This article throws light upon the top eleven biological effects of flavonoids. The effects are: 1. CNS Activity 2. Cardio-tonic Activity 3. Lipid Lowering Activity 4. Antiulcer Activity 5. Hepato-protective Activity 6. Antioxidant Activity 7. Effect on Heat Shock Proteins 8. Anti-Inflammatory Activity 9. Antineoplastic Activity 10. Effects on Blood Vessels 11. Antimicrobial Activity.
Biological Effect # 1. CNS Activity:
Some synthetic flavonoids possess anxiolytic like properties similar or superior to that of diazepam (Griebel et al., 1999). e.g. 6-bromoflavone and 6-bromo-3′-nitro- flavones, latter is very potent than 6-bromofIavone.
Biological Effect # 2. Cardio-tonic Activity:
Flavonoids are having cardio-protective effects (Huesken et al., 1995). The un-substituted parent flavone exerts coronary dilatory activity and its combination with rutin and iso-quercetin is useful in the treatment of atherosclerosis. 3-methyl quercetin has positive chronotropic effect on guinea pig right atrium and antiarrhythmic effect on left atrium (Lackeman et al., 1986).
In recent report the cardio-toxicity (negative inotropic effect) of doxorubicin on the mouse left atrium has been inhibited by flavonoids, 7-mono-hydroxy ethyl rutoside and 7, 3′, 4′- tri-hydroxyethyl rutoside.
The glycosides of luteolin, apigenin and genistein produced antihypertensive activity even more than the reference drug papaverine. Three flavonoids showed vasorelaxant effect in order of potency, luteolin > eriodictyol > naringenin on rat thoracic aorta.
Quercetin is having stronger inotropic responses among the different flavonoids. The relative order of potency of the tested flavonoids is, quercetin > morin = kaempferol > luteolin = apigenin > fisetin = galangin (Itoigawa et al., 1999).
Biological Effect # 3. Lipid Lowering Activity:
Oxidative modification of low-density lipoproteins (LDL) by free radicals is an early event in the pathogenesis of atherosclerosis. A number of mechanisms are likely to contribute to inhibition of LDL oxidation by flavonoids.
Flavonoids may directly scavenge some radical species by acting as chain breaking antioxidants (De-Whalley et al., 1990). In addition, they may recycle other chain- breaking antioxidants such as a-tocopherol by donating a hydrogen atom to the tocopheryl radical (Francel et al., 1993).
Transition metals such as iron and copper are important pro-oxidants, and some flavonoids can chelate divalent metal ions, hence preventing free radical formation.
The ability of quercetin, and the quercetin glycosides, to protect LDL against oxidative modification has shown a significant protective effect (Mc Anlis et al., 1997). Liquiritigenin showed a significant fall in serum cholesterol, LDL-cholesterol and atherogenic index.
Biological Effect # 4. Antiulcer Activity:
Some recent reports have indicated that many flavonoids possess antiulcerogenic activity, a Hydroxy ethyl rutosides, gossypin, naringin, naringenin and (+)-Cyanidanol-3 were shown to exhibit anti-ulcer activity (Parmar & Shikha Parmar, 1998). Quercetin, rutin and kaempferol administered intraperitoneally (25- 100 mg/kg) inhibited dose-dependent gastric damage produced by acidified ethanol in rats.
Flavone was inactive while naringin was active at a higher dose (200 mg/kg). Lorenz et al, 1973 showed that (+) – Cyanidanol-3 has histidine decarboxylase inhibitory activity and hence anti-ulcer activity.
3-Methoxy-5,7,3′,4′-tetra hydroxy flavan (Meciadanol), a congener of (+)- cyanidanol-3 exhibited significant anti-ulcer activity in pylorus ligated rats, restraint ulcers and gastric mucosal damage induced by aspirin models (Parmar and Shikha Parmar, 1998).
Biological Effect # 5. Hepato-protective Activity:
Many flavonoids have also been found to possess hepato-protective activity. In a study carried out to investigate silymarin, apigenin, quercetin and naringenin as putative therapeutic agents against microcrystin LR-induced hepatotoxicity, silymarin was found to be the most effective one (Carlo et al., 1993). Rutin and venorutin showed regenerative and hepato-protective effects in experimental cirrhosis (Lorenz et al., 1973).
Biological Effect # 6. Antioxidant Activity:
Free radical production in animal cells can either be accidental or deliberate. With the increasing acceptance of free radicals as common place and important biochemical intermediates, they have been implicated in a large number of human diseases (Wegener & Fintelmann, 1999).
Quercetin, kaempferol, morin, myricetin and rutin by acting as antioxidants exhibited several beneficial effects, such as anti-inflammatory, anti-allergic, antiviral as well as an anticancer activity. They have also been suggested to play a protective role in liver diseases, cataracts, and cardiovascular diseases.
Quercetin and silybin acting as free radical scavengers were shown to exert a protective effect in reperfusion ischemic tissue damage (Santos et al., 1998).
The scavenging activity of flavonoids has been reported to be in the order: myricetin > quercetin > rhamnetins> morin diosmetin > naringenin > apigenin > catechin > 5, 7- dihydroxy-3′,4′,5′-trimethoxyflavone > robinin > kaempferol > flavone (Ratty, 1988). Morin, myricetin, kaempferol and quercetin have also been suggested as stabilizers for fish oil as an alternative to synthetic antioxidants (Husain et al., 1987).
