A REVIEW ON PHYTOCHEMICAL, PHARMACOLOGICAL AND … · Nelli, Telugu: Usirikaya, Kashmir: Aonla. Botanical description A small to medium sized deciduous tree, 8-18 meters height with

www.wjpr.net Vol 6, Issue 7, 2017.

817

Ajay et al. World Journal of Pharmaceutical Research

A REVIEW ON PHYTOCHEMICAL, PHARMACOLOGICAL AND

POTENTIAL THERAPEUTIC USES OF PHYLLANTHUS EMBLICA

Ajay Mandal1* and Jagan Mohan Reddy

2

1,2

Department of Biotechnology Engineering, Acharya Institute of Technology, Bangalore-

560107, INDIA.

ABSTRACT

Amla has a hallowed position in Ayurveda- an Indian indigenous

system of medicine. According to belief in Indian mythology, Amla is

the first tree to be created in the universe; which belongs to the family

of Euphorbiaceae and is also known as Phyllanthus emblica or Indian

gooseberry. Amla is native to India and also grows in tropical and

subtropical regions of Pakistan, Uzbekistan, Sri Lanka, South East

Asia, China and Malaysia.[1]

The fruits of Amla are widely used in the

Ayurvedic preparation and are believed to increase defence against

diseases. It has a beneficial role in degenerative diseases like cancer,

diabetes, liver treatment, ulcer, anaemia, heart trouble1 and also is an

important constituent in hepatoprotective formulas available.[2]

KEYWORDS: Medicinal plant, Phyllanthus emblica, pharmacology, phytochemistry.

INTRODUCTION

SCIENTIFIC CLASSIFICATION

Synonym: Phyllanthus emblica Linn

Kingdom: Plantae

Division: Angiospermae

Class: Dicotyledonae

Order: Geraniales

Family: Euphorbiaceae

Genus: Emblica

Species: officinalis Geartn.

World Journal of Pharmaceutical Research SJIF Impact Factor 7.523

Volume 6, Issue 7, 817-830. Review Article ISSN 2277– 7105

*Corresponding Author

Ajay Mandal

Department of

Biotechnology Engineering,

Acharya Institute of

Technology, Bangalore-

560107, INDIA.

Article Received on

15 May 2017,

Revised on 05 June 2017,

Accepted on 25 June 2017

DOI: 10.20959/wjpr20177-8869


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VERNACULAR NAMES

English: Emblic myrobalan, Indian Goose berry, Sanskrit: Aamalaki, Hindi: Amla,

Kannada: Nelli Kayi, Marathi: Amla, Gujarati: Ambla, Malayalam: Nelli Kayi, Tamil:

Nelli, Telugu: Usirikaya, Kashmir: Aonla.

Botanical description

A small to medium sized deciduous tree, 8-18 meters height with thin light grey bark

exfoliating in small thin irregular flakes, leaves are simple, subsessile, closely set along the

branchlets, light green having the appearance of pinnate leaves; flowers are greenish yellow,

in axillary fascicles, unisexual, males numerous on short slender pedicels, females few,

subsessile, ovary 3-celled; fruits globose, fleshy, pale yellow with six obscure vertical

furrows enclosing six trigonous seeds in 2-seeded 3 crustaceous cocci.[3]

Geographical distribution

Amla is found throughout India, the sea-coast districts and on hill slopes up to 200 meters,

and is also cultivated in plains.[4]

It is a potential crop which grows in the marginal soils and

various kinds degraded lands such as salt-affected soils, saline’s and dry and semi-dry

regions. It is common all over tropical and sub-tropical India and also found in Burma[5]

, it is

abundant in deciduous forests of Madhya Pradesh also grows in tropical and subtropical parts

of Ceylon, Malay Peninsula and China.[6]

PHYTOCHEMISTRY OF PHYLLANTHUS EMBLICA

Amla Fruit: The average composition of Amla fruits are: moisture 81.2%, protein 0.5%, fat

0.1%, carbohydrates 14.1%, mineral matter 0.7%, fiber 3.4%, Ca 0.05%, K 0.02%, Fe 1.2

mg/100g, nicotinic acid 0.2 mg/g, phyllemblin, phyllemblic acid, gallic acid, emblicol,


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quercetin, hydroxymethyl furfural, ellagic acid, pectin[7-8]

