This document summarizes a student presentation on the roles of flavonoids in human health. It discusses the sources of flavonoids, their structure, biosynthesis pathway, and various pharmacological activities including antioxidant, cardio-protective, anti-carcinogenic, gastro-protective, anti-microbial, anti-inflammatory, and anti-thrombotic effects. It provides examples of specific flavonoids and their effects. The presentation concludes that flavonoids show therapeutic potential but their use requires validation through biochemical testing, and their safety depends on appropriate dosing.

1. BABCOCK UNIVERSITY
COLLEGE OF HEALTH AND MEDICAL SCIENCES
BENJAMIN S. CARSON (SNR) SCHOOL OF MEDICINE
DEPARTMENT OF BIOCHEMISTRY
2014/2015 ORAL SEMINAR PRESENTATION (BCHM 433)
ROLES OF FLAVONOIDS IN HUMAN HEALTH
KOLAWOLE, KAYODE DANIEL (11/3269)
BIOCHEMISTRY, 400L
SUPERVISOR: PROFESSOR O.O. ADEBAWO
30TH OCTOBER, 2014.

2. FLAVONOIDS
 Flavonoids, formally called vitamin P (are not
really vitamins but possess vitamin-like properties)
are phytochemicals or a sub-class of polyphenols
that are found to be beneficial to human health.
 Due to the variety of pharmacological activities in
the mammalian body, flavonoids may also be
referred as “nutraceuticals” (Tapas et al., 2008)

3. Flavonoid Biosynthesis
Figure 2: Schematic representation of flavonoid
biosynthesis pathway (Hummer et al., 2008)

4. Figure 1: Basic structure of flavonoids (Bimlesh et al., 2011)

5. Sources of Flavonoids
Flavonoids are ubiquitous in
photosynthesising cells and
are commonly found in
• fruits,
• vegetables,
• nuts,
• seeds,
• stems, flowers, tea, wine,
propolis and honey (Tim
and Andrew, 2005).

6. Table 1: Classification of some flavonoids and their common sources
(Mukesh et al., 2005)
Chemical Class` Example Major Dietary Source
Flavonol Quercetin, Rutin, Myricetin,
Kaempferol
Tea, Red wine, Apple,
Tomato, Cherry and Onion
Flavanols Catechin, Gallocatechin Tea and Apple
Flavones Apigenin, Luteolin, Chrysin Thyme and Parsley
Isoflavones Genistein, Glycitein,
Formononetin, Daidzein
Soya bean and other
legumes
Flavanones Hesperidin, Narigenin Grape fruit and Orange
Flavanonols Taxifolin Lemon and sour orange

7. Pharmacology of Flavonoids
 Flavonoids have been reported to exert a wide
range of biological activities. These include:
• Antioxidant Activity
• Cardio-protective effects
• Anti-carcinogenic effects
• Gastro-protective effects
• Treatment of Inflammation
• Antimicrobial effects, and many more.

8. Antioxidant activity
 Oxidative damage could lead to a lot of degenerative
diseases such as artherosclerosis, hypertension, cataracts
etc. which occurs when the electron flow generates free
radicals, such as O2- centred free radicals, known as
reactive oxygen species (ROS), and including superoxide
(O2˙¯), peroxyl (ROO˙), alkoxyl (RO˙), hydroxyl (HO˙)
and nitric oxide (NO˙) radicals (Hamdoon., 2009).
 Indeed, the phenolic groups of flavonoids serve as a
source of a readily available ‘‘H” atoms such that the
subsequent radicals produced can be delocalized over the
flavonoid structure (Tripoli et al., 2007).

9. Figure 3: Scavenging capacity of free radicals (R.) (Bimlesh et al., 2011)
Figure 4: Formation of peroxy Radical (Bimlesh et al., 2011)

10. Cardio-Protective Effects
Table 2: Proposed positive effects of flavonoids on CVS (Bimlesh et
al., 2011)
S/N Cardiovascular diseases Influence of Flavonoids
1 Artherosclerosis Decrease in LDL oxidation by LOX inhibition and attenuation of oxidative
stress, inhibition of leucocyte leucocyte adhesion, myeloperoxidase,
decreased expression of iNOS and COX-2.
2 Arrhythmia Decrease in oxidative stress.
3 Acute Myocardial infarction Decrease in ROS burst, inhibition of platelet aggregation
4 Heart Failure
Decrease in oxidative stress (direct ROS scavenging) inhibition of
metalloproteinase
5 Hypertension
Vasodilatory properties, inhibition of NADPH oxidase, recovery of NO due
to inhibition of superoxide production

