Anemoside B۴ mitigates endoplasmic reticulum stress-induced apoptosis post cerebral ischemia/reperfusion injury in rats

Objective(s): Anemoside B۴ (AB۴) exhibits neuroprotective effects on cerebral ischemia/reperfusion injury (CIRI), and endoplasmic reticulum stress (ERS) plays a crucial role in the process of CIRI. Nevertheless, it remains unknown whether AB۴ acts on CIRI via ERS. This study is designed to determine whether AB۴ mitigates CIRI by suppressing ERS-induced neuronal apoptosis.Materials and Methods: One hundred thirty-five male SD rats (۲۶۰–۲۹۰ g) were randomly assigned to five groups, with ۲۰ rats in each group: ① Sham. ② Middle Cerebral Artery Occlusion (MCAO/R). ③AB۴-L: Prior to MCAO, rats were subjected to continuous intraperitoneal injection of ۱.۲۵ mg/kg of AB۴.④AB۴-M: Rats were administered a continuous intraperitoneal injection of ۲.۵ mg/kg of AB۴ prior to undergoing MCAO.⑤AB۴-H: Rats were continuously intraperitoneally injected with ۵ mg/kg of AB۴ before MCAO. Additionally, another thirty-five rats were employed for the time point. Results: TTC staining results demonstrated that AB۴ significantly reduced cerebral infarct volume. Histopathological analysis of brain tissues revealed that AB۴ mitigated neuronal damage. In the MCAO model, GRP۷۸ expression progressively increased with reperfusion time and peaked at ۲۴ hr. AB۴ treatment decreased mRNA levels of key ERS markers, including GRP۷۸, ATF۶, IRE۱α, and PERK. Additionally, AB۴ reduced protein levels of GRP۷۸, p-PERK, PERK, ATF۶, and p-IRE۱α, further indicating its role in attenuating ERS. TUNEL results demonstrated that AB۴ significantly reduced neuronal apoptosis.Conclusion: AB۴ may serve as a potential therapeutic agent for CIRI, potentially exerting neuroprotective effects through inhibiting ERS-mediated apoptosis.

کلیدواژه ها:

Anemoside B۴ ، Apoptosis ، Cerebral ischemia/ - reperfusion injury ، Endoplasmic reticulum - stress ، MCAO/R