, putranjivan A,[9]

two new

hydrolysable tannins called emblicannin A and B, punigluconin and pendunculagin.[10]

Seeds

A fixed oil, phosphatides and a small quantity of essential oil are present in seed. The fixed

oil yield (16%) has the following physical and chemical properties: acid value 12.7,

saponification value 185, acetyl value 2.03, iodine value 139.5, unsaponifiable matter 3.81%,

sterol 2.70%, saturated fatty acids 7%, linolenic acid (8.78%), linoleic acid (44.0%), oleic

acid (28.40%), stearic acid (2.15 %), palmitic acid (2.99%) and myristic acid (0.95%)5. Arora

et al. (2011)14 also reported that the seed oil is rich in unsaturated fatty acids like linoleic

acid (18:2n-6) and oleic acid.[11]

Leaves & Bark

Gallic acid, ellagic acid, chebulic acid, chebulagic acid, chebulinic acid, a gallotannins called

amlic acid, alkaloids, phyllatidine and phyllantine are reported to be present in Amla tree

leaves.[13-14]

Leucodephinidin, tannin and proanthoyanidin have been reported in the bark of

Amla tree.[13]

Table: 1 The classes of chemical constituents reported in Amla plant[12]

Class Compound

Alkaloid Phyllantine, phyllantidine, zeatin, zeatin nucleotide, zeatin rioside

Benzoid

chebulic acid, chebulinic acid, chebulagic acid, gallic acid ellagic acid, amlaic acid,

3-6-di-O-galloyl-glucose, ethyl gallate b-glucogallin, 1,6,di-O-galloyl-b-D-glucose,

putranjivan A, digallic acid, phyllemblic acid, emlicol music (= galacteric acid)

Diterpene gibberellin A-1, gibberellin A-3, gibberellin A-4, giberellin A-9

Triterpene lupeo

Flavonoid Leucodelphinidin, kaempherol, kaempherol-3-glucoside, rutin Quercetin,

kaempherol-3-O- β -D-glucoside, quercetin -3-O- β -D glucoside

Furanolactone Ascorbic acid

Sterol β-sitosterol

Carbohydrate glucose


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TRADITIONAL USES

The fruits are sour, astringent, bitter, acrid, sweet, cooling, anodyne, ophthalmic, carminative,

digestive, stomachic, laxative, alterant, aphrodisiac, rejuvenative, diuretic, antipyretic and

tonic. They are useful in vitiated conditions of tridosha, diabetes, cough, asthma, bronchitis,

cephalalgia, ophthalmopathy, dyspepsia, colic, flatulence, hyperacidity, peptic ulcer,

erysipelas, skin diseases, leprosy, haematogenesis, inflammations, anemia, emaciation,

hepatopathy, jaundice, strangury, diarrhoea, dysentery, hemorrhages, leucorrhoea,

menorrhagia, cardiac disorders, intermittent fevers and greyness of hair.[15-20]


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PHARMACOLOGICAL ACTIVITIES OF PHYLLANTHUS EMBLICA

Antitumor Activity

Aqueous extract of emblica officinalis was found to be cytotoxic to L 929 cells in culture in a

dose Dependent manner. Concentration needed for 50% inhibition was found to be 16.5g/ml.

Emblica officinalis and chyawanprash (a non-toxic herbal preparation containing 50% E.

extracts were found to reduce ascites and solid tumoues in mice induced by DLA cells.

Animals treated with 1.25 g/kg b.wt. of emblica officinalis extract increased life span of

tumour bearing animals (20%) while animals treated with 2.5 g/kg b.wt of Chyavanaprash

produced 60.9% increased in the life span. Both emblica officinalis and chyavanaprash

significantly reduced the solid tumours. Tumour volume of control animals on 30th day was

4.6 ml whereas animals treated with 1.25 g/kg b.wt of emblica officinalis extract and 2.5 g/kg

b.wt chyavanaprash showed tumour volume of 1.75 and 0.75 ml, respectively emblica

officinalis extract was found to inhibit cell cycle regulating enzymes cdc 25 phosphates in a

dose dependent manner. Concentration needed or 50% inhibition of cdc 25 phosphatase was

found to be 5 g/ml and that needed for inhibition of cdc2 Chinese was found to be>100g/ml.

