Piper L


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1-25 5-9 1 8 6-8 0-5 22-42



04 to 70 20 to 74 15-45 35-12




335 137 34 323



Essential oil


14-704 29-384 07-256 17-190 0-122 03-104 01-410 0-132 0-91 0-97 01-72 NA


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Piperine



Essential oil





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pharmaceuticals





















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Carr 2010) 3













perspectives 16















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Conclusion 23









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References 5






663 11






Bull 26 1754-1760 17




23 143-150 21




Agents 12 257-262 25







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Food 11 275-281 9













Biophys 464 269-276 22









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50 18ndash23 2



1047-1052 5








66 13










283-289 23








Bao 7 667-70 31

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Med 5 257-262 13



23 1194-1196 16





265-275 21




Pharmacol 43 1401-1407 25




5364 29

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Psych 51 8ndash19 7






355 13











mice J Nutr 134 1948-1952 24








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1562-1565 12



















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Behav 92 39-43 28



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Eng 85 18-28 6









62 15ndash24 15

















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Food Rev Int 26 138-161 13



Nutr Metab 35 134-141 16




498 20












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Environ Res 101 419-428 14







Biochem 18 567-579 21










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997 13



45 1437-1442 16





Pharmacol 84 1259-1265 21











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11ndash18 13

















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UK 13




123 418-422 17





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Kingdom Plantae




Class Magnoliopsida


Family Piperales

Order Piperaceae

Genus Piper L


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1-25 5-9 1 8 6-8 0-5 22-42



04 to 70 20 to 74 15-45 35-12




335 137 34 323



Essential oil


14-704 29-384 07-256 17-190 0-122 03-104 01-410 0-132 0-91 0-97 01-72 NA


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Bioactive compounds


Piperine



Essential oil





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Carr 2010) 3













perspectives 16















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Conclusion 23









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References 5






663 11






Bull 26 1754-1760 17




23 143-150 21




Agents 12 257-262 25







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Behav 92 39-43 15















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Food 11 275-281 9













Biophys 464 269-276 22









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50 18ndash23 2



1047-1052 5








66 13










283-289 23








Bao 7 667-70 31

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Med 5 257-262 13



23 1194-1196 16





265-275 21




Pharmacol 43 1401-1407 25




5364 29

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Psych 51 8ndash19 7






355 13











mice J Nutr 134 1948-1952 24








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1562-1565 12



















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1096 20








Behav 92 39-43 28



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Eng 85 18-28 6









62 15ndash24 15

















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Food Rev Int 26 138-161 13



Nutr Metab 35 134-141 16




498 20












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Environ Res 101 419-428 14







Biochem 18 567-579 21










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997 13



45 1437-1442 16





Pharmacol 84 1259-1265 21











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11ndash18 13

















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UK 13




123 418-422 17





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Kingdom Plantae




Class Magnoliopsida


Family Piperales

Order Piperaceae

Genus Piper L


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1-25 5-9 1 8 6-8 0-5 22-42



04 to 70 20 to 74 15-45 35-12




335 137 34 323



Essential oil


14-704 29-384 07-256 17-190 0-122 03-104 01-410 0-132 0-91 0-97 01-72 NA


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Bioactive compounds


Piperine



Essential oil





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specific purpose


















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Conclusion 23









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References 5






663 11






Bull 26 1754-1760 17




23 143-150 21




Agents 12 257-262 25







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Behav 92 39-43 15















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Food 11 275-281 9













Biophys 464 269-276 22









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50 18ndash23 2



1047-1052 5








66 13










283-289 23








Bao 7 667-70 31

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Med 5 257-262 13



23 1194-1196 16





265-275 21




Pharmacol 43 1401-1407 25




5364 29

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Psych 51 8ndash19 7






355 13











mice J Nutr 134 1948-1952 24








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1562-1565 12



















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1096 20








Behav 92 39-43 28



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Eng 85 18-28 6









62 15ndash24 15

















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Food Rev Int 26 138-161 13



Nutr Metab 35 134-141 16




498 20












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Environ Res 101 419-428 14







Biochem 18 567-579 21










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997 13



45 1437-1442 16





Pharmacol 84 1259-1265 21











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11ndash18 13

















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UK 13




123 418-422 17





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Kingdom Plantae




Class Magnoliopsida


Family Piperales

Order Piperaceae

Genus Piper L


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1-25 5-9 1 8 6-8 0-5 22-42



04 to 70 20 to 74 15-45 35-12




335 137 34 323



Essential oil


14-704 29-384 07-256 17-190 0-122 03-104 01-410 0-132 0-91 0-97 01-72 NA


