Abstract：
: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.
journal_name
Neurochem Intjournal_title
Neurochemistry internationalauthors
Wang CC,Ho YH,Hung CF,Kuo JR,Wang SJdoi
10.1016/j.neuint.2019.104629subject
Has Abstractpub_date
2020-02-01 00:00:00pages
104629eissn
0197-0186issn
1872-9754pii
S0197-0186(19)30496-6journal_volume
133pub_type
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