Previous study has shown that icaritin (ICT) has meaningful protective effect on cerebral ischemic stroke, and this study aimed to investigate its mechanism from the aspect of protecting astrocytes from oxidative stress. Murine primary astrocytes were pretreated by ICT and exposed to H2 O2 to induce oxidative stress. The results indicated that ICT inhibited H2 O2 -induced astrocytes apoptosis, decreased Bax and cleaved caspase-3, and increased Bcl-2. In addition, ICT inhibited H2 O2 -induced oxidative stress, increased mitochondrial membrane potential (ΔΨm ), and maintained mitochondrial morphology. ICT decreased the synthesis of malondialdehyde and increased the activity of glutathione peroxidase, catalase, and superoxide dismutase. Moreover, ICT suppressed the transient and resting intracellular Ca2+ overload. Further investigation revealed that ICT could target the combination with Orai1 to block store-operated calcium channel induced by H2 O2 . However, ICT did not enhance the protective effect of RO2959, a selective blocker of Orai1. These results indicate that ICT can play a neuroprotective role against oxidative stress injury by binding to Orai1 to block SOCC.
Keywords: Icaritin; Orai1; astrocyte; oxidative stress; store-operated calcium channel.
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