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Friday, May 15, 2009


V. Naveen KumarHH, R. Raju
National College of Pharmacy, Manassery, Calicut

Cite this: V. Naveen Kumar, R. Raju, "FLAVONOIDS AS ANTIOXIDANTS", B. Pharm Projects and Review Articles, Vol. 1, pp. 898-949, 2006. (


    The plants are indispensable to man for his life. The three important necessities of life - food, clothing and shelter - and a host of other useful products are supplied to him by the plant kingdom. Nature has provided a complete store house of remedies to cure all ailments of mankind. The knowledge of drugs has accumulated over thousands of years as a result of man's inquisitive nature so that today we possess many effective means of ensuring health care. Human beings, appear to be afflicted with more diseases than any other animal species. Thus, very early, he sought to alleviate his sufferings from injury and disease by taking advantage of plants growing around him.

    Today, a vast store of knowledge concerning therapeutic properties of different plants has accumulated. All phyla of plants viz. Thallophyta, Bryophyta, Pteridophyta and spermatophyta contain species that yield official and unofficial products of medicinal importance.

    Traditional and Alternative System of medicine like Traditional Chinese medicine and Kampoh system, Ayurveda, Unani, Homeopathic system etc use extracts and tinctures of plants like Ephedra sinica, Rheum palmatum, Panax ginseng, Rauwolfia serpentina, Asparagus racemosus, Aconitum napellus, Colchicum autumnale, Gentian etc. Aroma therapy uses essential oils of basil, eucalyptus, calendula, fennel, garlic, geranium, jasmine, lavender, sandalwood etc. Bach Flower Remedies are prepared from flowers of wild plants, bushes or trees like white chestnut, wild rose, mimulus, chicory, gentian etc.



    The chemical compounds which can delay the start or slow the rate of lipid oxidation reaction in body system. By curbing the activity of free radicals in the body antioxidants can slow down the processes that cause disease and ageing.

    Antioxidants are a broad group of compounds that destroy single oxygen molecules and other Fe3+ also called free radicals in the body thereby protecting against oxidative damage to cells.


    Oxidants or Free radicals can be defined as chemical species possessing unpaired electrons, which are formed by homolytic cleavage of a covalent bond of a molecule by loss of a single electron from a normal molecule or by the addition of a single electron to a normal molecule. Free radicals may be positively charged (cation radical), negatively charged (anion radical) or neutral.

    These free radicals have very short half-life, high reactivity and damaging activity towards macromolecules like proteins DNA and lipids.

    These species may be either oxygen derived reactive oxygen species (ROS) or nitrogen derived reactive nitrogen species (RNS). ROS includes superoxide, hydroxyl, hydroperoxyl, peroxyl, alkoxyl as free radicals and hydrogen peroxide, hypochlorous and ozone and singlet oxygen as non-radicals . RNS are mainly nitric oxide, peroxy nitrile and nitrogen dioxide and dinitrogen trioxide.

    In addition, chlorinated and brominated oxidants (eg. HOCl & HOBr) are enzymatically formed from the interaction between chloride-bromide anions and ROS.

    Free radicals can be formed in 3 ways:
  1. By homolytic cleavage of covalent bond of a normal molecule, with each fragment retaining one of the paired electrons.
  2. By loss of single electron from normal molecule.
  3. By addition of a single electron to a normal molecule.
They are constantly generated in vivo.

Free radicals may be produced by
  1. Ionising radiation
  2. Accidental or deliberate
  3. Some enzymes utilize free radicals at their active sites in the process of catalysis.
  4. Activated phagocytes also deliberately generate free radicals such as super oxide.
  5. These are produced by the leakage of electron transport chain such as those in mitochondria and Endoplasmic reticulum
  6. Metabolites of certain compounds exert toxicity their free radical mechanism eg: CCl4 is metabolized to toxic trichloromethyl free radical by CYP 450 in liver.

Effect of Oxidants on Body Tissue
    Free radical injury and oxidative stress have been implicated in many renal diseases like acute renal failure, IgA nephropathy, anaemia of chronic renal failure and ischaemic kidney.

  • free radicals damage lipids, proteins and DNA
    • selected age related diseases possibly caused by free radical damage: Coronary heart disease, stroke, cancer, arthritis, alzheimers, cataracts, glaucoma, parkinsons disease, muscular dystrophy, multiple sclerosis, cystic fibrosis, schizophrenia
Antioxidants enzymes present in body are:
  1. Glutathione-S-transferase (GST)
  2. Catalase
  3. Glutathione (GSH)
O2 + H2O2 2 H2o + O2



glutathione peroxidase and superoxide dismutase are powerful antioxidants produced by body.


GSH (Glutathione)
    It is a protein that is naturally occurring in the body and protects each cell, tissue and organ from aging cancer and disease. It is an antioxidant, immune booster and detoxifier. It is rapidly consumed in illness and stress and fatigue and diminish with age.

SOD (Superoxide dismutase)
    It is an antiradical enzyme, which help to prevent free radicals from causing cancer or other cell damage in the body. The electrostatic steering effect of the SOD enables it to attract, bind to and deactivate free radical in the human body.

Glutathione Peroxidase

    It is a peroxidase found in the erythrocytes of mammals that helps prevent lipid peroxidation of the cell membrane. The function of glutathione peroxidase, therefore, is to reduce lipid hydroperoxides to their corresponding alcohols and to reduce free H2O2 to water. eg: 2GSH + H2O2 GSSG + 2H2O
GSH ––– reduced monomeric glutathione
GSSG –– oxidised glutathione
Glutathione reductase then reduces the oxidised glutathione to complete the cycle.
Glutathione peroxidase is a selenium containing tetrameric glycoprotein

Some compounds useful as antioxidants are:
Natural antioxidants
  1. Tocopherols
  2. Sesamol
  3. Gossypol
  4. Vitamins: vitamin C, vitamin A, folic acid
  5. selenium, zinc, manganese

Synthetic antioxidants
  1. Butylated Hydroxy Anisole (BHA), Butylated Hydroxy Toluene (BHT), Propyl Gallate (PG) and Tertiary Butyl Hydroquinone (TBHQ)
     Metal chelators: phosphoric acid, citric acid, ascorbic acid, EDTA.

Glutathione-S-transferase (GST)

    GST is a family of enzymes comprising a list of cytosolic, mitochondrial and microsomal proteins which are capable of multiple reactions with multitude of substrates, both endogenous or xenobiotic. GSTs contribute to the phase II biotransformation of xenobiotics by conjugating these compounds with reduced glutathione to facilitate dissolution in aqueous cellular and extra cellular media and from there, out of the body.
    GSTs catalyse conjugation of reduced glutathione via the sulfhydryl group, to electrophilic centres on a wide variety of substrates. This activity is useful in the detoxification of endogenous compounds such as peroxidised lipids as well as metabolism of xenobiotics.


