Role of Plant Flavonoids In Mammalian Cell Inflammation Dahiphale Hanumant Venkatrao DEPARTMENT OF VETERINARY PHARMACOLOGY AND TOXICOLOGY COVAS, PARBHANI
Sep 28, 2015
Role of Plant Flavonoids In Mammalian Cell Inflammation
Dahiphale Hanumant Venkatrao
DEPARTMENT OF VETERINARY PHARMACOLOGY AND TOXICOLOGYCOVAS, PARBHANI
Flavonoids (or bioflavonoids) 1) Derived from the Latin word flavus meaning
yellow color in nature2) class of plant secondary metabolites.3) Also referred to as Vitamin P .
Flavonoids: source
Fruit and vegetables:(All classes)
Red wine:(Flavanol, Flavonols)
Cocoa:(Flavanolsand procyanidins)
Tea:(Flavanols)
Berries:(Anthocyanins)
Citrus:(Flavanone)
Dietary sources
Seperation techniques
1) Thin layer chromatography (TLC)2) High Performance Liquid Chromatography3) Paper Chromatography4) Column Chromatography
structures1) These are low molecular weight substances.
2) Are phenylbenzo- pyrones.
3) Structures are based on a common three-
ring nucleus.
Flavonoids: structure
Flavanol
Flavonol
Isoflavone
Flavanone
Anthocyanin
R2
HO O
R1
R3
OHOH
O
O
R1
R2 R4
R3
R5O +
OH
HO
OH
OHR1
R2
O
O
HO
OHOH
R1R2
R3OHO
OH O
R1
R2
R3
1) Antioxidativeactivities
2) Modulation of inflammatory related
cell functions
5) Modulation of proinflammatory gene expression
4) Modulation of the production of other
proinflammatory molecules
3) Modulation of proinflammatory enzyme activities
Proposed mechanisms underlying the inflammatory effects of flavonoids
Several mechanisms explaining the anti-inflammatoryactivity of flavonoids have been described, including
Antioxidative activities
Antioxidativeactivities
Inhibition of ROS
production
Free radical
Lipid peroxidation
Inhibition of pro-oxidant
enzyme
Radical scavanging
EFFECTMECHANISMACTIVITY
1) Body cells and tissues are continuously threatened by thedamage caused by free radicals and reactive oxygenspecies.
2) which are produced during normal oxygen metabolism.
3) The increased production of reactive oxygen species leadsto forms of tissue injury.
4) which have been implicated in a multitude of diseasestates ranging from inflammatory injury to myocardialinfarction and cancer.
5) The mechanisms and the sequence of events by which freeradicals interfere with cellular functions are not fullyunderstood
6) But some of the detrimental effects in biological systemsincludes.
a) Peroxidation of membrane lipids,b) Oxidative damage to nucleic acids or
carbohydrates andc) The oxidation of sulfhydryl and other susceptible
groups in proteins.7) In addition, free radicals can attract various inflammatory
mediators contributing to a generalized inflammatoryresponse and tissue damage
flavonoids are powerful in vitro antioxidants, beingable to scavenge a wide range of free radicals, as well as toinhibit their formation.
Modulation of inflammatory related cell functions
Modulation of inflammatory
related cell functions
Modulation of enzymatic
activity Inflammatory
cells activationModulation of
Secretory procesess
ACTIVITY MECHANISM EFFECT
1) The immune system is integrated by a highly complexregulated group of cells.
2) that may interact in a cellcell manner and may alsorespond to intercellular messages.
3) The immune response can be modified bya) Dietb) pharmacological agentsc) environmental pollutantsd) and naturally occurring food chemicals such as
vitamins and flavonoids.
4) Some flavonoids display a remarkable array ofbiochemical and pharmacological actions.
5) that affect the function of immune and inflammatory cellssuch as
a) T cells,b) B cells,c) macrophages,d) neutrophils,e) mast cells, or basophils.
6) Several flavonoids specifically affect enzyme systemscritically involved in the generation of inflammatoryprocesses.
7) especially tyrosine and serine-threonine protein kinases.8) These enzymes are involved in signaling transduction and
cell activation processes such asa) T cell proliferation,b) B lymphocyte activation orc) cytokine production by stimulated monocytes
Modulation of proinflammatory enzyme activities
Modulation of proinflammatory enzyme activities
inhibition of Arachidonicacid enzyme Inflammatory
mediators:NO, Leukotrienes,
prostaglandinsinhibition of NO synthase
EFFECTMECHANISMACTIVITY
1) Many investigations have shown that different flavonoidmolecules modulate the activity of arachidonic acidmetabolizing enzymes such as
a) phospholipase ,b) cyclooxygenase (COX) and lipoxygenase (LOX)c) And the nitric oxide (NO) producing enzyme,
nitric oxide synthase (NOS).2) The inhibition of these enzymes reduces the production of
AA, prostaglandins, leucotrienes, and NO. which aremediators of inflammation.
3) Thus, the inhibition of these enzymes by flavonoids may beone of the most important mechanisms of their anti-inflammatory activity.
Modulation of the production of other proinflammatory molecules
Modulation of the production of other
proinflammatory molecules
Modulation of cytokine production
InflammatoryCytokine:
TNF- ,Interleukines.
EFFECTMECHANISMACTIVITY
1) In addition to COX-2 several cytokines are deeplyassociated with inflammatory diseases
2) In particular, tumor necrosis factor-a (TNF-a) is prominentcontributors to chronic inflammatory responses.
3) The comparison of molecular structures from differentflavonoids shows that
a) That the presence of a double bond at position C2C3 of the C ring
b) With oxo function at position 4,c) Along with the presence of OH groups at positions
30 and 40 of the B ringare required for optimal inhibition of LPS
stimulated TNF-a release.
Modulation of proinflammatory gene expression
Modulation of proinflammatory gene expression
Modulation of single
transduction
proinflammatoryGene transcription
EFFECTMECHANISMACTIVITY
1) In recent years, several lines of evidence have supportedthe idea that certain flavonoids are modulators ofproinflammatory gene expression
2) thus leading to the attenuation of the inflammatoryresponse
3) It is not known to what extent these proinflammatory geneexpression changes contribute to the inflammatoryresponse
4) but is evident that flavonoids show anti-inflammatoryactivity, at least in part, by affecting mRNA levels.
5) The mechanisms by which flavonoids blockproinflammatory gene expression arecurrently being investigated6) but pioneer studies suggest an effect ontranscriptional activity suppression inresponse to inflammatory stimuli.
CONCLUSIONS
Excessive inflammation is considered as a criticalfactor in many human diseases, including twoof the most extended burdens in the world:cancer and cardiovascular diseases.Epidemiological studies have demonstrated aninverse relationship between dietary flavonoidintake and prevalence and risk of thesediseases.So that, flavonoids research have received muchattention over the past years.
References
Flavonoids as anti-inflammatory agents:implications in cancer and cardiovascular diseaseAna Garca-Lafuente ,Eva Guillamon.Ana Villares,Mauricio A. Rostagno.Jose Alfredo Martnez. The Effects of Plant Flavonoids on Mammalian Cells:Implications for Inflammation, Heart Disease, andCancerELLIOTT MIDDLETON, JR., CHITHAN KANDASWAMIAND THEOHARIS C. THEOHARIDES1
References
Organic Chemistry of Natural products Vol2- Gurdeep.R.Chatwal Organic Chemistry- Reactions and Reagents-O.P Aggarwal Chemistry of Natural Products- SV Bhat, BH Nagasampagi, M.Sivakumar