The results suggest that antitumor activity of emblica officinalis extract may partially be due

to its interaction with cell cycle regulation.[21-24]

Hepatoprotective Activity

Hepatoprotective activity of emblica officinalis (EO) and chyavanaprash (CHY) extracts was

studied using Carbon tetrachloride induced liver injury model in rats. EO and CHY extracts

were found to inhibit the hepatotoxicity produced by acute and chronic administration as seen

from the decreased levels of serum and liver lipid peroxides (LPO), glutamate-pyruvate

transaminase (GPT) and alkaline phosphatase (ALP). Chronic CCI (4) administration was

also found to produce liver fibrosis as seen from the increased levels of collagen hydroxyl

proline and pathological analysis. EO and CHY extracts were found to reduce the elevated

levels significantly, indicating that the extract could inhibit the induction of fibrosis in rats.[21-

24]

Antioxidant Activity

Pre-treatment with the butanol extract of the water fraction of Phyllanthus emblica fruits at

the dose of 100 mg/kg body-weight, orally administered to rats for 10 consecutive days, was

found to enhance secretion of gastric mucus and hexosamine (P<0.001) in the Indomethacin

induced ulceration of rats. The morphological observations also supported a protective effect


822


of the stomach wall from lesion. The Indomethacin treatment of the premedicated animals

with the drug hardly affected either the malondialdehyde (MDA) or superoxide dismutase

(SOD) level in gastric tissue while the ulcerative agent itself significantly enhanced both the

evels. An antioxidant property appears to be predominantly responsible for this cyto

protective action of the drug. The antioxidant activity of tannoid active principles of E.

officinalis consisting of emblicanin A (37%) emblicanin B (33%), punigluconin (12%) and

pedunculagin (14%), was investigated on the basis of their effects on rat brain frontal cortical

and striatal concentrations of the oxidative free radical scavenging enzymes, superoxide

dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) and lipid peroxidation,

in terms of thiobarbituric acidreative products. The results were compared with effects

induced by depresnl, a selective monoamine oxidase (MAO) B inhibitor with well

documented antioxidant activity. The active tannoids of E. officinalis (EOT), Administered in

the doses of 5 and 10 mg/kg, i.p and deprenyl (2 mg/kg, i.p), induced an increase in both

frontal cortical and striatal SOD, CAT and GPX activity, with concomitant decrease in lipid

per oxidation in these areas when administered once daily for 7 days. Acute single

administration of EOT and deprecyl had insignificant effects. The results also indicate that

the antioxidant activity of E. officinalis may reside in the tannoids of the fruits of the plant,

which have vitamin Clike properties rather than vitamin C itself.[21-24]

Cancer

Triphala has been reported to exibit chemopreventive potential. The presence of Triphala in

diet had significantly lowered the benzo(a)pyrene [B(a)P] induced forestomach

papillomagenesis in mice. It was more effective in reducing tumor incidences compared to its

individual constituents. Triphala also significantly increased the antioxidant status of animals

which might have contributed to the chemoprevention.[25]

The breast cancer is one of the

most common cancers in women. Lipid-metabolizing enzymes, lipids and lipoproteins have

been associated with the risk of breast cancer. Kalpaamruthaa (KA) is a modified Siddha

preparation containing EO, Semecarpus anacardium (SA and honey. The elevated levels of

free cholesterol, total cholesterol, triglycerides, phospholipids and free fatty acids and

decreased levels of ester cholesterol in plasma, kidney and liver found in cancer suffering

animals were reverted back to near normal levels on treatment with KA and SA.[26]

Chemoprevention with food phytochemicals is presently considered as one of the most

important strategies to control cancer. EO is valued for its unique tannins and flavanoids,

which exhibit very powerful antioxidant properties. The inhibition of tumor incidences by


823


fruit extract of this plant has been evaluated on two-stage process of skin carcinogenesis in

Swiss albino mice. Chemopreventive potential of EO fruit extract on 7,12-

dimethylbenz(a)anthracene (DMBA) induced skin tumorigenesis in Swiss albino mice have

been found.[27]

The cytotoxic effects of aqueous extract of Triphala were investigated on a

transplantable mouse thymic lymphoma (barcl-95) and human breast cancer cell line (MCF-

