Affiliation:
1. School of Pharmacy Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University Yantai China
2. Department of Pharmacy Binzhou Medical University Hospital Binzhou China
3. Department of Radiology Binzhou Medical University Hospital Binzhou China
4. College of Basic Medicine Binzhou Medical University Yantai China
Abstract
AbstractHigh‐mobility group box1 (HMGB1) induces inflammatory injury, and emerging reports suggest that it is critical for brain ischemia reperfusion. Engeletin, a natural Smilax glabra rhizomilax derivative, is reported to possess anti‐inflammatory activity. Herein, we examined the mechanism of engeletin‐mediated neuroprotection in rats having transient middle cerebral artery occlusion (tMCAO) against cerebral ischemia reperfusion injury. Male SD rats were induced using a 1.5 h tMCAO, following by reperfusion for 22.5 h. Engeletin (15, 30 or 60 mg/kg) was intravenously administered immediately following 0.5 h of ischemia. Based on our results, engeletin, in a dose‐dependent fashion, reduced neurological deficits, infarct size, histopathological alterations, brain edema and inflammatory factors, namely, circulating IL‐1β, TNF‐α, IL‐6 and IFN‐γ. Furthermore, engeletin treatment markedly reduced neuronal apoptosis, which, in turn, elevated Bcl‐2 protein levels, while suppressing Bax and Cleaved Caspase‐3 protein levels. Meanwhile, engeletin significantly reduces overall expressions of HMGB1, TLR4, and NF‐κB and attenuated nuclear transfer of nuclear factor kappa B (NF‐κB) p65 in ischemic cortical tissue. In conclusion, engeletin strongly prevents focal cerebral ischemia via suppression of the HMGB1/TLR4/NF‐κB inflammatory network.
Funder
National Natural Science Foundation of China
Project of Shandong Province Higher Educational Science and Technology Program
Subject
Cell Biology,Molecular Medicine
Cited by
15 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献