Phytoestrogens: recent developments

Abstract

Phytoestrogens are polyphenolic non-steroidal plant compounds with estrogen like activity exerted through estrogen receptors. These receptors are distributed in several tissues such as male and female reproductive systems, bones, cardiovascular and central nervous systems. These natural phenolic compounds include isoflavonoids, flavonoids, lignans and stilbenes. Isoflavonoids are the most studied group of phytoestrogens, which can be found in the family leguminosae such as soybeans, alfalfa and clover. Daidzine and genistein are the principal isoflavonoids, which are found in plants as glycoside derivatives. These compounds can be metabolized in the digestive tract by normal microflora to their corresponding aglycones. The aglycones are absorbed through non-ionic passive diffusion. After absorption, they are readily conjugated with glucuronic acid and excreted in urine. Isoflavonoids have a good binding affinity for estrogen receptors (ER? and ER?) but they activate the intracellular mechanism (such as transcription and protein synthesis) less than steroidal estrogen. The estrogen receptor relative binding affinities of isoflavonoids when tested decreased in the following order: 17?-estradiol >coumestrol > genistein > equal >daidzien Nowadays, the relation between various diseases and estrogens are clearly identified. At menopause, the secretion of estrogens is reduced and as a result, osteoporosis, cardiovascular diseases (CVD) and menopausal symptoms occur. For the treatment of such conditions, estrogen is used but estrogen therapy may increase the risk of breast cancer. Isoflavonoids can be bonded to estrogen receptors and regulate LDL-receptor activity and can also suppress the osteoclasts in the bone tissue and reduce the risk of osteoporosis. Therefore, these compounds can be recommended to prevent the menopausal symptoms. Isoflavonoids can also be used in estrogen related cancers. These compounds may inhibit the 5?-reductase enzymes, decrease production of androgens, and so reduce the risk of prostate cancer. Furthermore, they can activate the estrogen receptors less than estrogenic compounds. Therefore, they can be used in estrogen-dependent breast cancers. In addition to enzyme inhibition activities, isoflavonoids at very high concentrations have anti-angiogenesis and antioxidant effects. The most important adverse effect of isoflavonoid is infertility syndrome in animals. The suppression of immune system is also reported. The aim of the article is to review the chemical structures, biological effects, therapeutic uses and adverse effects of phytoestrogens.