7). The differential response of normal cells and tumor cells to Triphala invitro and the

substantial regression of transplanted tumor in mice fed with Triphala indicate to its potential

use as an anticancer drug for clinical treatment.[28]

The suppression of the growth of cancer

cells due to the gallic acid-a major polyphenol as observed in "Triphala" have been

reported.[29]

Ethanolic extract of EO was experimentally evaluated for protection against

genotoxicity induced by DMBA. EO fruit administered orally at different concentrations

(100, 250, 500 mg/kg b.wt) for seven consecutive days in Swiss albino mice prior to a single

intraperitoneal injection of DMBA decreased the frequency of bone marrow micronuclei. The

protection provided by EO may be due to its antioxidant capacity and through its modulatory

effect on hepatic activation and detoxifying enzymes.[30]

Phenolic compounds derived from

plant exhibit a number of beneficial effects and can potentially inhibit several stages of

carcinogenesis. Efficacy of EO polyphenol fraction (EOP) on the induction of apoptosis in

mouse and human carcinoma cell lineses and its modulatory effect on N- nitrosodiethylamine

(NDEA) induced liver tumors in rats was also investigated. EOP treatment could induce

apoptosis in Dalton's Lymphoma Ascites (DLA) and CeHa cell lines. EOP also inhibited

DNA topoisomerase I in Saccharomyces cervisiae, mutant cell cultures and the activity of

cdc25 tyrosine phosphatase.[31]

Invitro antiproliferative activity of extracts from medicinal

plants toward human tumor cell lines, including human erythromyeloid K562, T-lymphoid

Jurkat, B-lymphoid Raji, erythroleukemic HEL cell lines were compared. Extracts from EO

were the most active in inhibiting invitro cell proliferation have been found.[32]

Cyclophosphamide is one of the most famous alkylating anticancer drugs in spite of its toxic

side effects including hematotoxicity, immunotoxicity and mutagenicity. EO or its medicinal

preparations may prove to be beneficial as a component of combination therapy in cancer

patients under cyclophosphamide treatment.[33]

Phenolic compounds and the major

components from the fruit juice of EO and from the branches, leaves and roots showed

stronger inhibition against B16F10 cell growth than against HeLa and MK-1 cell growth.

Norsesquiterpenoid glycosides from the roots showed significant antiproliferative

activities.[34]


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Diabetes

Oral administration of the extracts (100 mg/kg body weight) reduced the blood sugar level in

normal and in alloxan (120 mg/kg) diabetic rats significantly within 4 hours. EO and an

enriched fraction of its tannoids are effective in delaying development of diabetic cataract in

rats.[35]

Aldose reductase (AR) has its involvement in the development of secondary

complications of diabetes including cataract. EO is proved as an important inhibitor of AR.

Exploring the therapeutic value of natural ingredients that people can incorporate into

everyday life may be an effective approach in the management of diabetic complications.[36]

Cardioprotective Activity

The effects of chronic oral administration of fresh fruit homogenate of Amla on myocardial

antioxidant system and oxidative stress induced by ischemic-reperfusion injury (IRI) were

investigated on heart in rats. Chronic EO administration produces myocardial adaptation by

augmenting endogenous antioxidants and protects rat hearts from oxidative stress associated

with IRI.[37]

Anti-ulcer Activities

A herbo mineral formulation of the Ayurveda medicine named Pepticare, composed of EO,

Glycyrrhiza glabra and Tinospora cordifolia was tested for its anti-ulcer and anti-oxidant

activity in rats. Reports were made that Pepticare exhibit anti-ulcer activity, which can be

attributed to its anti-oxidant property.[38]

Methanolic extract of EO (EOE) was studied against

ulcer. EOE had significant ulcer protective and healing effects and this might be due to its

effects both on offensive and defensive mucosal factors.[39]

Immunomodulation

Immunomodulatory effect of aqueous extracts of Amla was examined by Suja et al. (2009)

on Swiss Albino mice. Administration of extracted Amla powder increased the

haemagglutination antibody titre, sheep red blood cells (sRBCs) in dose dependent manner

and also induced the delayed type of hypersensitivity reaction, macrophage migration index,

and respiratory burst activity of the peritoneal macrophages, total leukocyte count, percentage

lymphocyte distribution, serum globulin and relative lymphoid organ weight.[40]

