Genistein

Genistein is an isoflavone that is described as an angiogenesis inhibitor and a phytoestrogen. It was first isolated in 1899 from the dyer's broom, Genista tinctoria; hence, the chemical name. The compound structure was established in 1926, when it was found to be identical with that of prunetol. It was chemically synthesized in 1928. Genistein is an isoflavone that is described as an angiogenesis inhibitor and a phytoestrogen. It was first isolated in 1899 from the dyer's broom, Genista tinctoria; hence, the chemical name. The compound structure was established in 1926, when it was found to be identical with that of prunetol. It was chemically synthesized in 1928. Isoflavones such as genistein and daidzein are found in a number of plants including lupin, fava beans, soybeans, kudzu, and psoralea being the primary food source, also in the medicinal plants, Flemingia vestita and F. macrophylla, and coffee. It can also be found in Maackia amurensis cell cultures. Most of the isoflavones in plants are present in a glycosylated form. The unglycosylated aglycones can be obtained through various means such as treatment with the enzyme β-glucosidase, acid treatment of soybeans followed by solvent extraction, or by chemical synthesis. Acid treatment is a harsh method as concentrated inorganic acids are used. Both enzyme treatment and chemical synthesis are costly. A more economical process consisting of fermentation for in situ production of β-glucosidase to isolate genistein has been recently investigated. Besides functioning as antioxidant and anthelmintic, many isoflavones have been shown to interact with animal and human estrogen receptors, causing effects in the body similar to those caused by the hormone estrogen. Isoflavones also produce non-hormonal effects. Genistein influences multiple biochemical functions in living cells: Isoflavones genistein and daidzein bind to and transactivate all three PPAR isoforms, α, δ, and γ. For example, membrane-bound PPARγ-binding assay showed that genistein can directly interact with the PPARγ ligand binding domain and has a measurable Ki of 5.7 mM. Gene reporter assays showed that genistein at concentrations between 1 and 100 uM activated PPARs in a dose dependent way in KS483 mesenchymal progenitor cells, breast cancer MCF-7 cells, T47D cells and MDA-MD-231 cells, murine macrophage-like RAW 264.7 cells, endothelial cells and in Hela cells. Several studies have shown that both ERs and PPARs influenced each other and therefore induce differential effects in a dose-dependent way. The final biological effects of genistein are determined by the balance among these pleiotrophic actions. The main known activity of genistein is tyrosine kinase inhibitor, mostly of epidermal growth factor receptor (EGFR). Tyrosine kinases are less widespread than their ser/thr counterparts but implicated in almost all cell growth and proliferation signal cascades. Genistein may act as direct antioxidant, similar to many other isoflavones, and thus may alleviate damaging effects of free radicals in tissues. The same molecule of genistein, similar to many other isoflavones, by generation of free radicals poison topoisomerase II, an enzyme important for maintaining DNA stability.