    Human erythrocyte catalase – its function include catalysing the decomposition of H2O2 to water and oxygen. It is a tetramer of 4 polypeptide chains.
    2H2O2      2H2O +O2

Mechanisms of Antioxidants
  1. Hydrogen donation to free radicals by antioxidants
  2. Formation of a complex between the lipid radical and the antioxidant radical (free radical acceptor)
  3. Metal chelation

Reaction of antioxidants with radicals
R. + AH RH + A.
RO. + AH ROH + A.
R. + A. RA
RO. + A. ROA
Antioxidant + O2 Oxidised antioxidant

    If a compound inhibits the formation of free alkyl radicals in the initiation step, or if the chemical compound interrupts the propagation of the free radical chain, the compound can delay the start or slow the chemical reaction rate of lipid oxidation.

    The initiation of free radical formation can be delayed by the use of metal chelating agents, singlet oxygen inhibitors and peroxide stabilizers.

    The propagation of free radical chain reaction can be minimised by the donation of hydrogen from the antioxidants and the metal chelating agents.

    The major antioxidants currently used in foods are monohydroxy or poly hydroxy phenol compounds with various ring substitutions. These compounds have low activation energy to donate hydrogen. The resulting antioxidant free radical does not initiate another free radical due to the stabilization of delocalization of radical electron.

    The resulting antioxidant free radical is not subject to rapid oxidation due to its stability. The antioxidant free radicals can also react with lipid free radicals to form stable complex compounds.


    Flavonoids are polyphenolic compounds possessing fifteen carbon atoms, two benzene rings joined by a linear three carbon chain.


6 subgroups: Chalcones, Flavone, Flavonol, Flavonone,. Anthocyanins, Isoflavonoid.
Examples of flavonoids: Rutin, Hesperidin, Kaempherol, Liquiritin, Isoliquiritin, Myricetin, Quercetin, Naringin.

Mechanism of Action

    Flavonoids exert their antioxidant effects (countering inflammatory, bacterial, viral, microbial, hormonal, carcinogenic, neoplastic and allergic disorders) by neutralizing all types of oxidising radicals including the super oxide and hydroxyl radicals and by chelation. A chelator binds to metal ions in our bodies to prevent them from being available for oxidation. Also they inhibit oxidation enzymes in cells.

    Flavonoids also act as powerful chain breaking antioxidants due to the electron donating capacity of their phenolic groups.

    Flavonoids reduce the oxidation of low density lipoproteins and also prevent platelet aggregation by inhibiting the activity of the enzyme cyclooxygenase


Some of the models used to study Antioxidant Activity
In-vivo models:
    Glucose - oxidase induced inflammation in paw of mouse
Carrageenan – induced paw edema in rat
Endotoxin – treated animals (mouse)
Zymosan – induced arthritis in mouse
Acetic acid – induced colitis in rat
Skin reactions to histamine in rat
Kainate induced brain injury in rat
CCl4 – induced liver damage in rat
In these experimental models, ROS are involved in the induction and development of the inflammatory response.

In-vitro models
  1. Conjugated diene assay
    During linoleic acid oxidation, the double bonds are converted into conjugated double bonds, characterized by strong UV absorption at 234nm
  1. DPPH method (1,1-diphenyl-2-picryl hydrazyl)
    Based on the reduction of methanolic solution of coloured free radical, DPPH by free radical scavenger.
  1. Super oxide radical scavenging activity
  2. Hydroxyl radical scavenging activity
  3. Nitric oxide radical inhibition activity
  4. Reducing power method
  5. Phospho molybdenum method
  6. Peroxy nitrile radical scavenging activity
  7. ABTS method (2,2-azinobis (3-ethyl benzothiazoline -6-sulfonic acid diamonium salt)
  8. DMPD (N,N-dimethyl p-phenylene diamine dihydrochloride) method
  9. Oxygen Radical Absorbance Capacity (ORAC)
  10. b-carotene linoleate model
  11. Xanthine Oxidase method
  12. FRAP method (Ferric Reducing Ability of Plasma)
  13. TRAP method (Total Radical trapping Antioxidant Parameter)
  14. Cytochrome C Test
  15. Erythrocyte ghost system
  1. Microsomal lipid peroxidation/Thiobarbituric acid assay (TBA assay)
Sources of Flavonoids

    Tea is a very potent source of antioxidative flavonoids such as Cathechins, Theaflavin and Trearubin. Green tea has more simple flavonoids called Catechins. Black tea contains more complex falvonoids called Threaflavins and thearubigins.

The main sources of super antioxidants (flavanoids) can be found in:
Pycnogenol or French maritime pine bark extract
Blue berries
Grape seed extract
Tea and red wine


  1. Cytotoxicity and Lipid peroxidation inhibiting activity of flavonoids.
-Cos P et al
Thirty-five flavonoids of seven different types, namely isoflavonoids, chalcones, dihydroflavonols, flavanols, flavonones, flavones and flavonols were investigated for their activity to inhibit ascorbate induced microsomal lipid peroxidation and their cytotoxicity. For each activity, a structure-activity relationship was established.

    Subsequently, an antioxidant selectivity index ie the maximal non-toxic dose divided by the IC50 value for lipid peroxidation was introduced.

    Kaempherol showed the highest antioxidant selectivity index of all flavanoids tested.

  1. Antioxidant activities of flavidin in different in vitro model systems.
-Jayaprakasha GK et al
    Flavidin was isolated from orchidaceae species and purified by silica gel column chromatography. The structure was identified by physical and spectral (1H, 13C NMR & Mass) data. Antioxidant potency of flavidin was investigated employing various established invitromodel systems. b-carotene linoleate, 1,1-diphenyl-2-picryl hydrazyl (DPPH), phosphomolybdenum method and scavenging of hydrogen peroxide methods. Flavidin showed very good antioxidant activity (90.2%) and almost equivalent to that of BHA at 50 ppm level by b-carotene linoleate method. Radical scavenging activity of flavidin was compared with BHA at 5, 10, 20 and 40 ppm concentration and flavidin showed more radical scavenging activity than BHA at all the tested concentration. Further more, Flavidin showed very good antioxidant capacity by the formation of phosphomolybdenum complex method. Besides this flavidin showed effective hydrogen peroxide scavenging activity.

