Flavonoids overview

1. Flavonoids
Kaustav Dey
M. Pharm (Pharmacognosy) 1st Sem
University Institute of Pharmaceutical Sciences
Panjab University

2. Contents
1. What are flavonoids ?
2. Distribution
3. Nomenclature
4. Properties
5. Classification
6. Different types of flavonoids
7. Medicinal & Health benefits
8. Extraction
9. Chemical Tests

3. Flavonoids
 Secondary metabolite
 Derived from word flavus meaning yellow color
 Non - nitrogenous universal plant pigment
 Discovered by Hungarian Biochemist Albert Szent-Gyorgi (1938)
 Flavonoids are the largest groups (<20,000) of the naturally occurring phenols.
 These are described as compounds with a C6-C3-C6 carbon skeleton (15 C-atoms)
 Molecular formula – 2-phenyl chromen-4-one ; Phenyl benzopyran

4.  Biosynthesis – Phenylpropanoid pathway
 Starting material - 4-coumaroyl-CoA
 Important enzymes needed for biosynthesis - Chalcone synthase,
flavanone 3-hydroxylase, dihydroflavonol 4-reductase, anthocyanidin
reductase.
 Benefits - nutraceutical, pharmaceutical, medicinal and cosmetic
applications.
 Therapeutic properties - anti-oxidative, anti-inflammatory, anti-
mutagenic and anti-carcinogenic properties coupled with their capacity
to modulate key cellular enzyme function.

5.  Biochemical and antioxidant effects associated with various
diseases such as cancer, Alzheimer’s disease (AD), atherosclerosis, etc
 Inhibitors for several enzymes, such as xanthine oxidase (XO) cyclo-
oxygenase (COX), lipoxygenase and phosphoinositide 3-kinase
 Plant Benefits - used by vegetables for their growth and defense
against plaques.
 Flavonoids protect plants from different biotic and abiotic stresses
and act as unique UV filters(10) , function as signal molecules,
allopathic compounds, phytoalexins, detoxifying agents and
antimicrobial defensive compounds

6. Distribution of Flavonoids
 Absent in algae except member of Charophyceae (green algae)
 Present in Fungi – Chloroflavonin and Dihydrochalkone (Aspergillus
candidus)
 Present everywhere in higher plants
 Found throughout the Gymnosperms and Angiosperms
 Within plants they are present in every part of the plant.
○ Fruits – Berries, Grapes, Apple, Bell peppers, Citrus Fruits
○ Beans – Soyabeans , Legumes
○ Leaves – Tea, Gingko
○ Flowers
○ Roots & Rhizomes – Glycyrrhiza (Mulethi)
○ Stem & its modifications - Onion

7. Nomenclature
1. Systematic system
○ It is based on the chemical structure and IUPAC naming of the compound
○ Complex to use
○ Example- 2,3-Dihydro-2-phenyl-4H-1-benzopyran-4-one
2. Semi-systematic system
○ In this system, flavonoids are named in such a manner that it represent the
subgroup or the types of the flavonoid
○ Most common and more easy and simple to use
○ Example- Flavanone

8. 1. Trivial system
○ Largely on the basis of the name of the source from where they
are isolated
○ In this system ,the nomenclature is done in such a way that its
name indicates its structures
○ Flavonoids with suffix:
○ - 'nidin' indicates Anthacyanidin e.g., - Pelargonidin
○ - 'etin' indicates flavonol type e.g.-Quercetin
○ This method lacks consistency in naming and it was difficult to
adhere to this system

9. 4. Semi-trivial system
○ These names are obtained by modifying the trivial name of a
parent structure (e.g. Chrysin) with a systematic or semi
systematic modifier, e.g., to arrive at the name 8-Prenyl-chrysin.
○ Not used in mainstream due to problems like duplicacy and
ambiguity as the parent structure may have more than one
trivial name and severe difficulties in documentation

10. Properties of Flavonoids
 Occur in both aglycone and glycosidic (O- and C-glycosides) form
 Mostly are monomeric (e.g.- kaempferol) , but dimeric and oligo- or
polymeric structures (proanthocyanidins) are also known.

11. Properties of Flavonoids
Wide Solubility Pattern
 Aglycones: Dichloromethane, Ethylacetate (medium polarity solvent)
 Glycones: Methanol, Ethanol or Hydroalcoholics (more polar solvent)
 Catechins: Water

12. Classification of Flavonoids
 Flavonoids can be classified on the basis of :
○ Saturation of ring C
○ Position of ring B (most prevalent)
○ Molecular weight (least used)

13. Classification of Flavonoids – Saturation of Ring C
 When ring C is saturated

14. Classification of Flavonoids – Saturation of Ring C
 When ring C is unsaturated
○ Flavones
○ Flavonols
○ Isoflavones
○ Anthocyanidins

15. Classification of Flavonoids – Position of Ring B
 Simple Flavonoids (Ring B attached to 2nd position of Ring C)
 Iso-flavonoids (Ring B attached to 3rd position of Ring C)
 Neo-flavonoids (Ring B attached to 4th position of Ring C)

