Inhibitory Effect of Isoflavones on Peroxynitrite-mediated Low-density Lipoprotein Oxidation

Abstract

Peroxynitrite, a potent oxidant formed in vivo from the reaction of nitric oxide with superoxide, can mediate low-density liprotein (LDL) oxidation which is thought to increase the risk of atherosclerosis. This study investigates the inhibitory effect of the isoflavones, genistein and daidzein, together with their glycosidic forms, genistin and daidzin, on the peroxynitrite-mediated LDL oxidation and nitration of tyrosine. Genistein and daidzein were observed to dose-dependently inhibit peroxynitrite-mediated LDL oxidation, while their glucoside conjugates showed less activity. Moreover, all the isoflavones used in this study were found to be potent peroxynitrite scavengers, preventing the nitration of tyrosine. The ability of the isoflavones at 50 microM to decrease the tyrosine nitration induced by peroxynitrite (1 mM) was in the ratios of genistein (49%), daidzein (40%), daidzin (41%) and genistin (42%) when compared to the control (tyrosine incubated only with peroxynitrite). These results suggest that an intake of isoflavones could contribute to protecting against cardiovascular diseases and chronic inflammatory diseases.

Flavonoids as anti-inflammatory agents: implications in cancer and cardiovascular disease

“…Selected flavonoids can directly scavenge superoxides [34], whereas other flavonoids such as genistein and daidzein can scavenge the highly reactive oxygen-derived radical peroxynitrite [35]. Epicatechin and rutin have a powerful hydroxyl radical (OHÁ) scavenging effect, about 100-300 times higher than mannitol, a typical OHÁ scavenger, and also inhibit the superoxide anion (O 2 -) generation in the hypoxanthine-xanthine oxidase system [36].…”

“…Also, nitric oxide can be viewed as a radical itself, and it has been reported that nitric oxide molecules are directly scavenged by flavonoids [39]. The soybean isoflavones genistein and daidzein increase LDL resistance to peroxynitrite-mediated oxidation, in vitro, in a concentration-dependent fashion [35]. In vivo experiments have demonstrated that oral administration of isoflavones and extracts from soy-based products decrease serum nitrite, nitrate and nitrotyrosine levels in LPS-induced rats [40].…”

Bioactive Chromone Derivatives – Structural Diversity

“…In fact, this was found to be mainly governed by the number, pK a values and arrangement of the hydroxyl groups in the chromone ring system, as expected, since these are the groups responsible for the molecule´s reductive capacity through the formation of a stable radical [51,52,147,148]. Hence, a good correlation has been obtained between antioxidant and radical scavenging capacities and the hydroxyl bond strength, electron-donating ability (ionisation potential estimated by the HOMO energy), enthalpy of single electron transfer and spin distribution of the phenoxyl radicals after H-abstraction [52,138].…”

Isoflavone Content and Anti-acetylcholinesterase Activity in Commercial Douchi (a Traditional Chinese Salt-fermented Soybean Food)

“…Soybean isoflavones have been widely studied because of their physiological properties. They are known as phytoestrogens and have been shown to be effective in preventing osteoporosis 8 , lowering breast cancer risk 12 , inhibiting oxidative damage 11 , and alleviating menopausal symptoms 8 . The effects depend on the structures of isoflavones in various bioactivities.…”