    The data obtained in the invitro models clearly establish the antioxidant potency of flavidin.

  1. Aqueous extracts of Teucrium polium possess remarkable Antioxidant activity in Vitro.
-Ljubuncic P et al
    Teucrium polium is a medicinal plant used in traditional medicine for its diuretic, diaphoretic, tonic, antipyretic, antispasmodic and cholagogic properties. The therapeutic benefit is often attributed to this antioxidant properties.

    It has been previously reported that an aqueous extract of the leaves and stems of this plant could inhibit iron-induced lipid peroxidation in rat liver homogenate. Others have reported that organic extracts of the aerial components of this plant could inhibit oxidative processes.

    In this paper (i) its ability to inhibit
(a) Oxidation of b-carotene
(b) 2,2-azobis (2-amidino propan) dihydro chloride (AAPH) induced plasma oxidation.
(c) Iron-induced lipid peroxidation in rat liver homogenates
ii) to scavenge superoxide radical and hydroxyl radical
iii) effect on enzyme xanthine oxidase activity
iv) capacity to bind iron
v) its effect on cell glutathione (GSH) homeostasis in cultured Hep G2 cells were investigated.
It was found that the extract
(i) inhibited
(a) oxidation of b-carotene
(b) AAPH-induced plasma oxidation
(c) Fe2+ - induced lipid peroxidation in rat liver homogenates
(ii) scavenged super oxide radical and hydroxyl radical
(iii) bound free iron
(iv) tended to increase GSH levels resulting in a decrease in the GSSG/GSH ratio.

  1. Apple phytochemicals and their health benefits.
-Boyer J, Liu RH
    The purpose of this paper is to review the most recent literature regarding health benefits of apples and their phytochemicals, phytochemical bioavailability and antioxidant behaviour and effects of variety, ripening, storage and processing on apple phytochemicals.

    Apples contain a variety of phytochemicals, including quercetin, catechin, phloridzin and chlorogenic acid, all of which are strong antioxidants. Major class of phytochemicals present are flavonoids. Phytochemical composition varies greatly with varieties. Storage has no effect but processing affects the phytochemicals small changes occur due to ripening and maturation. .

Health benefits and apples: Animal and in vitro studies
Antioxidant activity
    Apples and apple peels showed potent antioxidant activity and can greatly inhibit the growth of liver cancer and colon cancer cells. Some of the most well- studied antioxidant compounds in apples-quercetin-3-galactoride, quercetin-3-glucoside, coumaric acid, chlorogenic acid, gallic acid and phloridzin.

    The compounds most commonly found in apple peels; procyanidins catechin, epicatechin, chlorogenic acid, phloridzin and quercetin conjugates. Quercetin conjugates are found exclusively in peels. Because, the apple peels contain more antioxidant compounds especially, quercetin, apple peels may have higher antioxidant activity and higher bioactivity than the apple flesh.

    It was found that rats consuming apple peels showed greater inhibition of lipid peroxidation and greater plasma antioxidant capacity when compared to rats fed apple flesh.

    The procyanidins epicatechin and catechin have strong antioxidant activity and have been found to inhibit LDL oxidation in vitro. Sawa et al (1999) found that chlorogenic acid has very high allyl peroxyl radical (Roo.) scavenging activity. Since Roo may enhance tumor promotion and carcinogenesis, chlorogenic acid may add to the protective effect of apples against cancer.

    Quercetin is also a strong antioxidant. Quercetin has protected Caco-2 cells from lipid peroxidation induced by H2O2 and Fe2+. In mice liver treated with ethanol, quercetin decreased lipid oxidation and increased glutathione protecting the liver from oxidative damage.

Anti proliferative activity
    When Caco-2 colon cancer cells were treated with apple extracts cell proliferation was inhibited in a dose-dependent manner reaching a maximum inhibition of 43% at a dose of 50 mg/mL. Same trend was seen in Hep G2 liver cancer cells with maximal inhibition reaching 57% at a dose of 50mg/mL. Apples without peels were significantly less effective in inhibiting Hep G2 cell proliferation.



Inhibition of lipid oxidation
    Addition of apple phenolics to human serum decreased diphenyl-hexatriene labelled phosphatidyl choline (DPHPC) oxidation in a dose-dependent manner. DPHPC is an indicator of oxidation incorporated in LDL, HDL and VLDL fractions. It also led to a decrease in albumin DPHPC oxidation.
  1. Chemical constituents and their antioxidant activity of stem of Rhododendron mucronulatum.
-Lee JH et al
    From the n-BuOH soluble fraction of the 70% aqueous acetone extract of Rhododendron mucronulatum stem, 12 compounds were isolated on the basis of spectral data, they were identified as:
i) Scopoletin    ii) (+) – taxifolin    iii) quercetin    iv) (–) – catechin      v) (+) – epicatechin    vi) scopolin     vii) lyoniside    viii) srioriside    ix) fraxin x) (+) – lyoniresinol-3-alpha-0-beta-o-glucopyranoside        xi) (+) – taxifolin-3-0-alpha-L-arabinopyranoside    xii) astragalin respectively.

    All isolated compounds were tested antioxidant activity against 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical. Compounds (2) and (3) showed the potent antioxidant activity. (5), (8) and (11) showed moderate activity.         

  1. Protective effects of grape seed proanthocyanidins against oxidative stress induced by lipopolysaccharides of periodontopathogens.
-Houde V et al
Background: During phagocytosis or stimulation with bacterial components, macrophages activate various cell processes, including the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which are critical for successful defense against invading organisms. Increased levels of ROS/RNS create oxidative stress that results in tissue and bone destruction. Grape seed proanthocyanidins have been reported to possess a wide range of biologic properties against oxidative stress. In the present study, the effects of a grape seed proanthocyanidin extract (GSE) and commercial polyphenols on the production of ROS and RNS and on the protein expression of inducible nitric oxide synthase (INOS) by murine macrophages stimulated with lipopolysaccharides (LPS) of periodontopathogens were investigated.

Methods: Macrophages (RAW 264.7) were treated with non-toxic concentrations of either GSE or commercial polyphenols (gallic acid [GA] and [-]- epigallocatechin-3-gallate [EGCG]) and stimulated with LPS of Actinobacillus actinomycetemcomitans or Fusobacterium nucleatum, and iNOS expression was evaluated by immunoblotting. Nitric oxide (NO) production was quantified using the colorimetric Griess assay, whereas ROS production was measured with the fluorescent 123 dihydroohodamine dye.