11. Anti-Carcinogenic Effects
 Flavonoids are potent bioactive molecules that
possess anti-carcinogenic effects since they can
interfere with the initiation, development and
progression of cancer by the modulation of cellular
proliferation, differentiation, apoptosis, angiogenesis
and metastasis (Ramos, 2007).
 Some molecular mechanisms of action of
flavonoids are given as follows:
• cell cycle arrest (p53 proteins),
• tyrosine kinase inhibition,
• inhibition of heat shock proteins.

12. Figure 5: Multistage of carcinogenesis and potential effects
of polyphenols on cancer progression (Ramos, 2007)

13. Gastro-protective Effects
 The mechanism of action responsible for the anti-ulcer
activity of flavonoids is their antioxidant
properties, seen in garcinol, rutin and quercetin.
 It involves free radical scavenging, transition metal
ions chelation, inhibition of oxidizing enzymes,
increase of proteic and nonproteic antioxidants and
reduction of lipid peroxidation (Mohamed and Azza,
2011).

14. Anti-microbial Effects
 Anti-fungal activity
• A number of moulds and yeasts cause human and animal
diseases. For example, species of Aspergillus, Fusarium,
and Sporothrix are opportunistic pathogens and easily infect
individuals with weak immune systems.
• An isoflavone found in a West African legume, alpinum
isoflavone, prevents schistosomal infection when applied
topically.
• Amentoflavone from Selaginella tamariscina (Spikemoss)
exhibited potent antifungal activity (IC50 value of 18.3 mg/ml)
against several pathogenic fungal strains and has a very low
haemolytic effect on human erythrocytes
(Jung et al., 2006).

15.  Anti-Bacterial Effects
• Antibacterial flavonoids having sugar moiety form
complexes with proteins by forming either covalent
bond, hydrogen bond or hydrophobic effects.
• Their mode of action may be related to their ability
to inactivate microbial adhesions, cell envelope
transport proteins and others. (Bimlesh et al., 2011).
• Quercetin has been reported to completely inhibit
growth of Staphylococcus aureus (Tapas et al., 2008).

16.  Anti-Viral Effects
• The mechanism of antiviral action of polyphenolic
compounds is based on their abilities to act as
antioxidants, to inhibit enzymes, to disrupt cell
membranes, to prevent viral binding and penetration
into cells, and to trigger the host cell self-defense
mechanisms (Mendel, 2007).
• A recent area of research that is of particular interest
is the apparent inhibitory activity of flavonoids
(luteolin) against human immunodeficiency virus
(HIV) (Andrew and Tim, 2005)

17. • The HIV-1 transactivator of transcription (Tat)
protein engages positive transcription elongation
factor b (pTEFb) complex (cycT1 and CDK9),
increasing RNA pol II activity and driving viral
transcriptional elongation.
• To a large extent, the introduction of combination
antiretroviral treatment (cART) has curtailed viral
replication below the detection limit (<50
copies/mL) and significantly reduced the devastating
impact of HIV-1.
(Mehla et al., 2011)

18. • These three flavonoids
are found to be nontoxic
and have anti-HIV-1
activity.
• Luteolin was the most
potent and inhibited
HIV-1 infection by
abrogating Tat-mediated
LTR activity.
Figure 6: Inhibition of HIV-1 by flavonoids (Mehla, 2011)

19. Anti-Inflammatory Effects of Flavonoids
 Inflammation is a normal biological process in response to
tissue injury, microbial pathogen infection, and chemical
irritation.
 In general, normal inflammation is rapid and self-limiting, but
aberrant resolution and prolonged inflammation cause various
chronic disorders (Pan et al., 2010).
 Flavonoids are able to inhibit expression of isoforms of
inducible nitric oxide synthase, cyclooxygenase, and
lipooxygenase, which are responsible for the production of a
great amount of nitric oxide, prostanoids, leukotrienes, and
other mediators of the inflammatory process such as
cytokines, chemokines, or adhesion molecules (Tunon et al.,
2009).

