Role of Plant Flavonoids In

Mammalian Cell Inflammation

Dahiphale Hanumant Venkatrao
DEPARTMENT OF VETERINARY PHARMACOLOGY AND
TOXICOLOGY
COVAS, PARBHANI

Introduction
Flavonoids(orbioflavonoids)
1) Derived
from
the
Latin
wordflavusmeaning yellow color in
nature
2) class ofplantsecondary metabolites.
3) Also referred to as Vitamin P.

Flavonoids:
source
Dietary
sources
Fruit and vegetables:
(All classes)
Tea:
(Flavanols)

Citrus:
(Flavanone)
Red wine:
(Flavanol, Flavonols)

Cocoa:
(Flavanols )
Berries:
(Anthocyanins)

Seperation techniques

1) Thin layer chromatography (TLC)

2) High
Performance
Liquid
Chromatography
3) Paper Chromatography
4) Column Chromatography

structures

1) These

are

low

molecular

weight

substances.
2) Are phenylbenzo- pyrones.
3) Structures are based on a common
three-ring nucleus.

Flavonoids: structure
R1
R1

R2
HO

R3

R3

R1

OH
OH

OH
HO

Flavanol

O+

R2

R4
R5

Isoflavone

R2
OH

OH
R1

Anthocyanin

R1
R2

R2
HO

R3

HO

OH
OH

O
Flavonol

OH

O
Flavanone

R3

Anti-inflammatory mechanisms of
flavonoids

1)
Antioxidative
activities
2) Modulation of
inflammatory related
cell functions

3) Modulation of
proinflammatory
enzyme activities

4) Modulation of the
production of other
proinflammatory
molecules

5) Modulation of
proinflammatory
gene expression

Antioxidative activities
ACTIVITY

MECHANIS
M

Antioxidati
ve
activities

Radical
scavangin
g
Inhibition
of ROS
productio
n
Inhibition
of prooxidant

EFFECT

Free radical
Lipid
peroxidation

1) Body cells and tissues are continuously in danger by

the damage caused by free radicals and reactive
oxygen species.
2) which

are

produced

during

normal

oxygen

metabolism.
3) 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.

4) The mechanisms and the sequence of events by

which free radicals interfere with cellular functions
are not fully understood
5) But some of the detrimental effects in biological
systems includes.
a) Peroxidation of membrane lipids,
b) Oxidative damage to nucleic acids or
carbohydrates and
c) The oxidation of sulfhydryl and other
susceptible groups in proteins.
6) 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
ACTIVITY

Modulation of
inflammatory
cell

MECHANIS
M
Modulatio
n of
enzymatic
activity
Modulation
of
Secretory
procesess

EFFECT

Inflammatory
cells
activation

1) 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.
2) The immune response can be modified by
a) Diet
b) pharmacological agents
c) environmental pollutants
d) and naturally occurring food chemicals
such as vitamins and flavonoids.

3) Some
flavonoids
show
a
remarkable
biochemical and pharmacological actions, that
affect
the
function
of
immune
and
inflammatory cells such as
a) T cells,
b) B cells,
c) macrophages,
d) neutrophils,
e) mast cells, or basophils.

4) Several flavonoids specifically affect enzyme

systems critically involved in the generation of
inflammatory processes.
5) especially
tyrosine
and
serine-threonine
protein kinases.
6) These enzymes are involved in signaling
transduction and cell activation processes such
as

a) T cell proliferation,
b) B lymphocyte activation or
c) cytokine production by stimulated
monocytes

Modulation of proinflammatory
enzyme activities
ACTIVITY

Modulation of
proinflammator
y
enzymes

MECHANIS
M
inhibition
of
Arachidoni
c acid
enzyme
inhibition
of NO
synthase

EFFECT

Inflammatory
mediators:
NO,
Leukotrienes,
prostaglandins

1) Many investigations have shown that different

flavonoid molecules modulate the activity of
arachidonic acid metabolizing 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 are mediators of inflammation.
3) 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
ACTIVITY

Modulation of
proinflammator
y mediators

MECHANIS
M

Modulatio
n of
cytokine
production

EFFECT

Inflammatory
Cytokine:
TNF- ,
Interleukines.

1) In addition to COX-2 several cytokines are

deeply
associated
with
inflammatory
diseases
2) In particular, tumor necrosis factor-a (TNFa) is prominent contributors to chronic
inflammatory responses.
3) flavonoids
are
required
for
optimal
inhibition of LPS stimulated TNF-a release.

Modulation of proinflammatory
gene expression
ACTIVITY

Modulation of
proinflammato
ry
gene
expression

MECHANIS
M

Modulatio
n of signal
transducti
on

EFFECT

proinflammator
y
Gene
transcription

1) Several lines of evidence shows that certain

flavonoids are modulators of proinflammatory
gene expression by attenuation of the
inflammatory response
2) It is not known to what extent these
proinflammatory gene expression changes
contribute to the inflammatory response
3) but is evident that flavonoids show antiinflammatory 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
implications in cancer

anti-inflammatory
agents:
and cardiovascular disease

Ana Garca-Lafuente ,Eva Guillamon.

Ana Villares,Mauricio A. Rostagno.
Jose Alfredo Martnez.

The Effects of Plant Flavonoids

Implications for Inflammation,
Cancer

on Mammalian Cells:
Heart Disease, and

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

Thank You