Slide 1

Role of Plant Flavonoids In Mammalian Cell Inflammation

Dahiphale Hanumant Venkatrao

DEPARTMENT OF VETERINARY PHARMACOLOGY AND TOXICOLOGY

COVAS, PARBHANI

1

Introduction

Flavonoids(orbioflavonoids)

Derived from the Latin wordflavusmeaning yellow color in nature

class ofplantsecondary metabolites.

Also referred to as Vitamin P.

Flavonoids: source

Fruit and vegetables:

(All classes)

Red wine:

(Flavanol, Flavonols)

Cocoa:

(Flavanols )

Tea:

(Flavanols)

Berries:

(Anthocyanins)

Citrus:

(Flavanone)

Dietary sources

3

Seperation techniques

Thin layer chromatography (TLC)

High Performance Liquid Chromatography

Paper Chromatography

Column Chromatography

structures

These are low molecular weight substances.

Are phenylbenzo- pyrones.

Structures are based on a common three-ring nucleus.

Flavonoids: structure

Flavanol

Flavonol

Isoflavone

Flavanone

Anthocyanin

R2

HO

O

R1

R3

OH

OH

O

O

R1

R2

R4

R3

R5

O

+

OH

HO

OH

OH

R1

R2

O

O

HO

OH

OH

R1

R2

R3

O

HO

OH

O

R1

R2

R3

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1) Antioxidative activities

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

Anti-inflammatory mechanisms of flavonoids

Antioxidative activities

Antioxidative activities

Inhibition of ROS production

Free radical

Lipid peroxidation

Inhibition of pro-oxidant enzyme

Radical scavanging

EFFECT

MECHANISM

ACTIVITY

Body cells and tissues are continuously in danger by the damage caused by free radicals and reactive oxygen species.

which are produced during normal oxygen metabolism.

The increased production of reactive oxygen species leads to forms of tissue injury. which have been implicated in a multitude of disease states ranging from inflammatory injury to myocardial infarction and cancer.

The mechanisms and the sequence of events by which free radicals interfere with cellular functions are not fully understood

But some of the detrimental effects in biological systems includes.

Peroxidation of membrane lipids,

Oxidative damage to nucleic acids or carbohydrates and

The oxidation of sulfhydryl and other susceptible groups in proteins.

In addition, free radicals can attract various inflammatory mediators contributing to a generalized inflammatory response and tissue damage

flavonoids are powerful in vitro antioxidants, being able to scavenge a wide range of free radicals, as well as to inhibit their formation.

Modulation of inflammatory related cell functions

Modulation of

inflammatory

cell

Modulation of enzymatic activity

Inflammatory cells activation

Modulation of

Secretory procesess

ACTIVITY

MECHANISM

EFFECT

The immune system is integrated by a highly complex regulated group of cells. that may interact in a cellcell manner and may also respond to intercellular messages.

The immune response can be modified by

Diet

pharmacological agents

environmental pollutants

and naturally occurring food chemicals such as vitamins and flavonoids.

Some flavonoids show a remarkable biochemical and pharmacological actions, that affect the function of immune and inflammatory cells such as

T cells,

B cells,

macrophages,

neutrophils,

mast cells, or basophils.

Several flavonoids specifically affect enzyme systems critically involved in the generation of inflammatory processes.

especially tyrosine and serine-threonine protein kinases.

These enzymes are involved in signaling transduction and cell activation processes such as

T cell proliferation,

B lymphocyte activation or

cytokine production by stimulated monocytes

Modulation of proinflammatory enzyme activities

Modulation of

proinflammatory

enzymes

inhibition of Arachidonic acid enzyme

Inflammatory mediators:

NO, Leukotrienes, prostaglandins

inhibition of NO synthase

EFFECT

MECHANISM

ACTIVITY

Many investigations have shown that different flavonoid molecules modulate the activity of arachidonic acid metabolizing enzymes such as

phospholipase ,

cyclooxygenase (COX) and lipoxygenase (LOX)

And the nitric oxide (NO) producing enzyme, nitric oxide synthase (NOS).

The inhibition of these enzymes reduces the production of AA, prostaglandins, leucotrienes, and NO. which are mediators of inflammation.

Thus, the inhibition of these enzymes by flavonoids may be one of the most important mechanisms of their anti-inflammatory activity.

Modulation of the production of other proinflammatory molecules

Modulation of proinflammatory mediators

Modulation of cytokine production

Inflammatory

Cytokine:

TNF- ,

Interleukines.

EFFECT

MECHANISM

ACTIVITY

In addition to COX-2 several cytokines are deeply associated with inflammatory diseases

In particular, tumor necrosis factor-a (TNF-a) is prominent contributors to chronic inflammatory responses.

flavonoids are required for optimal inhibition of LPS stimulated TNF-a release.

Modulation of proinflammatory gene expression

Modulation of proinflammatory gene expression

Modulation of signal transduction

proinflammatory

Gene transcription

EFFECT

MECHANISM

ACTIVITY

Several lines of evidence shows that certain flavonoids are modulators of proinflammatory gene expression by attenuation of the inflammatory response

It is not known to what extent these proinflammatory gene expression changes contribute to the inflammatory response

but is evident that flavonoids show anti-inflammatory activity, at least in part, by affecting mRNA levels.

CONCLUSIONS

Excessive inflammation is considered as a critical factor in many human diseases, including two of the most extended burdens in the world: cancer and cardiovascular diseases.

Epidemiological studies have demonstrated an inverse relationship between dietary flavonoid intake and prevalence and risk of these diseases.

Thus flavonoids play a vital role in reducing cancer and cardiovascular diseases.

References

Flavonoids as anti-inflammatory agents: implications in cancer and cardiovascular disease

Ana 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, and Cancer

ELLIOTT MIDDLETON, JR., CHITHAN KANDASWAMI AND THEOHARIS C. THEOHARIDES1

References

Organic Chemistry of Natural products Vol 2- Gurdeep.R.Chatwal

Organic Chemistry- Reactions and Reagents-O.P Aggarwal

Chemistry of Natural Products- SV Bhat, BH Nagasampagi, M.Sivakumar

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