Physcion Protects Rats Against Cerebral Ischemia-Reperfusion Injury via Inhibition of TLR4/NF-kB Signaling Pathway

Abstract

Xiaobo Dong,* Lei Wang,* Guangrong Song, Xu Cai, Wenxin Wang, Jiaqi Chen, Gesheng Wang The Third Department of Encephalopathy, Dongfang Hospital Beijing University of Chinese Medicine, Beijing 100078, People’s Republic of China*These authors contributed equally to this workCorrespondence: Gesheng WangThe Third Department of Encephalopathy, Dongfang Hospital Beijing University of Chinese Medicine, No. 6 Zone 1 Fangxingyuan, Fangzhuang, Fengtai District, Beijing 100078, People’s Republic of ChinaEmail [email protected]: Ischemic stroke (IS) is characterized by the rapid loss of brain function due to ischemia. Physcion has been found to have a neuroprotective effect against cerebral ischemia-reperfusion (I/R) injury. However, the mechanism by which physcion regulates cerebral I/R injury remains largely unknown.Methods: An oxygen-glucose deprivation/reperfusion (OGD/R) model in SH-SY5Y cells and a rat cerebral ischemia-reperfusion (I/R) model were established, respectively. CCK-8 and flow cytometry assays were used to detect the viability and apoptosis of SH-SY5Y cells. Moreover, enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of SOD, MDA, GSH-Px, TNF-α, IL-1β, IL-6 and IL-10 in the supernatant of SH-SY5Y cells. Meanwhile, Western blot assay was used to detect the expressions of TLR4, p-p65 and p-IκB in SH-SY5Y cells and I/R rats.Results: In this study, physcion treatment significantly rescued OGD/R-induced neuronal injury. In addition, physcion decreased inflammatory response in SH-SY5Y cells after OGD/R insult, as shown by the decreased levels of the pro-inflammatory factors TNF-α, IL-1β, IL-6 and IL-10. Moreover, physcion attenuated the oxidative stress in OGD/R-treated SY-SY5Y cells, as evidenced by the increased SOD and GSH levels and the decreased ROS and MDA levels. Meanwhile, physcion significantly reduced cerebral infarction, attenuated neuronal injury and apoptosis in I/R rats. Furthermore, physcion markedly decreased the expressions of TLR4, p-NF-κB p65 and p-IκB in the brain tissues of rats subjected to I/R and in SH-SY5Y cells exposed to OGD/R.Conclusion: In conclusion, our study indicated that physcion protected neuron cells against I/R injury in vitro and in vivo by inhibition of the TLR4/NF-kB pathway; thus, physcion might serve as a promising therapeutic candidate for IS.Keywords: stroke, ischemia-reperfusion injury, physcion, NF-κB

Keywords

• stroke
• ischemia-reperfusion injury
• physcion
• nf-κb.