Biological Effect # 7. Effect on Heat Shock Proteins:
Heat shock proteins (HSP) have been recognized against physiological stress such as heat shock, heavy metals and glucose starvation. Recent progress has revealed the role of HSPs in various diseases. HSP27 has been shown to be involved in the acquired resistance of tumor cells, hyper-thermic and chemotherapeutic treatment.
Aberrant expression of HSP could cause various autoimmune diseases. Flavonoids inhibited the expression of HSP27, HSP47, and HSP72/73 (Laughton et al., 1989). The results suggested the pharmacological possibilities of flavonoids in diseases derived from abnormal expression of JISPs.
Biological Effect # 8. Anti-Inflammatory Activity:
A number of flavonoids are reported to possess anti-inflammatory activity. Hesperidin, a citrus flavonoids possesses significant anti-inflammatory and analgesic effects (Shahidi et al., 1998).
Recently, apigenin, luteolin and quercetin have been reported to exhibit anti-inflammatory activity. Quercetin, gallic acid ethyl ester and some as yet unidentified flavonoids might account for the anti-nociceptive action reported for the hydro-alcoholic extract of Phyllanthus caroliniertsis.
Biological Effect # 9. Antineoplastic Activity:
Quite a number of flavonoids have exhibited antineoplastic activity. Study showed that the flavonoids quercetin, kaempferol, catechin, toxifolin and fisetin suppressed cell growth (Kim et al., 1993; Gill et al., 1994). On screening anti-leukemic efficacy of 28 naturally occurring and synthetic flavonoids on human promyelocytic leukaemic HL-60 cells, genistein, an iso-flavone was found to have strong effect.
Genistein is also reported to inhibit in a dose dependent manner the growth of HGC-27 cells derived from human gastric cancer. Of the 14 flavonoids tested against murine and human cancer cell lines, 2′, 6′-diacetoxy -4, 4′ –dimethoxydihydro chalcone was the most potent and showed selectivity for the cell line P-388 (Hirano et al., 1994). Trifolirhizin tetraacetate showed greater selectivity for the human cell lines.
Biological Effect # 10. Effects on Blood Vessels:
Quercetin and rutin have been used as effective constituents of several pharmaceuticals used for treatment of capillary fragility and phlebosclerosis. The activities of certain flavonoids in inhibiting capillary permeability and Arthus phenomenon were found to be in the following order, hesperitin > rutin > quercetin > naringenin > kaempferol > isoquercitol (Paul etal., 1997; Fritz et al., 1996).
Flavonoids tangeratin, hesperidin, quercetin, and rutin have been found to reduce aggregation of horse erythrocytes.
The decrease in blood cell aggregation produced by most of the flavonoids may explain the reported beneficial effects of these compounds on abnormal capillary permeability and fragility, the reduction of disease symptoms and their protection against various traumas and stresses (Versantvoort et al., 1993).
The flavonoids O- (beta-hydroxyethyl) rutoside, (+) – catechol, trihydroxyethyl rutoside increased the negative charge density of the blood vessel wall in vitro and were markedly anti-thrombo-genic (Griffith and Ballow, 1972). Quercetin also has been reported to inhibit aggregation of human platelets.
Other antiaggregatory flavonoids reported were 3-methyl quercetin, toxerutin, fisetin, dihydroquercetin and flavone. Nobeletin and sinense-tin decreased erythrocyte aggregation and sedimentation in vitro and might be useful in dietary control of high blood viscosity syndrome (Wenner et al., 1980). Orally administered flavonoids weakly inhibit the vascular permeability and prevent pulmonary haemorrhage.
Biological Effect # 11. Antimicrobial Activity:
a. Antibacterial Activity:
Most of the flavonoids studies were found to be active against many bacteria.
Most of the flavones having no sugar moiety showed antimicrobial activities whereas none of the flavonols and flavonolignans tested showed inhibitory activity on the microorganisms (Wild & Fasel, 1969). e.g. Quercetin, Baicalin, Quercetogetin, Hespertin, Fisetin, iso-liquiritigenin,Naringin, Rutin, Apigenin, Chrysin, Baicalin, Hydroxyethylrutosine, Datisetin, HydroxyethyIrutoside.
b. Antifungal Activity:
Number of flavonoids isolated from peel of tangerine orange, when tested for fungi static activity towards Deuterophoma tracheiphila showed promising activity. Chlorflavonin was the first chlorine-containing flavonoid type antifungal antibiotic produced by strains of Aspergillus carididus (Tencate et al., 1973). e.g. Chloroflavonin, Quercetin, Chrysoeriol, Rutin, Epicathenin, Apigenin, Echinacin, Phaseolinisoflavan.
c. Antiviral Activity:
Flavonoids also displayed antiviral, including anti-HIV activity. It has been found that flavonols are more active than flavones against herpes simplex virus type 1 and the order of importance was galangin > kaempferol > quercetin (Thomas et al., 1988). e.g. Quercetrin, Rutin, Galangin, Kemp- ferol, Apigenin, Chrysin, Morin, Naringin, Luteolin.
