苦参碱
苦参
药理学
细胞凋亡
车站3
机制(生物学)
再灌注损伤
医学
药代动力学
化学
缺血
生物化学
内科学
哲学
认识论
精神科
作者
Kai Zhou,Hua Chen,Xiaoyu Wang,Yan-mei Xu,Yu-feng Liao,Yuan-yuan Qin,Xue-wan Ge,Tingting Zhang,Zhong-lin Fang,Binying Fu,Qingzhong Xiao,Feng-qin Zhu,Sirui Chen,Xuesheng Liu,Qi-chao Luo,Shan Gao
标识
DOI:10.1016/j.biopha.2022.113792
摘要
Xin-Ji-Er-Kang (XJEK) is traditional Chinese formula presented excellent protective effects on several heart diseases, but the potential components and targets are still unclear. The aim of this study is to elucidate the effective components of XJEK and reveal its potential mechanism of cardioprotective effect in myocardial ischemia-reperfusion (MIR) injury.Firstly, the key compounds in XJEK, plasma and heart tissue were analyzed by high resolution mass spectrometry. Bioinformatics studies were also involved to disclose the potential targets and the binding sites for the key compounds. Secondly, to study the protective effect of XJEK on MIR injury and related mechanism, mice subjected to MIR surgery and gavage administered with XJEK for 6 weeks. Cardiac function parameters and apoptosis level of cardiac tissue were assessed. The potential mechanism was further verified by knock down of target protein in vitro.Pharmacokinetics studies showed that Sophora flavescens alkaloids, primarily composed with matrine, are the key component of XJEK. And, through bioinformatic analysis, we speculated JAK2 could be the potential target for XJEK, and could form stable hydrogen bonds with matrine. Administration of XJEK and matrine significantly improved heart function and reduced apoptosis of cardiomyocytes by increasing the phosphorylation of JAK2 and STAT3. The anti-apoptosis effect of XJEK and matrine was also observed on AC16 cells, and could be reversed by co-treatment with JAK2 inhibitor AG490 or knock-down of JAK2.XJEK exerts cardioprotective effect on MIR injury, which may be associated with the activation of JAK2/STAT3 signaling pathway.
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