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Bioactive compounds


Piperine



Essential oil





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specific purpose


















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pharmaceuticals





















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References 5






663 11






Bull 26 1754-1760 17




23 143-150 21




Agents 12 257-262 25







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Behav 92 39-43 15















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20









Food 11 275-281 9













Biophys 464 269-276 22









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50 18ndash23 2



1047-1052 5








66 13










283-289 23








Bao 7 667-70 31

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Med 5 257-262 13



23 1194-1196 16





265-275 21




Pharmacol 43 1401-1407 25




5364 29

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Psych 51 8ndash19 7






355 13











mice J Nutr 134 1948-1952 24








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1562-1565 12



















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1096 20








Behav 92 39-43 28



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Eng 85 18-28 6









62 15ndash24 15

















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Food Rev Int 26 138-161 13



Nutr Metab 35 134-141 16




498 20












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Environ Res 101 419-428 14







Biochem 18 567-579 21










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45 1437-1442 16





Pharmacol 84 1259-1265 21











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Class Magnoliopsida


Family Piperales

Order Piperaceae

Genus Piper L


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04 to 70 20 to 74 15-45 35-12




335 137 34 323



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14-704 29-384 07-256 17-190 0-122 03-104 01-410 0-132 0-91 0-97 01-72 NA


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Behav 92 39-43 15















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Food 11 275-281 9













Biophys 464 269-276 22









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50 18ndash23 2



1047-1052 5








66 13










283-289 23








Bao 7 667-70 31

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Med 5 257-262 13



23 1194-1196 16





265-275 21




Pharmacol 43 1401-1407 25




5364 29

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Psych 51 8ndash19 7






355 13











mice J Nutr 134 1948-1952 24








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Eng 85 18-28 6









62 15ndash24 15

















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Nutr Metab 35 134-141 16




498 20












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Biochem 18 567-579 21










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45 1437-1442 16





Pharmacol 84 1259-1265 21











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Class Magnoliopsida


Family Piperales

Order Piperaceae

Genus Piper L


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04 to 70 20 to 74 15-45 35-12




335 137 34 323



Essential oil


14-704 29-384 07-256 17-190 0-122 03-104 01-410 0-132 0-91 0-97 01-72 NA


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Food 11 275-281 9













Biophys 464 269-276 22









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50 18ndash23 2



1047-1052 5








66 13










283-289 23








Bao 7 667-70 31

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Med 5 257-262 13



23 1194-1196 16





265-275 21




Pharmacol 43 1401-1407 25




5364 29

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355 13











mice J Nutr 134 1948-1952 24








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Eng 85 18-28 6









62 15ndash24 15

















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Nutr Metab 35 134-141 16




498 20












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Biochem 18 567-579 21










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45 1437-1442 16





Pharmacol 84 1259-1265 21











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Class Magnoliopsida


Family Piperales

Order Piperaceae

Genus Piper L


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04 to 70 20 to 74 15-45 35-12




335 137 34 323



Essential oil


14-704 29-384 07-256 17-190 0-122 03-104 01-410 0-132 0-91 0-97 01-72 NA


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50 18ndash23 2



1047-1052 5








66 13










283-289 23








Bao 7 667-70 31

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23 1194-1196 16





265-275 21




Pharmacol 43 1401-1407 25




5364 29

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Psych 51 8ndash19 7






355 13











mice J Nutr 134 1948-1952 24








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Behav 92 39-43 28



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Eng 85 18-28 6









62 15ndash24 15

















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Food Rev Int 26 138-161 13



Nutr Metab 35 134-141 16




498 20












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Environ Res 101 419-428 14







Biochem 18 567-579 21










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45 1437-1442 16





Pharmacol 84 1259-1265 21











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123 418-422 17





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Class Magnoliopsida


Family Piperales

Order Piperaceae

Genus Piper L


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1-25 5-9 1 8 6-8 0-5 22-42



04 to 70 20 to 74 15-45 35-12




335 137 34 323



Essential oil


14-704 29-384 07-256 17-190 0-122 03-104 01-410 0-132 0-91 0-97 01-72 NA


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Med 5 257-262 13



23 1194-1196 16





265-275 21




Pharmacol 43 1401-1407 25




5364 29

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355 13











mice J Nutr 134 1948-1952 24








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Behav 92 39-43 28



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Eng 85 18-28 6









62 15ndash24 15

















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Nutr Metab 35 134-141 16




498 20












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Environ Res 101 419-428 14







Biochem 18 567-579 21










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45 1437-1442 16





Pharmacol 84 1259-1265 21











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Class Magnoliopsida


Family Piperales

Order Piperaceae

Genus Piper L


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04 to 70 20 to 74 15-45 35-12




