Genistein, the Dietary-Derived Angiogenesis Inhibitor, Prevents LDL Oxidation and Protects Endothelial Cells From Damage by Atherogenic LDL

Abstract

There is now growing evidence that the oxidative modification of LDL plays a potential role in atherosclerosis. In this study, genistein, a compound derived from a soy diet with a flavonoid chemical structure (4',5,7-trihydroxyisoflavone), which was found to inhibit angiogenesis, has been evaluated for its ability to act as an LDL antioxidant and a vascular cell protective agent against oxidized LDL. The results showed that genistein was able to inhibit the oxidation of LDL in the presence of copper ions or superoxide/nitric oxide radicals as measured by thiobarbituric acid-reactive substance formation, alteration in electrophoretic mobility, and lipid hydroperoxides. Bovine aortic endothelial cell- and human endothelial cell-mediated LDL oxidation was also inhibited in the presence of genistein. The 7-O-glucoside of genistein, genistin, was much less effective in inhibiting LDL oxidation in the cell-free and cell-mediated lipoprotein-oxidating systems. Incubating human endothelial cells in the absence or presence of genistein and challenging the cells with already oxidized lipoprotein revealed that in addition to its antioxidative potential during LDL oxidating processes, genistein effectively protected the vascular cells from damage by oxidized lipoproteins. The tyrosine kinase inhibitor genistein was found to block upregulation of two tyrosine-phosphorylated proteins of 132 and 69 kDa in endothelial cells induced by oxidized LDL. Parallel experiments with the inactive analogue daidzein, however, showed that the cytoprotective effect of the isoflavones seems not to be dependent on tyrosine phosphorylation. Our findings will support the suggested and documented beneficial action of a soy diet in preventing chronic vascular diseases and early atherogenic events.

The Protective Effect of the Soybean Polyphenol Genistein against Stress-Induced Gastric Mucosal Lesions in Rats, and Its Hormonal Mechanisms

“…Moreover, the present study demonstrated that genistein treatment resulted in a decrease in gastric mucosal TBARS, which is considered a good indicator of lipid peroxidation, in the WIR stress model. Since genistein contains a phenol hydroxyl residue and has a potent radical scavenging effect (2,28,29), data from the present experiments indicate that genistein may act as an antioxidant in the gastric mucosa, thereby scavenging ROS in the gastric mucosa.…”

“…Isoflavones contains three aglycones: genistein, daidzein, and glycitein. In particular, genistein exerts various effects, including estrogen-like activity ( 1 ), anti-oxidant effects ( 2 ), and an anti-cancer effect ( 3 ). In the gastrointestinal field, genistein has been reported to inhibit activity of Helicobacter pylori , a bacterium that plays a pathophysiologic role in gastritis and gastric ulcer formation ( 4 ).…”

Animal Models Impacted by Phytoestrogens in Commercial Chow: Implications for Pathways Influenced by Hormones

“…These compounds also inhibit the activity of a number of enzymes (Adlercreutz et al, 1993a;Evans et al, 1995;Makela et al, 1995a). Isoflavones have antioxidant activity (Wei et al, 1995), which in vivo has been shown to reduce the susceptibility of lipids to oxidation (Jenkins et al, 2000;Kapiotis et al, 1997;Ruiz-Larrea et al, 1997;Sheiber et al, 1999;Tikkanen et al, 1998) contributing to the overall cardio-protective effects of soy protein by favorably influencing lipid homeostasis (Anderson et al, 1995;Crouse et al, 1999).…”

Fitoestrogênios: posicionamento do Departamento de Endocrinologia Feminina da Sociedade Brasileira de Endocrinologia e Metabologia (SBEM)

“…O LDL-colesterol retirado de indivíduos que usam proteína de soja, parece ser também mais resistente à oxidação in vitro (56,57) . Foi observada ação antioxidante da quercetina in vitro , o que poderia proteger contra o dano oxidativo ao LDL implicado na aterogênese.…”