Flavonoids are nearly ubiquitous in plants and are recognized as the pigments responsible for the colors of leaves, especially in autumn. They are rich in seeds, citrus fruits, olive oil, tea, and red wine. They are low molecular weight compounds composed of a three-ring structure with various substitutions. This basic structure is shared by tocopherols (vitamin E). Flavonoids can be subdivided according to the presence of an oxy group at position 4, a double bond between carbon atoms 2 and 3, or a hydroxyl group in position 3 of the C (middle) ring. These characteristics appear to also be required for best activity, especially antioxidant and antiproliferative, in the systems studied. The particular hydroxylation pattern of the B ring of the flavonoles increases their activities, especially in inhibition of mast cell secretion. Certain plants and spices containing flavonoids have been used for thousands of years in traditional Eastern medicine. In spite of the voluminous literature available, however, Western medicine has not yet used flavonoids therapeutically, even though their safety record is exceptional. Suggestions are made where such possibilities may be worth pursuing.

The Effects of Plant Flavonoids on Mammalian Cells:Implications for Inflammation, Heart Disease, and Cancer

The biochemistry and medical significance of the flavonoids.

Flavonoids : old and new aspects of a class of natural therapeutic drugs

Antioxidants are substances that may protect cells from the damage caused by unstable molecules such as free radicals. Flavonoids are phenolic substances widely found in fruits and vegetables. The previous studies showed that the ingestion of flavonoids reduces the risk of cardiovascular diseases, metabolic disorders, and certain types of cancer. These effects are due to the physiological activity of flavonoids in the reduction of oxidative stress, inhibiting low-density lipoproteins oxidation and platelet aggregation, and acting as vasodilators in blood vessels. Free radicals are constantly generated resulting in extensive damage to tissues leading to various disease conditions such as cancer, Alzheimer's, renal diseases, cardiac abnormalities, etc., Medicinal plants with antioxidant properties play a vital functions in exhibiting beneficial effects and employed as an alternative source of medicine to mitigate the disease associated with oxidative stress. Flavonoids have existed over one billion years and possess wide spectrum of biological activities that might be able to influence processes which are dysregulated in a disease. Quercetin, a plant pigment is a potent antioxidant flavonoid and more specifically a flavonol, found mostly in onions, grapes, berries, cherries, broccoli, and citrus fruits. It is a versatile antioxidant known to possess protective abilities against tissue injury induced by various drug toxicities.

Overviews of Biological Importance of Quercetin: A Bioactive Flavonoid.

Phytogenic agents have traditionally been used by herbalists and indigenous healers for the prevention and treatment of peptic ulcer. This article reviews the anti-acid/anti-peptic, gastro-protective and/or anti-ulcer properties of the most commonly employed herbal medicines and their identified active constituents. Botanical compounds with anti-ulcer activity include flavonoids (i.e. quercetin, naringin, silymarin, anthocyanosides, sophoradin derivatives) saponins (i.e. from Panax japonicus and Kochia scoparia), tannins (i.e. from Linderae umbellatae), gums and mucilages (i.e. gum guar and myrrh). Among herbal drugs, liquorice, aloe gel and capsicum (chilli) have been used extensively and their clinical efficacy documented. Also, ethnomedical systems employ several plant extracts for the treatment of peptic ulcer. Despite progress in conventional chemistry and pharmacology in producing effective drugs, the plant kingdom might provide a useful source of new anti-ulcer compounds for development as pharmaceutical entities or, alternatively, as simple dietary adjuncts to existing therapies.

The plant kingdom as a source of anti‐ulcer remedies

This study was designed to determine the cytoprotective properties of quercetin and the involvement of endogenous prostaglandins in mucosal injury produced by absolute ethanol. Gastric glands were also analyzed histologically. Oral pretreatment with the highest dose of quercetin (200 mg/kg), 120 min before absolute ethanol, was most effective in necrosis prevention. Subcutaneous administration of indomethacin (10 mg/kg) to the animals treated with quercetin (200 mg/kg) partially inhibited gastric protection. All treated groups showed a marked increase in the amount of gastric mucus although this increase was less in animals pretreated with indomethacin. Total proteins and the hexosamine content decreased in the groups receiving indomethacin. The histomorphometric evaluation of the gastric damage confirmed a significant increase in mucus production accompanied by a parallel reduction of gastric lesions with the highest dose of quercetin tested.

Antiulcer and gastroprotective effects of quercetin: a gross and histologic study.

The antiulcerogenic effect of two flavonoids, quercetin and naringenin, in acute gastric ulcer (cold-restraint and pylorus-ligated) has been investigated. In both models quercetin and naringenin presented a significant decrease in ulcer index with respect to the control group. Nevertheless, in the Shay-ligated method no decrease in either volume, acidity or pepsin were observed, however, a significant difference was found in histamine secretion values.

Quercetin and naringenin; effects on ulcer formation and gastric secretion in rats

— This study was designed to determine the cytoprotective properties of naringenin and the involvement of endogenous prostaglandins on mucosal injury produced by absolute ethanol Gastric glands were also histologically analysed Oral pretreatment with the highest dose of naringenin (200 mg kg−1), 240 min before absolute ethanol, was the most effective in ulcer prevention Subcutaneous administration of indomethacin (10 mg kg−1) to the animals treated with naringenin (200 mg kg−1) partially inhibited the gastric protection but there was no increase in prostaglandin E2 All treated groups showed a marked increase in gastric mucus, although this increase was less in animals pretreated with indomethacin Total proteins and hexosamine content decreased in the groups receiving indomethacin Histomorphometric evaluation of the gastric damage, with the highest dose of naringenin (200 mg kg−1), confirmed a significant increase of mucus production accompanied by a parallel reduction of gastric lesion

Ulcer-protecting effects of naringenin on gastric lesions induced by ethanol in rat: role of endogenous prostaglandins.

— Oral treatment with silymarin was found to be effective in the prevention of gastric ulceration induced by cold-restraint stress, in rats. Statistically significant ulcer index values with respect to the control group, were observed. In 6 h pyloric-ligated animals silymarin showed a significant reduction in the number and severity of the ulcers; however, it did not alter the gastric secretion volume or acidity although histamine concentration was significantly decreased. In absolute ethanol-induced ulcers, treatment with silymarin 1 or 2 h before the anti-ulcerogenic agent, did not prevent the formation of gastric lesions. Furthermore, the hexosamine content was decreased significantly, but the total protein output was enhanced, showing similar values to those with the standard drug, carbenoxolone. These results suggest that the anti-ulcerogenic effect of silymarin could be related to its inhibitory mechanism of enzymatic peroxidation by the lipoxygenase pathway, avoiding leukotriene synthesis.

M. J. Martin

Papers

Antiulcer and gastroprotective effects of quercetin: a gross and histologic study.

Quercetin and naringenin; effects on ulcer formation and gastric secretion in rats

Ulcer-protecting effects of naringenin on gastric lesions induced by ethanol in rat: role of endogenous prostaglandins.

Gastric anti-ulcer activity of silymarin, a lipoxygenase inhibitor, in rats.

Antiulcerogenicity of the flavonoid fraction from Bidens aurea: comparison with ranitidine and omeprazole.