20. Anti-thrombotic Activity of Flavonoid
Arachidonic acid released by inflammatory
conditions is metabolized by platelets to form
prostaglandin, endoperperoxides and thromboxane
A2 thus contributing to platelet activation and
aggregation.
Platelet aggregation further contributes to
atherosclerosis and acute platelet thrombus
formation.
The main antiaggregatory effect of flavonoid is by
the inhibition of thromboxane A2 formation.
(Bimlesh et al., 2011)

21. Flavonoid RDA (Recommended Dietary
Allowance)
There are no official dosages for bioflavonoids.
Doses in most supplements sold range from 30 to
200 milligrams a day which is acceptable for general
maintenance.
Clinical trials tend to be based on much higher doses
of between 500 to 2000 mg (milligrams). For
therapeutic purposes the range can be between 50 to
500 mg per day.
(Health Supplements Nutritional Guide, 2009)

22. Toxicological Profile of Flavonoids
With the exception of green tea, research on flavonoids
in general shows no known toxic effects. High doses do
not appear to cause serious side effects, even for
amounts as high as 100 grams a day. Excess intake is
simply excreted in urine.
The main symptom of flavonoid overdose is diarrhea.
As for green tea, highly concentrated doses of it might
contain too much caffeine for cancer and hepatitis
patients, and for those people sensitive to caffeine.
(Health Supplements Nutritional Guide, 2009)

23. Conclusion
Structure function relationship of flavonoids is
epitome of major biological activities.
Medicinal efficacy of many flavonoids as
antibacterial, hepatoprotective, anti-inflammatory,
anticancer, and antiviral agents is well established.
Therapeutic use of new compounds must be
validated using specific biochemical tests.

24. Further achievements will provide newer insights
and will certainly lead to a new era of flavonoid
based pharmaceutical agents for the treatment of
many infectious and degenerative diseases.
Remember:
“DOSAGE DETERMINES TOXICITY”

26. References
• Bimlesh K., Prashant T., Manoj S., Pardeep S., and Harleen S.
(2011). A Review of Phytochemistry and pharmacology of
Flavonoids. Internationale Pharmaceutica Scientia, 1 (1): 25-
38.
• Hamdoon A.M. (2009). Natural and synthetic flavonoid
derivatives with potential Antioxidant and Anticancer
Activities. published thesis, 16.
• Http://WWW.HealthSupplementNutritionalGuide.Org.
Retrieved 28th september, 2014.
• Jung, H.J., Sung, W.S., Yeo, H.S., Kim H.S., Lee, I.S., Woo,
E.R., and Lee D.G. (2006). Arch. Pharm. Research. 29:746.

27. • Mehla, R., Bivalkar-Mehla, S., Chauhan, A. (2011). A
Flavonoid, Luteolin, Cripples HIV-1 by Abrogation of Tat
Function. PLoS ONE 6(11): e27915.
doi:10.1371/journal.pone.0027915
• Mendel, Friedman (2007). Overview of antibacterial,
antitoxin, antiviral, and antifungal activities of tea flavonoids
and teas. Mol. Nutr. Food Res., 51: 116-134.
• Mohamed, Morsy and Azza, El-Sheikh, (2011). Prevention of
gastric ulcers, peptic ulcer disease,Dr.Jianyuan Chai (Ed), 456
Pp; ISBN: 978-953-307-976-9, Intech, DOI: 10.5772/17942.
• Mukesh Nandave, S. Ojha, D. Arya (2005). Protective role of
flavonoids in cardiovascular diseases. Natural Product
Radiance, 4(3): 166- 176.

28. • Pan M., S. Lai, and C. Ho (2010). Anti-inflammatory activity of natural
dietary flavonoids, Food and Function, 1(1): 15–31.
• Ramos, S. (2007). Effects of dietary flavonoids on apoptic pathways related
to cancer chemoprevention. Journal of Nutritional Biochemistry, 18: 427-
442.
• Tapas, A.R., Sakarkarl,D.M., and Kakde, R.B. (2008). Flavonoids as
Nutraceuticals: A Review. Tropical Journal of Pharmaceutical Research,
7(3): 1089–1099.
• Tim-Cushnie T.P, and Andrew J. (2005). Antimicrobial activity of
flavonoids. International Journal of Antimicrobial Agents, 26: 343-356.
• Tunon, M., M. Garcia-Mediavilla, S. Sanchez-Campos, and J. Gonzalez-
Gallego (2009). “Potential of flavonoids as antiinflammatory agents:
modulation of pro-inflammatory gene expression and signal transduction
pathways. Current Drug Metabolism, 10(3): 256–271.