335 137 34 323



Essential oil


14-704 29-384 07-256 17-190 0-122 03-104 01-410 0-132 0-91 0-97 01-72 NA


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Psych 51 8ndash19 7






355 13











mice J Nutr 134 1948-1952 24








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Behav 92 39-43 28



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Eng 85 18-28 6









62 15ndash24 15

















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Food Rev Int 26 138-161 13



Nutr Metab 35 134-141 16




498 20












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Environ Res 101 419-428 14







Biochem 18 567-579 21










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45 1437-1442 16





Pharmacol 84 1259-1265 21











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Class Magnoliopsida


Family Piperales

Order Piperaceae

Genus Piper L


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04 to 70 20 to 74 15-45 35-12




335 137 34 323



Essential oil


14-704 29-384 07-256 17-190 0-122 03-104 01-410 0-132 0-91 0-97 01-72 NA


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Eng 85 18-28 6









62 15ndash24 15

















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Food Rev Int 26 138-161 13



Nutr Metab 35 134-141 16




498 20












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Environ Res 101 419-428 14







Biochem 18 567-579 21










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45 1437-1442 16





Pharmacol 84 1259-1265 21











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Class Magnoliopsida


Family Piperales

Order Piperaceae

Genus Piper L


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Behav 92 39-43 28



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Eng 85 18-28 6









62 15ndash24 15

















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Nutr Metab 35 134-141 16




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Biochem 18 567-579 21










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45 1437-1442 16





Pharmacol 84 1259-1265 21











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Class Magnoliopsida


Family Piperales

Order Piperaceae

Genus Piper L


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335 137 34 323



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14-704 29-384 07-256 17-190 0-122 03-104 01-410 0-132 0-91 0-97 01-72 NA


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Eng 85 18-28 6









62 15ndash24 15

















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Food Rev Int 26 138-161 13



Nutr Metab 35 134-141 16




498 20












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Biochem 18 567-579 21










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Family Piperales

Order Piperaceae

Genus Piper L


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14-704 29-384 07-256 17-190 0-122 03-104 01-410 0-132 0-91 0-97 01-72 NA


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Family Piperales

Order Piperaceae

Genus Piper L


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04 to 70 20 to 74 15-45 35-12




335 137 34 323



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14-704 29-384 07-256 17-190 0-122 03-104 01-410 0-132 0-91 0-97 01-72 NA


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Pharmacol 84 1259-1265 21











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123 418-422 17





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Kingdom Plantae




Class Magnoliopsida


Family Piperales

Order Piperaceae

Genus Piper L


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14-704 29-384 07-256 17-190 0-122 03-104 01-410 0-132 0-91 0-97 01-72 NA


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Pharmacol 84 1259-1265 21











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123 418-422 17





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Class Magnoliopsida


Family Piperales

Order Piperaceae

Genus Piper L


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1-25 5-9 1 8 6-8 0-5 22-42



04 to 70 20 to 74 15-45 35-12




335 137 34 323



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14-704 29-384 07-256 17-190 0-122 03-104 01-410 0-132 0-91 0-97 01-72 NA


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Essential oil





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Pharmacol 84 1259-1265 21











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123 418-422 17





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Class Magnoliopsida


Family Piperales

Order Piperaceae

Genus Piper L


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335 137 34 323



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14-704 29-384 07-256 17-190 0-122 03-104 01-410 0-132 0-91 0-97 01-72 NA


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123 418-422 17





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Family Piperales

Order Piperaceae

Genus Piper L


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14-704 29-384 07-256 17-190 0-122 03-104 01-410 0-132 0-91 0-97 01-72 NA


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Family Piperales

Order Piperaceae

Genus Piper L


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BLACK PEPPER AND HEALTH CLAIMS: A COMPREHENSIVE TREATISE

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