Echinocystic acid (EA) was found to possess antiviral, anti-inflammatory and antioxidation activities. A recent study showed the antiapoptotic effects of EA on acute myocardial infarction. In this study, we demonstrated the potential neuroprotective effects of EA on cerebral ischemia/reperfusion (I/R) injury in mice. Intraperitoneal injection of EA 1 h before ischemia significantly reduced the cerebral infarct volume and neurological deficit after 60 min of ischemia and 24 h of reperfusion. The neuroprotective effects of EA occurred in a dose-dependent manner. Then, we explored the mechanisms of neuroprotection by EA. This compound exerted antiapoptotic activity by upregulating the level of Bcl-2 and simultaneously downregulating the levels of cleaved caspase-3 and Bax. Furthermore, EA also possessed anti-inflammatory activity and prevented the excessive phosphorylation of NF-κB (p-P65) and the increase in IL-1β and IL-6 levels. Finally, our data indicated that EA treatment decreased the level of phosphorylated JNK in vivo, and the JNK activator anisomycin (AN) reversed the neuroprotective effects of EA, indicating that the JNK pathway is involved in the antiapoptotic and anti-inflammatory mechanisms of EA. In summary, our findings suggest that EA provides neuroprotective effects through its antiapoptotic and anti-inflammatory activities by inhibiting the JNK signaling pathway in cerebral I/R injury. Due to its safety and lack of toxicity, EA is a potential candidate for the treatment of ischemic stroke in future clinical trials.
Keywords: Apoptosis; Cerebral ischemia/reperfusion; Echinocystic acid; Inflammation; JNK signal pathway.
Copyright © 2019 Elsevier B.V. All rights reserved.