Results: GSE strongly decreased NO and ROS production and iNOS expression by LPS stimulated macrophages. GA also revealed a strong inhibitory effect on NO production without affecting iNOS expression h\but slightly increasing ROS production. EGCG showed an inhibitory effect on NO and ROS production and on iNOS expression by macrophages.

  1. Antioxidant and antiradical activities in extracts of hazelnut kernel (Corylus avellana L.) and hazelnut green leafy cover.
-Alasalvar C et al
    Phenolic compounds in the aqueous systems were extracted, from hazelnut kernel (HK) and hazelnut green leafy cover (HGLC), with 80% (v/v) ethanol (HKe and HGLCe) or 80% (v/v) acetone (HKa and HGLCa). The extracts were examined for their phenolic and condensed tannin contents and phenolic acid profiles (free and esterified fractions) as well as antioxidant and antiradical activities by total antioxidant activity (TAA), antioxidant activity in a beta-catotene-linoleate model system, scavenging of DPPH (2,2-diphenyl-1- picrylhydrazyl) radical, and reducing power. Significant differences (p < 0.05) in the contents of total phenolics, condensed tannins, and TAA existed among the extracts that were examined. HGLCa extract had the highest content of total phenolics (201 mg of catechin equivalents/g of extract), condensed tannins (524 mg of catechin equivalents/g of extract), and TAA (1.29 mmol of Trolox equivalents/g of extract) followed by HGLCe, HKa, and HKe extracts, respectively. Five phenolic acids (gallic acid, caffeic acid, p-coumaric acid, ferulic acid, and sinapic acid) were tentatively identified and quantified, among which gallic acid was the most abundant in both free and esterified forms. The order of antioxidant activity in a beta-catotene-linoleate model system, the scavenging effect on DPPH radical, and the reducing power in all extracts were in the following order: HGLCa > HGLCe > HKa > HKe. These results suggest that both 80% ethanol and acetone are capable of extracting phenolics, but 80% acetone was a more effective solvent for the extraction process. HGLC exhibited stronger antioxidant and antiradical activities than HK itself in both extracts and could potentially be considered as an inexpensive source of natural antioxidants.

  1. Major flavonoids in grape seeds and skins: antioxidant capacity of catechin, epicatechin, and gallic acid.
-Yilmaz Y, Toledo RT
    Grape seeds and skins are good sources of photochemicals such as gallic acid, catechin, and epicatechin and are suitable raw materials for the production of antioxidative dietary supplements. The differences in levels of the major minomeric flavanols and phenolic acids in seeds and skins from grapes of Vitis cinifera varieties Merlot and Chardonnay and in seeds from grapes of Vitis rotundifolia variety Muscadine were determined, and the antioxidant activities of these components were assessd. The contribution of the major monomeric flavonols and phenolic acid to the total antioxidant capacity of grape seeds and skins was also determined. Gallic acid, monomeric catechin, and epicatechin concentrations were 99, 12, and 96 mg/100 g of dry matter (dm) in Muscadine seeds, 15, 358, and 421 mg/ 100 g of dm in Chardonnay seeds, and 10, 127, and 115 mg/100 g of dm in Merlot seeds, respectively. Concentrations of these three compounds were lowr in winery byproduct grape skins than in seeds. These three major phenolic constituents of grape seeds contributed <26% to the antioxidant capacity measured as ORAC on the basis of the corrected concentrations of gallic acid, catechin, and epicatechin in grape byproducts. Peroxyl radical scavenging activities of phenolics present in grape seeds or skins in decreasing order were resveratrol > catechin > epicatechin = gallocatechin > gallic acid = ellagic acid. The results indicated that dimeric, trimeric, oligomeric, or polymeric procyanidins account for most of the superior antioxidant capacity of grape seeds.

  1. Relevance of apple polyphenols as antioxidants in human plasma: contrasting in vitro and in vivo effects.
-Lotito SB, Frei B
    Apples are a major source of flavonoids in the Western diet, and flavonoid-rich foods may help protect against chronic diseases by antioxidant mechanisms. In the present study was investigated:
  1. the antioxidant capacity of representative apple polyphenols and their contribution to the total antioxidant capacity of apple extracts;
  2. the effects of adding apple extract to human plasma in vitro on oxidation of endogenous antioxidants and lipids;
  3. the effects of apple consumption by humans on ex vivo oxidation f plasma antioxidants and lipids. We found that the apple contained flavonols and flavanols, quercetin, rutin, (-)-epicatechin, and (+)-catechin, had a higher antioxidant capacity than the dihydrochalcones, phloridzin and phloretin, and the hydroxycinnamate, chlorogenic acid. However, together these apple polyphenols contributed less than 20% to the total antioxidant capacity of aqueous apple extracts. When human plasma was exposed to a constant flux of aqueous peroxyl radicals, endogenous ascorbate was oxidized within 45 min of incubation, while endogenous urate and alpha-tocopherol were oxidized after ascorbate. Addition of 7.1 or 14.3 micrograms/ml total phenols of apple extract did not protect ascorbate from oxidation, but increased the half-life (t1/2) of urate from 136 +/– 15 to 192 +/–16 and 208 +/– 23 min, respectively and t1/2 of alpha-tocopherol from 141 +/– 18 to 164 +/– 8 min and 188 +/– 8 min . Lipid peroxidation started after ascorbate depletion, and addition of apple extract increased the lag time preceding detectable lipid peroxidation from 36.3 +/– 3.7 to 50.9 =/– 2.7 min and 70.4 +/– 4.2 min.

  1. Identification and characterization of antioxidants from Sophora flavescens.
-Piao XL et al
    The objectives of this study were to investigate the radical-scavenging activity and protective potential of Sophora flavescens from oxidative damage by the radical generator 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) in renal epithelial LLC-PK(1) cells and to identify the active components using the bioassay-linked fractionation method. The MeOH extract and fractions of CH(2) Cl(2), BuOH, and H(2)O from S. flavescens showed 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging effects in a dose-dependent manner, whereas only the BuOH and CH(2) Cl(2) fractions showed protective effects against LLC-PK(1) cellular damage induced by AAPH in a dose-dependent manner. In particular, the BuOH fraction had the most effective antioxidative capacity. Employing a bioassay linked HPLC/MS method, the active constituents from the BuOH fraction of S. flavescens were isolated and characterized as sophoraflavanone G and kurarinone with potent antioxidant effects against the DPPH radical, with IC(50) values of 5.26 and 7.73 microg/ml, respectively. Moreover, the compounds dose dependently recovered cell viability decreased by AAPH treatment suggesting their protective roles against cellular oxidative damage. The results of this study suggest that S. flavescens has excellent antioxidative and kidney-protective potential and that flavonoids from S. flavescens, i.e, sophoraflavanone G and kurarinone, are the active constituents.

