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  • Title: Protection by genistein on cortical neurons against oxidative stress injury via inhibition of NF-kappaB, JNK and ERK signaling pathway.
    Author: Qian Y, Cao L, Guan T, Chen L, Xin H, Li Y, Zheng R, Yu D.
    Journal: Pharm Biol; 2015 Aug; 53(8):1124-32. PubMed ID: 25715966.
    Abstract:
    CONTEXT: Genistein, one of the isoflavones derived from soybean seeds, has been reported to exert multiple bioactivities. However, the mechanism of its action on the central nervous system is not fully understood. OBJECTIVE: To investigate the cytoprotection of genistein and its molecular mechanism against H2O2-induced cell death in primary rat cortical neurons. MATERIALS AND METHODS: Genistein (0.01, 0.1, and 1 μM) were added into the primary rat neurons 24 h before and co-cultured with 500 μM H2O2 for 1 h. Neuronal injury was assessed by MTT, lactate dehydrogenase (LDH) assay, and Hoechst33258 staining. Intracellular reactive oxygen species (ROS) generation induced by H2O2 was determined. Neuronal apoptosis was evaluated by Bcl-2/Bax ratio as well as by caspase-9 and caspase-3 activities. The protein levels and phosphorylation of NF-κB/p65, IκB, JNK, and ERK were detected by western blots. RESULTS: Genistein pretreatment attenuated H2O2-mediated neuronal viability loss, nuclear condensation, and ROS generation in a concentration-dependent manner. Genistein exerted anti-apoptotic effects by reversing the apoptotic factors Bcl-2 and Bax ratio, along with the suppression of caspase-9 and caspase-3 activities. In addition, genistein down-regulated the expression of NF-κB/p65, and suppressed the phosphorylation of p65 and IκB. Genistein also inhibited H2O2-induced activation of the MAPK-signaling pathway including JNK and ERK. DISCUSSION AND CONCLUSION: The results indicated that genistein effectively protects cortical neurons against oxidative stress at least partly via inactivation of NF-κB as well as MAPK-signaling pathways, and suggested the possibility of this antioxidant for the prevention and treatment of stroke.
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