Stigmasterol exerts neuro-protective effect against ischemic/reperfusion injury through reduction of oxidative stress and inactivation of autophagy

Abstract

Purpose: Stroke remains the primary cause of pain, suffering, and death in patients. One of the major thrusts in stroke therapy is to find an effective prevention strategy. Objectives of this study are to testify the neuro-protection effect of stigmasterol in ischemic/reperfusion injury model. Methods: The dosage-dependent effects (20, 40, and 80 mg/kg) of stigmasterol on physiological behaviors and oxidative stress biomarkers were investigated. Expression and phosphorylation of beclin1, microtubule-associated protein 1 light chain 3 (LC3), adenosine monophosphate-activated protein kinase (AMPK), mTOR, and N-terminal kinase (JNK) were detected. Results: The results showed that stigmasterol was able to effectively reduce neurological deficits and infarct damage induced by the ischemic/reperfusion injury, improve histopathol-ogy changes, and restore the levels of the endogenous antioxidant defense system in a dose– response mode. Stigmasterol effectively depressed the expression level of beclin1, and the conversion of LC3 I to LC3 II, while promoted the phosphorylation of mTOR, and remarkably inhibited the phosphorylation of AMPK and JNK, as well as the expression of JNK induced by 24 hrs of reperfusion. Conclusion: These findings reveal that stigmasterol has neuro-protective effect against the ischemic/reperfusion injury, possibly associated with reduction of oxidative stress and inactivation of autophagy via AMPK/mTOR and JNK pathways.