  1. Protective effects of the flavonoids Osajin and Pomiferin on heart ischemia-reperfusion.
-Necas J et al
    The study was undertaken to evaluate the cardioprotective potential of the flavonoids osajin and pomiferin against ischemia-reperfusion induced injury in rat hearts as a model of antioxidant-based composite therapy. Studies were performed with isolated, modified Langendorff perfused rat hearts and ischemia of the heart was initiated by stopping the coronary flow for 30 min followed by 60 min of reperfusion. Wistar rats were divided into four groups. The treated groups received osajin or pomiferin (5 mg/kg/day in 0.5% Avicel), the placebo group received only 0.5 Avicel; the intact group was left without any applications. Biochemical indicators of oxidative damage--malondialdehyde, superoxide dismutase, glutathione peroxidase, total antioxidant activity in serum and the myocardium have been evaluated. Also examined the effect of osajin and pomiferin on cardiac function: left ventricular end-diastolic pressure, left ventricular pressure, and peak positive dp/dt. The results demonstrate that the flavonoids osajin and pomiferin attenuate the myocardial dysfunction provoked by ischemia-reperfusion. This was confirmed by an increase in both the antioxidant enzyme values and the total antioxidant activity. The cardioprotection provided by osajin and pomiferin treatment results from the suppression of oxidative stress and correlates with the improved ventricular function.

  1. Antioxidant properties of various solvent extracts of total phenolic constituents from three different agroclimatic origins of drumstick tree (Moringa oleifera Lam.) leaves.
-Siddhuraju P, Becker K
    Water, aqueous methanol, and aqueous ethanol extracts of freeze-dried leaves of Moringa oleifera Lam. From different agroclimatic regions were examined for radical scavenging capacities and antioxidant activities. All leaf extracts were capable of scavenging peroxyl and superoxyl radicals. Similar scavenging activities for different solvent extracts of each collection were found for the stable 1,1-diphenyl 2-picrylhydrazyl (DPPH(*) radical. Among the three different moringa samples, both methanol and ethanol extracts of Indian origins showed the highest antioxidant activities, 65.1 and 66.8%, respectively, in the beta-carotene-linoleic acid system. Nonetheless, increasing concentration of all the extracts had significantly increased reducing power, which may in part be responsible for their antioxidant activity. The major bioactive compounds of phenolics were found to be flavonoid groups such as quercetin and kaempferol. On the basis of the results obtained, moringa leaves are found to be a potential source of natural antioxidants due to their marked antioxidant activity. Overall, both methanol (80%) and ethanol (70%) were found to be the best solvents for the extraction of antioxidant compounds from moringa leaves.

  1. Flavonoids as superoxide scavengers and antioxidants.
-Chen YT et al
    The superoxide anions scavenging activity and antioxidation of seven flavonoids--quercetin, rutin, morin, acacetin, hispidulin, hesperidin, and naringin--were studied. The superoxide anions were generated in a phenazin methosulphate NADH system and were assayed by reduction of nitroblue tetrazolium. The scavenging activity ranked: rutin was the strongest, and quercetin and naringin the second, while morin and hispidulin were very weak. The concentration values yielding 50% inhibition of lipid peroxidation in mouse liver homogenate were in order of 10(-6) M for quercetin, rutin, and morin; and of 10(-5) M for acacetin and hispidulin, while naringin and hesperidin had no antioxidative action.

  1. Reduction in free-radical-induced DNA strand breaks and base damage through fast chemical repair by flavonoids
– Anderson RF et al
    This paper provides evidence that dietary flavonoids can repair a range of oxidative radical damages on DNA, and thus give protection against radical induced strand breaks and base alterations. Dilute aqueous solutions of plasmid DNA were irradiated in the absence and presence of flavonoids (F) in a "constant OH radical scavenging environment", K of 1.5 ´ 10 (7) S (–1) by decreasing the concentration of TRIS buffer in relation to the concentration of added flavonoids. It was shown that the flavonoids can reduce the incidence of single strand breaks in double-stranded DNA as well as residual base damage by a mechanism other then through direct scavenging of *OH radicals. Pulse radiolysis measurements support the mechanism of electron transfer or H* atom transfer from the flavonoids to free radical sites on DNA which result in the fast chemical repair of some of the oxidative damage on DNA resulting from *OH radical attack.


  1. Cytotoxicity, genotoxicity and Oxidative reactions in cell-culture models: modulatory effects of phytochemicals
– O'Brien NM et al
    The aim of the study was to determine if flavonoids could protect against H2O2 - induced DNA damage, as measured by the comet assay, in CaCO-2 and HepG2 cells. Both cell lines were supplemented with increasing concentrations of myricetin, quercetin and rutin for 24 hours followed by exposure to H2O2 (50 microM) for 30 minutes. Exposure to H2O2 for 30 min at 37 degrees C resulted in significant DNA damage and pre incubation with the flavonoids before H2O2 exposure significantly protected CACO-2 and HepG2 cells against H2O2 - induced DNA damage.

  1. Protective effect of natural flavonoids on rat peritoneal macrophages injury caused by asbestos fibers
– Kostyuk VA et al
    Exposure of macrophages to asbestos fibers results in enhancement of the production of oxygen radicals, determined by a lucigenin enhanced chemiluminescence (LEC) assay, a formation of thiobarbituric acid reactive substances (TBARS), a LDH release into the incubation mixture and a rapid lysis of the cells. Rutin (Rut) and quercetin (Qr) were effective in inhibiting LEC, TBARS formation and reducing peritoneal macrophages injury caused by asbestos. Both flavonoids were found to be oxidized during exposure of peritoneal macrophages to asbestos and the oxidation was SOD sensitive. The efficacy of flavonoids as antioxidant agents as well as superoxide ion scavengers was also evaluated using appropriate model systems, and both quercetin and rutin were found to be effective in scavenging O2.

