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

• Published in: Brain, behavior, and immunity behavior, and immunity, 2017-11, Vol.66, p.244-256
• Main Authors: Shi, Yun Wei, Zhang, Xiao Chuan, Chen, Chen, Tang, Miao, Wang, Zhi Wei, Liang, Xin Miao, Ding, Fei, Wang, Cai Ping
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Brain Ischemia - complications; Brain Ischemia - metabolism; Brain Ischemia - prevention & control; C5aR1; Cell Survival - drug effects; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Cerebral Cortex - pathology; Cyclooctanes - administration & dosage; Dioxoles - administration & dosage; Inflammation; Inflammation - etiology; Inflammation - metabolism; Lignans - administration & dosage; Necrosis - drug therapy; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Neuroprotection; Neuroprotective Agents - administration & dosage; Oxidative Stress; Parietal Lobe - drug effects; Parietal Lobe - metabolism; Parietal Lobe - pathology; Primary Cell Culture; Rats, Sprague-Dawley; Receptor, Anaphylatoxin C5a - metabolism; Reperfusion Injury - complications; Reperfusion Injury - metabolism; Reperfusion Injury - prevention & control; Schisantherin A; Signal Transduction; TLR4; Toll-Like Receptor 4 - metabolism
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/j.bbi.2017.07.004

•I/R induces oxidative stress, inflammation and apoptosis in parietal cortex of rats.•TLR4 and C5aR1 signaling pathways play a vital role during I/R brain injury in rats.•Schisantherin A modulates neuron injury in parietal cortex of rats after I/R.•Schisantherin A protects brain impairment by regulating TLR4 and C5aR1 after I/R. 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/R 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/R and support the development of schisantherin A as a potential treatment for ischemic stroke.