16. Classification of Flavonoids – Position of Ring B
Simple Flavonoids
 Also known as 2-Phenylbenzopyran
 Flavans (flavan-3-ol; flavan-4-ol;
flavan-3,4-diol)
 Flavanones
 Flavanols (dihydro flavonol)
 Flavones
 Flavonols

17. Classification of Flavonoids – Position of Ring B
Isoflavonoids
 Also known as 3-Phenyl
benzopyran
 Isoflavan
 Isoflavone
 Isoflavanones
 Isoflavanol

18. Classification of Flavonoids – Position of Ring B
Neoflavonoids
 Also known as 4-Arylbenzopyran
 4-ary; coumarins
 3,4-dihydro-4-aryl coumarin
 Neoflavene
Minor flavonoids
Chalcones
 No heterocyclic ring but a open ring
system
 Benzopyran nucleus is absent
 Precursor for other flavonoids

19. Different Types of Flavonids
 Anthocyanins (Pelargonidin, Delphinidin)
○ Found in Fruits, red wine, cereals, leafy & root vegetables.
 Proanthocyanidins & Luecoanthocyanidins
 Flavones (Luteolin, Apigenin)
○ Found in aromatic herbs like parsley, celery, garlic, green peppers, chamomile tea
and some cereals such as millet and wheat.
 Flavonols (Kaempferol, Quercetin, Rutin)
○ Found in Onions , broccoli, blueberries, red wine and tea.

20. Different Types of Flavonids
 Flavanones & Flavanonols (Hesperidin, Naringenin)
○ Found in tomatoes, oranges, lemons, mandarins, mint.
 Bi-flavonoids (Theasinensin A, Amentoflavone)
 Iso-Flavonoids (Gentisin, Diadezin)
○ Found in leguminous plants, soya.
 Neo-Flavonoids (Dalbergichromene)
 Chalcones (Carthamin) & Aurones (Sulefretin)
○ Found in apples, pears, apricots, red wine, green tea, chocolate.
 Rotenoids (Rotenone)
 Pterocarpans (Pisatin)

23. Flavonols
 Flavonols are flavonoids with a ketone group.
 They are building blocks of proanthocyanins.
 Flavonols occur abundantly in a variety of fruits and vegetables.
 The most studied flavonols are kaempferol, quercetin, myricetin.
 Onions, kale, lettuce, tomatoes, apples, grapes tea, red wine and berries
are rich sources of flavonols.
 Intake of flavonols is found to be associated with a wide range of health
benefits which includes antioxidant potential and reduced risk of
vascular disease.

24. Flavanones
 Flavanones are another important class which is generally present in
all citrus fruits such as oranges, lemons and grapes.
 Hesperitin, naringenin and eriodictyol are examples of this class of
flavonoids.
 Flavonones are associated with a number of health benefits because
of their free radical scavenging properties.
 These compounds are responsible for the bitter taste of the juice
and peel of citrus fruits.

25. Isoflavonoids
 Isoflavonoids are a large and very distinctive subgroup of flavonoids.
 Isoflavonoids enjoy only a limited distribution in the plant kingdom
and are predominantly found in soyabeans and other leguminous
plants.
 Some isoflavonoids have also been reported to be present in
microbes to play an important role as precursors for the
development of phytoalexins during plant microbe interactions .
 Isoflavonoids exhibit tremendous potential to fight a number of
diseases.

26. Neoflavonoids
 Neoflavonoids are a class of polyphenolic compounds.
 While flavonoids have a 2-phenylchromen-4-one backbone,
neoflavonoids have a 4-phenylchromen backbone with no hydroxyl
group substitution at position 2.
 The first neoflavone isolated from natural sources in 1951 was
calophyllolide from Calophyllum inophyllum seeds.
 It is also found in the bark and timber of the Sri Lankan endemic plant
Mesua thwaitesii .

27. Flavanols, flavan-3-ols or catechins
 Flavanols, also called dihydroflavonols or catechins, are the 3-hydroxy
derivatives of flavanones.
 They are a highly diversified and multisubstituted subgroup.
 Flavanols are also referred to flavan-3-ols as the hydroxyl group is always
bound to position 3 of the C ring.
 Unlike many flavonoids, there is no double bond between positions 2 and 3.
 Flavanols are found abundantly in bananas, apples, blueberries, peaches and
pears

28. Anthocyanins
 Anthocyanins are pigments responsible for colours in plants,
flowers and fruits.
 Cyanidin, delphinidin, malvidin, pelargonidin and peonidin are the
most commonly studied anthocyanins .
 They occur predominantly in the outer cell layers of various fruits
such as cranberries, black currants, red grapes, merlot grapes,
raspberries, strawberries, blueberries, bilberries and blackberries.
 Stability coupled with health benefits of these compounds facilitate
them to be used in the food industry in a variety of applications .

29. Chalcones
 Chalcones are a subclass of flavonoids.
 They are characterised by the absence of ‘ring C’ of the basic
flavonoid skeleton structure.
 Hence, they can also be referred to as open-chain flavonoids.
 Major examples of chalcones include phloridzin, arbutin, phloretin
and chalconaringenin.
 Chalcones occur in significant amounts in tomatoes, pears,
strawberries, bearberries and certain wheat products.