  1. In vivo effect of diosmin on carrageenan and CCl4 - induced lipid peroxidation in rat liver microsomes
– Melin AM et al
    The aim of this study was to compare the protective effect of a flavonoids, the 3', 5, 7 - trihydroxy-4'-methoxy flavone 7-rutinoside or diosmin, on liver microsomal lipid peroxidation induced in rats by either carbon tetrachloride or carrageenan. Thirty rats were divided into five groups. Group 1 received no chemical product and was considered as control. Groups 2 and 3 received either an intraperitoneal injection of carrageenan or carbon tetrachloride 48 or 24 hours before killing, respectively. Groups 4 and 5 were treated first with an intraperitoneal injection of diosmin and then by carrageenan (group 4) or carbon tetrachloride (group 5) 48 or 24 hours before killing, respectively. The lipoperoxidant effect of carrageenan and CCl4 was demonstrated by both significant decreases in polyunsaturated fatty acids, and of vitamin A in groups 2 and 3. With diosmin treatment only TBARS significantly decreased in group 4 whereas vitamin A level increased.

  1. Phytochemical characterization and radical scavenger activity of flavonoids from Helichrysum italicum (compositae)
– Facino RM et al
    The glycosidic fraction of the flavonoids extracted from the flowering tops of Helichrysum italicum was isolated, purified and characterized. This fraction was constituted by three compounds which were assigned the structure of 4, 2', 4', 6' - tetrahydroxy chalcone - 2' - glucoside, kaempferol - 3 - glucoside and naringenin - glycoside. Radical scavenger properties of the single glycosyl - glavonoids and in toto glycosidic fraction were tested with in vitro systems where different reactive oxygen species are generated (superoxide ions, hydroxyl radicals) and on lipid peroxidation induced by ADP/Fe2+ and NADPH or CCl4 in rat liver microsomes. The formation of reactive oxygen species was detected by cytochrome C reduction, salicylic acid hydroxylation and hyaluronic acid depolymerization. The glycosidic fraction inhibited in a dose dependent fashion lipid peroxidation in rat liver microsomes treated with ADP/Fe2+ or CCl4. This effect is due to the ability of flavonoids to scavenge free radicals at different stages of the process (super oxide ions, hydroxyl and lipid peroxide radicals). The single glycosyl-flavonoids exhibited a different scavenger activity, depending on the oxygen species and the chemical structure of the compounds.

  1. Antioxidant activity of nasunin, an anthocyanin in egg plant
– Noda Y et al
    Nasunin was isolated from egg plant peels, solanum melongena using an electron spin resonance spectrometer and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) spin trapping, hydroxyl (.OH) or super oxide anion radicals (O2*–) generated by the Fenton reaction or the hypoxanthine-xanthine oxidase system were, measured as DMPO-OH or DMPO-OOH spin adducts. Nasunin directly scavenged O2*– and inhibited formation of DMPO-OH. A spectrophotometric study showed that nasunin formed an iron complex with a molar ratio of nasunin: Fe3+ of 2:1. Therefore, hydroxyl radical scavenging by nasunin is due to inhibition of .OH generation by chelating iron. Nasunin (1micro M) significantly protected against lipid peroxidation of brain homogenates as measured by malonaldehyde and 4-hydroxyalkenals.

  1. Protective effect of flavonoids on endothelial cells against linoleic acid hydroperoxide - induced toxicity
– Kaneko T, Baba N
    The protective effect of flavonoids against linoleic acid hydroperoxide (LOOH) - induced cytotoxicity was examined by using cultured endothelial cells. When the cells were incubated with both LOOH and flavonoids, most flavonols protected the cells from injury by LOOH. Flavones bearing an ortho-dihydroxy structure also showed a protective effect. Flavonones had no effect. The interaction between flavonoids and a-tocopherol was also examined in this system. Flavonoids that were protective against LOOH - induced cytotoxicity had at least an additive effect on the action of alpha-tocopherol against LOOH - induced damage.

  1. On the ability of four flavonoids, baicilein, luteolin, naringenin and quercetin, to suppress the Fenton reaction of the iron-ATP complex
– Cheng IF, Breen K
    Four flavonoids, baicilein, luteolin, naringenin, and quercetin were investigated for their ability to suppress the Fenton reaction characteristic of the iron-ATP complex.

    Absorption spectroscopy indicates that under the conditions of 18.75% aqueous methanol, 0.0625 mM HEPES pH 7.4 buffer and 1.5:1 quercetin/iron-ATP ratio a mix ligand complex formed. All four flavonoids were found to interfere with the voltammetric catalytic wave associated with the iron-ATP complex in the presence of H2O2. Quercetin and luteolin were able to completely suppress the catalytic wave of the iron-ATP/H2O2 system when a minimum ration of 1.5:1 of the flavoloid to iron-ATP was reached. At this ratio, the ability of the flavonoids to suppress the Fenton reaction characteristic of iron-ATP follows as quercetin approximate to luteolin>naringenin approximate to baicilein.

  1. Study of antioxidant effect of apigenin, luteolin and quercetin by DNA protective method.
– Romanova D et al
    A DNA protective capacity of three flavonoids, apigenin (AP), luteolin (LU) and quercetin (QU) against free radicals generated by H2O2, resp. Fe2+is reported. This effect corresponding with scavenging of free radicals or with chelating of iron was assayed at two concentrations of flavonoids studied (1 microM and 10 microM). The quantitative analysis has shown that LU possesses the highest DNA protective effect of flavonoids investigated in the presence of H2O2. On the other hand in the presence of 10 microM Fe2+, AP exhibited the highest DNA protective effect at the concentration of 1 microM and the following order was reached at the stoichiometric concentrations (10 microM) of Fe2+. It id believed that this discrepancy is caused by the ability of LU and QU iron-complex formation as it was separately investigated using UV-VIS spectrometry.

  1. Interactions of flavonoids with iron and copper ions: a mechanism for their antioxidant acivity.
– Mira L. et al
    The metal chelating properties of flavonoids suggest that they may play a role in metal overload diseases and in all oxidative stress conditions involving a transition metal ion. A detailed study has been made of the ability of flavonoids to chelate iron (including Fe3+) and copper ions and its dependence of structure and pH. The acid medium may be important in some pathological conditions. In addition, the ability of flavonoids to reduce iron and copper ions and their activity-structure relationships were also investigated. To fulfill thse objectives, flavones (apigenin, luteolin, kaempferol, quercetin, myricetin and rutin), isoflavones (daidzein and genistein), flavanones (taxifolin, naringenin and naringin) and a flavanol (catechin) were investigated. All flavonoids studied shown higher reducing capacity for copper ions than for iron ions. The flavonoids with better Fe3+ reducing activity are those with a 2,3-double bond and possessing both the catechol group in the B-ring and the 3-hydroxyl group. The copper reducing activity seems to depend largely on the number of hydroxyl groups. The chelation studies were carried out by means of ultraviolet spectroscopy and electrospray ionization mass spectrometry. Only flavones and the flavanol catechin inteact with metal ions. At pH 7.4 and pH 5.5 all flavones studied appear to chelate Cu2+ at the same site, probably betweent he 5-hydroxyl and the 4-oxo groups. Myricetin and quercetin, however, at pH 7.4, appear to chelate Cu2+ additionally at the ortho-catechol group, the chelating site for catechin with Cu2+ at pH 7.4. Chelation studies of Fe3+ to flavonoids wre investigated only at pH 5.5. Only myricetin and quercetin interact strongly with Fe3+, complexation probably occurring again between the 5-hydroxyl and the 4-oxo groups. Their behaviour can be explained by their ability to reduce Fe3+ at pH 5.5, suggesting that flavonoids reduce Fe3+ to Fe2+ before association.

