Xanthohumol, an active constituent from hope, affords protection against kainic acid-induced excitotoxicity in rats.
Ključne riječi
Sažetak
Excitotoxicity induced by excessive glutamate has been implicated in many brain disorders. Xanthohumol is a natural product derived from hops (Humulus lupulus L.), which is reported to have glutamate release-inhibiting activity. However, it is unknown whether xanthohumol has protective effects against glutamate-induced excitotoxicity. This study investigated the potential action of xanthohumol in a rat model of excitotoxicity induced by intraperitoneal injection of kainic acid (KA). Xanthohumol (10 or 50 mg/kg) administrated intraperitoneally 30 min prior to KA (15 mg/kg) considerably ameliorated KA-induced seizures, glutamate concentration elevation, and CA3 neuron death. The decrease of mitochondrial fusion protein Mfn-2 and antiapoptotic protein Bcl-2 expression in hippocampal tissues following KA injection were reversed by xanthohumol. Moreover, apoptotic protease activating factor 1 (Apaf-1) expression and caspase-3 activation in the hippocampus were inhibited by xanthohumol. These results suggest that xanthohumol up-regulates Mfn-2 and Bcl-2 to preserve mitochondrial function and suppress Apaf-1 and caspase-3 activation, thereby increasing neuron survival in rats after KA treatment. Therefore, xanthohumol has great potential for development into a therapeutic agent for improving glutamate-related nervous system diseases.