30. Medicinal &
Health Benefits
of Flavonoid

32. Flavonoids as antioxidants
 The best described and most useful property of almost every group of
flavonoids is their capacity to act as antioxidants.
 The flavones and catechins seem to be the most powerful flavonoids
for protecting the body against reactive oxygen species (ROS).
 Flavonoids can prevent injury caused by free radicals in various ways.
One way is the direct scavenging of free radicals.
 Flavonoids are oxidized by radicals, resulting in a more stable, less-
reactive radical.

33. Anti atherosclerotic effects
 Atherosclerosis is a condition that results from the gradual build-up of
fatty substances, including cholesterol, on the walls of the arteries.
 This build-up, called plaque, reduces the blood flow to the heart, brain
and other tissues and can progress to cause a heart attack or stroke.
 An elevated plasma low density lipoprotein (LDL) concentration is a
primary risk factor for the development of atherosclerosis and
coronary artery disease.
 Flavonoids seems to suppress LDL oxidation and inflammatory
progression in the artery wall.

34. Anti platelet aggregation effects
 Platelet adhesion and subsequent aggregation contributes to both the
development of atherosclerosis and acute platelet thrombus
formation, followed by embolization of constricted arteries.
 The main anti aggregatory effect of flavonoids is thought to be by
inhibition of thromboxane A2 formation.
 In vitro studies showed that flavonoids bind to platelet membranes
and may therefore have an accumulative effect over time.

35. Anti Ulcer effect
 A peptic ulcer is an ulcer of an area of the gastrointestinal tract that is
usually acidic and thus extremely painful.
 Majority of peptic ulcers are associated with helicobacter pylori, a
bacterium that lives in the acidic environment of the stomach.
 Quercetin seems to play a very important role in the prevention and
treatment of peptic ulcer.
 It acts by promoting mucus secretion, thereby serves as gastroprotective
agent, also quercetin has been shown to inhibit the growth of
helicobacter pylori bacterium in in-vitro studies

36. Hepatoprotective Activity
 Several flavonoids such as catechin, apigenin, quercetin, naringenin,
rutin, and venoruton are reported for their hepatoprotective activities.
 Silymarin , a flavonolignan, has been reported to stimulate enzymatic
activity of DNA-dependent RNA polymerase 1 and subsequent
biosynthesis of RNA and protein, resulting in DNA biosynthesis and cell
proliferation leading to liver regeneration only in damaged livers
 Several clinical investigations have shown the efficacy and safety of
flavonoids in the treatment of digestive complaints, such as sensation
of fullness, loss of appetite, nausea, and abdominal pain.

37. Anti-bacterial activity
 Flavonoids are known to be synthesized by plants in response to
microbial infection; thus it should not be surprising that they have
been found in vitro to be effective antimicrobial substances against a
wide array of microorganisms.
 Flavonoid rich plant extracts from different species have been
reported to possess antibacterial activity.
 Several flavonoids including apigenin, galangin, flavone and flavonol
glycosides, isoflavones, flavanones, and chalcones have been shown
to possess potent antibacterial activity

38. Anti-inflammatory Activity
 Inflammation is a normal biological process in response to tissue
injury, microbial pathogen infection, and chemical irritation.
 A number of flavonoids such as hesperidin, apigenin, luteolin, and
quercetin are reported to possess anti-inflammatory and analgesic
effects. Flavonoids may affect specifically the function of enzyme
systems critically involved in the generation of inflammatory
processes, especially tyrosine and serine-threonine protein
kinases.

39. Anti-cancer Activity
 Dietary factors play an important role in the prevention of cancers.
 Fruits and vegetables having flavonoids have been reported as
cancer chemo preventive agents.
 Consumption of onions and/or apples, two major sources of the
flavonol quercetin, is inversely associated with the incidence of
cancer of the prostate, lung, stomach, and breast.

40. Anti-cancer Activity
Major molecular mechanisms of action of flavonoids are given as
follows:
 (1) down regulation of mutant p53 protein,
 (2) cell cycle arrest,
 (3) tyrosine kinase inhibition,
 (4) inhibition of heat shock proteins,
 (5) estrogen receptor binding capacity,
 (6) inhibition of expression of Ras proteins

42. Extraction of Flavonoids
Petroleum ether or hexane
• Column chromatography
• Centrifugally assisted preparative
chromatography
• Preparative HPLC
• Flash chromatography

43. Chemical Tests
Name of Test Procedure Inference
Shinoda Test
To the alcoholic extract add Mg
turnings and conc. HCl
Orange to red color
indicates presence of
flavonoids
Zinc Test
To the alcoholic extract add Zn
turnings and conc. HCl
Deep red color
indicates presence of
dihydro-flavonoids
Ammonia Test
Dip a strip of filter paper in
alcoholic extract of the plant
and expose it to ammonia
vapors
Yellow color of paper
strip indicates
flavonoids
Vanillin HCl
Test
Vanillin-HCl solution is added to
alcoholic extract of plant
Pink color indicates
flavonoids

44. References
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45. Thank You