  1. Different antioxidant activities of bioflavonoid rutin in normal and iron-overloading rats.
– Afanas'ev IB et al
    The effects of rutin on liver microsomes, peritoneal macrophages, and blood neutrophils isolated from iron-overloading (IOL) and normal rats were studied. The formation of 2-thiobarbituric acid-reactive products and the level of lucigenin-amplified chemiluminescence (CL) were determined in liver microsomes. Oxygen radical production by phagocytes was measured by luminal-and lucigenin-amplified CL and superoxide dismutase-sensitive cytochrome c reduction. These ex vivo findings were compared with the in vitro effects of rutin on cellular free processes. It was found that rutin administration sharply suppressed free radical production in liver microsomes and by phagocytes of IOL animals and only slightly affected these processes in normal rats. The selective inhibitory effect of rutin under pathologic conditions induced by iron overload is thought to be due to the formation of inactive iron-rutin complexes which are unable to catalyse the conversion of superoxide ion into reactive hydroxyl radicals, a process responsible for the free radical-mediated toxic effects of iron overload. These findings may account for the favourable effects of the treatment of pathologies associated with iron overload with rutin.

  1. Chelating and free radical scavenging mechanisms of inhibitory action of rutin and quercetin in lipid peroxidation.
– Afanas'ev IB et al
    Inhibitory effects of flavonoids rutin and quercetin on ferrous ion-dependent lipid peroxidation of lecithin liposomes and NADPH-and CCl4-dependent lipid peroxidation in rat liver microsomes were studied to elucidate the chlating and free radical scavenging activities of these compounds. The interaction of rutin with superoxide ion and ferrous ions and the reaction of quercetin with lipid peroxy radicals were also studied. Both flavonoids were significantly more effective inhibitors of iron ion-dependent lipid peroxidation systems due to chelating iron ions with the formation of inert iron complexes unable to initiate lipid peroxidation. At the same time, iron complexes of flavonoids retained their free radical scavenging activities. The chelating mechanism of inhibition was more important for rutin than for quercetin. The mutual effect of rutin and ascorbic acid on non-enzymatic lipid peroxidation was also studied. It was concluded that rutin and quercetin are able to suppress free radical processes at three stages: the formation of superoxide ion, the generation of hydroxyl radicals in the Fenton reaction and the formation of lipid peroxy radicals.

  1. Lipid antioxidant properties of quercetin in vitro
– Das M, Ray PK
    The effect of quercetin on iron-catalyzed hepatic microsomal lipid peroxidation was investigated. Quercetin was shown to be a potent inhibitor of iron-induced lipid peroxidation with a I50 of 0.2 mM. The inhibitory effects of quercetin were dependent on incubation time, protein concentration and iron content in the incubation mixture. Since quercetin dose not interact with malonyl-aldehyde it can be concluded that the inhibition of iron induced lipid peroxidation is due to lipid antioxidant property and this may serve as a model for the study by which "free" iron may initiate peroxidation in vivo.




    The aim of this literature review was to study and establish the antioxidant potency of flavonoids.

    Flavonoids are polyphenols present as phytochemicals in fruits, leaves, flowering tops, roots etc.

    The antioxidant properties of flavonoids have been found to be responsible for the therapeutic benefit of many medicinal plants used in traditional medicine. For example, investigators have reported that the aerial parts of Teucrium polium are rich in flavonoids (27, 28).

    Polyphenolic compounds present in fruits like apples produce a wide variety of effects that may help prevent chronic disease (4).

    The data obtained in invitro models like b-carotene linoleate, DPPH, Phosphomolybdenum method etc clearly establish the antioxidant potency of flavonoids (2, 7, 12).

    Grape seed extract which has powerful antioxidant activity against NO and ROS is a rich source of flavonoids, namely procyanidins (6, 8). The kidney-protective potential of the flavonoids sophoraflavanone G and kurarinone from sophora flavescens and the cardioprotection provided by Osajin and Pomiferin treatment results from the suppression of oxidative stress (10, 11). Dietary flavonoids can repair a range of oxidative radical damages on DNA by mechanisms other than direct scavenging of *OH radicals; that is by electron transfer or H* atom transfer to free radical sites on DNA (14). Flavonoids Quercetin and Rutin have been found to be effective in scavenging superoxide radicals (13, 16). Ability of flavonoids like Quercetin, luteolin, naringenin to inhibit or suppress free-radical generating pathways like Fenton reaction have been proved (21). Both quercetin and luteolin contain catechol on the B ring, which may enhance the iron chelation. The 4-keto, 5-hydroxy region also contribute to the chelation of iron. The structure activity relationship revealed the presence of either the ortho-di-hydroxy structure in the B ring of the flavonoids or 3-hydroxyl and 4-oxo groups in the C ring to be important for the protective activities of flavonoids.

    It has also been found that the flavonoids rutin and quercetin are able to suppress free radical processes at three stages; the formation of superoxide ion, the generation of hydroxyl radicals in the Fenton reaction and the formation of lipid peroxy radicals.


    The facts and data collected through this literature review point to the conclusion that flavonoids possess potent antioxidant activity and can be used for the treatment of diseases arising out of free-radical generation.


  1. Cytotoxicity and Lipid peroxidation inhibiting activity of flavonoids
    – Cos P, Calomme M, Sindambiwe J.B, De Bruyne T, Cimanga K, Pieters L,     Vliktinck AJ, Vanden Berghe D
    Planta Med. 2001 Aug; 67 (6): 515-9.

  1. Antioxidant activities of flavidin in different in vitro model systems.
    – Jayaprakasha GK, Jaganmohan Rao L, Sakariah KK
    Bioorg Med Chem. 2004 Oct 1; 12 (19): 5141-6

  1. Aqueous extracts of Teucrium polium possess remarkable Antioxidant activity in vitro
    – Ljubuncic P, Dakwar S, Portnaya I, Cogan U, Azaizeh H, Bomzon A Evid     Based Complement Alternat Med. 2006 Sep; 3 (3): 329-38. Epub 2006
    Jun 20.

