Schisantherin A attenuates ischemia/reperfusion-induced neuronal injury in rats via regulation of TLR4 and C5aR1 signaling pathways

被引:30
作者
Shi, Yun Wei [1 ,2 ,3 ]
Zhang, Xiao Chuan [1 ,2 ,3 ]
Chen, Chen [1 ,2 ,3 ]
Tang, Miao [1 ,2 ,3 ]
Wang, Zhi Wei [1 ,2 ,3 ,4 ]
Liang, Xin Miao [1 ,2 ,3 ,5 ]
Ding, Fei [1 ,2 ,3 ]
Wang, Cai Ping [1 ,2 ,3 ]
机构
[1] Nantong Univ, Key Lab Neuroregenerat Jiangsu, 19 Qixiu Rd, Nantong 226001, Jiangsu, Peoples R China
[2] Nantong Univ, Minist Educ, 19 Qixiu Rd, Nantong 226001, Jiangsu, Peoples R China
[3] Nantong Univ, Coinnovat Ctr Neuroregenerat, Nantong 226001, Jiangsu, Peoples R China
[4] Univ Calif Irvine, Dept Pharmacol, Irvine, CA 92697 USA
[5] Chinese Acad Sci, Dalian Inst Chem Phys, Dalian 116023, Liaoning, Peoples R China
基金
中国国家自然科学基金;
关键词
C5aR1; TLR4; Schisantherin A; Inflammation; Apoptosis; Neuroprotection; FOCAL CEREBRAL-ISCHEMIA; NF-KAPPA-B; DIBENZOCYCLOOCTADIENE LIGNANS; FUNCTIONAL RECOVERY; BRAIN-INJURY; PROTECTS; COMPLEMENT; RECEPTOR; INHIBITION; DAMAGE;
D O I
10.1016/j.bbi.2017.07.004
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
Toll-like receptor 4 (TLR4) and C5aR1 (CD88) have been recognized as potential therapeutic targets for the reduction of inflammation and secondary damage and improvement of outcome after ischemia and reperfusion (I/R). The inflammatory responses which induce cell apoptosis and necrosis after I/R brain injury lead to a limited process of neural repair. To further comprehend how these targets function in I/R state, we investigated the pathological changes and TLR4 and C5aR1 signaling pathways in vitro and in vivo models of I/12 brain injury in this study. Meanwhile, we explored the roles of schisantherin A on I/R brain injury, and whether it exerted neuroprotective effects by regulating the TLR4 and C5aR1 signaling pathways or not. The results showed that schisantherin A significantly reduced the neuronal apoptosis induced by oxygen and glucose deprivation and reperfusion (OGD/R) injury in primary culture of rat cortical neurons. Also, schisantherin A alleviated neurological deficits, reduced infarct volume, attenuated oxidation stress, inflammation and apoptosis in ischemic parietal cortex of rats after middle cerebral artery occlusion and reperfusion (MCAO/R) injury. Moreover, the activated TLR4 and C5aR1 signaling pathways were inhibited by schisantherin A treatment. In conclusion, TLR4 and C5aR1 played a vital role during I/R. brain injury in rats, and schisantherin A exhibited neuroprotective effects by TLR4 and C5aR1 signaling pathways. These findings also provided new insights that would aid in elucidating the effect of schisantherin A against cerebral I/12 and support the development of schisantherin A as a potential treatment for ischemic stroke. (C) 2017 Elsevier Inc. All rights reserved.
引用
收藏
页码:244 / 256
页数:13
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