Oxidative stress

Ischemia-reperfusion (IRI)-induced oxidative stress reduced the activities of cardiac

superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and increased


825


lipid peroxidation in rat65. Administration of Amla juice (50 -100 mg/kg body wt.) or

vitamin E (200 mg/kg body wt) reduced the IRI-induced effects.[41]

Amla fruit was also found

to be effective against mercury induced oxidative stress in rat erythrocytes66. Mercury

chloride oxidative stress decreased the glutathione (GSH), SOD and catalase activity, while

increasing the lipid peroxidation (LPO). Amla extract 100 mg/kg was found to be effective in

ameliorating oxidative stress significantly, while 50 mg/kg of Amla fruit extract could only

reverse the values of LPO and catalase.[42]

In alcohol induced damage

Chronic alcohol consumption may lead to tissue and organ damage, coronary heart diseases,

alcohol liver disease and several other diseases.[43-44]

Reddy et al. (2007) administered 33%

(v/v) alcohol (10 g/kg body weight) and aqueous extract of Amla powder (250 mg/kg body

weight/day) once a day for 60 days. Aqueous Amla extract supplementation increased the

GSH content and also the increased the activities of SOD, CAT and GPx.[45]

Lipid damage

Membrane phospholipases, alteration of the membrane lipid packing and penetration of water

molecule may induce formation by products of lipid oxidation.[46-47]

The induced alterations

in permeability of membranes, transport systems, and loss of membrane-bound enzymes can

eventually lead to cell lysis and death under certain conditions.[48]

The assessment of the

efficiency of Amla to prevent lipid peroxidation was measured by thiobarbituric acid-reactive

substrates, lipid hydroperoxide, conjugated diene and 4-hydroxynonenal.[49]

Amla extracts

have capability to afford excellent protection against iron-mediated lipid peroxidation that

might also be useful in reducing photo-induced iron toxicity. The efficiency of Amla extracts

to protect against lipid damage was correlated with phenolics.[49]

Anila and Vijaya Lakshmi

in 2003 reported that administration of Amla significantly reduced the lipid peroxide content

in cholesterol fed rat.[50]

Memory enhancing ability

Amla powder showed a dose-dependent improvement in memory scores of young and aged

mice75. Supplementation of Amla reversed the amnesia induced by scopolamine (0.4 mg/kg,

i.p.) and diazepam (1 mg/kg, i.p.); brain cholinesterase activity and total cholesterol levels

were also reduced on administration of Amla powder for 15 days75. Their studies revealed

that the Amla may be a useful remedy for the management of Alzheimer's disease on account


826


of its multifarious beneficial effects such as memory improving property, cholesterol

lowering property and anticholinesterase activity.[51]

CULTURAL AND RELIGIOUS SIGNIFICANCE

Amla has been regarded as the sacred tree in India. The tree was worshipped as Mother earth

and is believed to nurture Human kind because the fruits are very nourishing. The leaves,

fruits and Houses are used in worship in India. Kartik Mahatma and Vrat Kaumudi order the

worship of this tree. The leaves are offered to the lord of shri Satyanarayana Vrata, Samba on

Shri Shani Pradosha Vrata and Shiva and Gowri on Nitya Somvara Vrata. In Himachal

Pradesh, this tree is worshipped in the month Kartik as propitious and chaste.[52]

CONCLUSION

The significance of Phyllanthus emblica and its extracts as source of medicines dates back to

centuries and hence it is mentioned in age old art of medicine the “Ayurveda”. It is

remarkably evident that its juice effectively reduces many diseases including the digestive

disorders, respiratory disorders, kidney related problems, cardiovascular disorders, Cancer.

Proper conservation and sustainable use of such plant resources may enhance the longevity of

human life as well as contribute considerably against the drug resistant microorganisms. In

the developing countries, increased cost of medication and their side effects are of great

concern to general public hence opening new channels of pharmacological investigations

focusing on natural medication and diverting human trends toward natural cure. It is strongly

believed that detailed information as presented in this review on the phytochemical and

various biological functions of the extracts might provide detailed evidence for the use of this

plant in different medicines.

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A REVIEW ON PHYTOCHEMICAL, PHARMACOLOGICAL AND … · Nelli, Telugu: Usirikaya, Kashmir: Aonla. Botanical description A small to medium sized deciduous tree, 8-18 meters height with

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