  1. Apple phytochemicals and their health benefits
    – Boyer J, Liu RH
    Nutr J. 2004 May 12; 3:5

  1. Chemical constituents and their antioxidant activity of stem of Rhododendron mucronulatum.
    – Lee JH, Jeon WJ, Yoo E.S, Kim C.M, Kwon YS
    Natural Product Sciences, V. 11 (2): p. 97-102, 2005 (Eng; 24 ref).

  1. Protective effects of grape seed proanthoujanidins against oxidative stress induced by lipopolysaccharides of periodontopathogens.
    – Houde V, Grenier D, Chandad F
    J Periodontol. 2006 Aug; 77 (8): 1371-9.
  1. Antioxidant and antiradical activities in extracts of hazelnut kernel (Corylus avellana L) and hazelnut green leafy cover.
    – Alasalvar C, Karamac M, amarowiez R, Shahidi F
    J Agric Food Chem. 2006 Jun 28; 54 (13): 4826-32.

  1. Major flavonoids in grape seeds and skins: antioxidant capacity catechin, epicatechin, and gallic acid
    – Yilmaz Y, Toledo RT.
    J Agric food Chem. 2004 Jan 28; 52 (2): 255-60.

  1. Relevance of apple polyphenols as antioxidants in human plama: Contrasting in vitro and in vivo effects.
    – Lotito SB, Frei B.
    Free Radic Biol Med. 2004 Jan 15; 36 (2): 201-11.

  1. Identification and characterization of antioxidants from sophora flavescens.
    – Piao XL, Piao XS, Kim SW, Park JH, Kim HY, Cai SQ.
    Biol Pharm Bull. 2006 Sep; 29 (9): 1911-5.

  1. Protective effects of the flavonoids osajin and pomiferin on heart ischemia-reperfusion.
    – Necas J, Bartosikova L, Florian T, Klusakova J, Suchy V, Naggar EM,     Janostikova E, Bartosik T, Liskova M.
    Ceska Slov Farm. 2006 Jul; 55 (4): 168-74.

  1. Antioxidant properties of various solvent extracts of total phenolic constituents from three different agroclimativ origins of drumstick tree (Moringa oleifera Lam.) leaves.
    – Siddhuraju P, Becker K
    J Agric food Chem. 2003 Apr 9; 51 (8): 2144-55


  1. Flavonoids as superoxide scavengers and antioxidants
    – Chen YT, Zheng RL, Jia ZJ, Ju Y.
    Free Radic Biol Med. 1990; 9 (1): 19-21.

  1. Reduction in free radical-induced DNA strand breaks and base damage through fast chemical repair by flavonoids.
    – Anderson RF, Amarasinghe C, Fisher LJ, Mak WB, Packer JE.
    Free Radic Res. 2000 Jul; 33 (1): 91-103.

  1. Cytotoxicity, genotoxicity and oxidative reactions in cell-culture models: modulatory effects of phytochemicals
    – O'Brien NM, Woods JA, Aherne SA, O'Callaghan YC
    Biochem Soc Trans. 2000 Feb; 28 (2): 22-6

  1. Protective effect of natural flavonoids on rat peritoneal macrophages injury caused by asbestos fibers
    – Kosyuk VA, Potaporich AI, Speransky SD, Maslova GT
    Free Radic Biol Med. 1996; 21 (4): 487-93.

  1. In vivo effect of diosmin on carrageenan and CCl4-induced lipid peroxidation in rat liver microsomes
    – Melin AM, Perromat A, Clerc M.
    J Biochem Toxicol. 1996; 11 (1): 27-32

  1. Phytochemical characterization and radical scavenger activity of flavonoids from Helichrysum italicum G. Don (compositae)
    – Facino RM, Carini M, Franzoi L, Pirola O, Bosisio E.
    Pharmacol Res. 1990 Nov-Dec; 22 (6): 709-21

  1. Antioxidant activity of nasunin, an anthocyanin in egg plant.
    – Noda Y, Kaneyuki T, Igarashi K, Mori A, Packer L.
    Res Commun Mol Pathol Pharmacol. 1998 Nov; 102 (2): 175-87.
  1. Protective effect of flavonoids on endothelial cells against linoleic acid hydroperoxide-induced toxicity
    – Kaneko T, Baba N.
    Biosci Biotechnol Biochem. 1999 Feb; 63 (2): 323-8

  1. On the ability of four flavonoids, baicilein, luteolin, raringenin and quercetin, to suppress the Fenton reaction of the iron-ATP complex.
    – Cheng IF, Breen K
    Biometals. 2000 Mar; 13 (1): 77-83.

  1. Study of antioxidant effect of apigenin, luteolin and quercetin by DNA protective method.
    – Romanova D, Vachalkova A, Cipak L, Ovesna Z, Rauko P
    Neoplasma 2001; 48 (2): 104-7

  1. Interactions of flavonoids with iron and copper ions: A mechanism for their antioxidant activity
    – Mira L, Fernandez MT, Santos M, Rocha R, Florencio MH, Jennings KR
    Free Radic Res. 2002 Nov; 36 (11): 1199-208.

  1. Different antioxidant activities of bioflavonoid rutin in normal and iron-overloading rats.
    – Afanas'ev IB, Ostrachovitch EA, Abramova NE, Korkina LG.
    Arch Biochem Biophys. 1998 Jul 1; 355 (1): 43-8

  1. Chelating and free radical scavenging mechanisms of inhibitory action of rutin and quercetin in lipid peroxidation.
    – Afanas'ev IB, Dorozhko AI, Brodskii AV, Kostyuk VA, Potapovitch AI.
    Biochem Pharmacol. 1989 Jun 1; 38 (11): 1763-9


  1. Lipid antioxidant properties of quercetin in vitro – Das M, Ray PK. Biochem Int. 1988 Aug; 17 (2): 203-9

  1. A Chemotaxonomic Study of Flavonoids from European Teucrium Species.     – Harborne JB, Tomas B, Williams CA, Gil MI. Phytochemistry 1986; 25: 2811-6

  1. Iridoids and Flavonoids of Teucrium polium herb – Rizk AM, Hammouda FM, Rimpler H, Kamel A Planta Med. 1986; 2: 87-8.



Cite this: V. Naveen Kumar, R. Raju, "FLAVONOIDS AS ANTIOXIDANTS", B. Pharm Projects and Review Articles, Vol. 1, pp. 898-949, 2006. (

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