• Zhen Song, Shuai Han, Xiaohua Pan, Yaoqin Gong, and Molin Wang.
• Department of Genetics, Key Laboratory for Experimental Teratology of the Ministry of Education, Shandong University, Jinan, Shandong, China.
• J. Pharm. Pharmacol. 2015 May 1; 67 (5): 720-30.

ObjectivesAccumulating evidence indicated protective role of phytoestrogens against neuronal damage induced by various insults, such as amyloid beta, oxygen deprivation and mitochondrial toxins. Hydrogen peroxide (H2 O2 ) influences the mitochondrial membrane potential, which eventually results in cell apoptosis. In this study, we investigated the effects and possible mechanisms of a phytoestrogen, pterostilbene (PTER), in cell apoptosis induced by H2 O2 in human neuronal SH-SY5Y cells. We also analysed the involvement of oestrogen receptors, oestrogen receptor-α and -β (ER-α and ER-β) in the protective role of PTER.MethodsThe effects of PTER on H2 O2 -stimulated cell were examined using MTT and FACS analysis. The signal pathways and estrogen receptors involved in PTER's effects were investigated using MTT and Western blot analysis.Key FindingsThe results showed that H2 O2 treatment significantly reduced cell viability in SY5Y cells, which was protected by PTER treatment. We also found that H2O2 inhibited the PI3K/AKT and MAPK/ERK signalling pathways, whereas PTER treatment restored these signalling pathways. We also found that the PTER effect could be largely blocked by an ER-α antagonist, 3-Bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]-1H-pyrazole dihydrochloride (MPP), but not by an ER-β antagonist, 4-[2-Phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-a] pyrimidin-3-yl]phenol (PHTPP), suggesting that ER-α is a major player in the neuroprotective activity of PTER.ConclusionOur study thus demonstrates that PTER is an effective neuroprotective agent presumably through ER-α-mediated signalling pathways.© 2015 Royal Pharmaceutical Society.

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