School of Pharmaceutical Sciences, Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.
Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangzhou, China.
Pharm Biol. 2022 Dec;60(1):255-273. doi: 10.1080/13880209.2022.2025859.
Xinbao pill (XBW), a traditional Chinese herbal formula, is widely used in clinical treatment for cardiovascular diseases; however, the therapeutic effect of XBW on myocardial ischaemia-reperfusion injury (MI/RI) is unclear.
This study evaluates the cardioprotective effect and molecular mechanism of XBW against MI/RI.
A phytochemistry-based network pharmacology analysis was used to uncover the mechanism of XBW against MI/RI. Ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry method was used to identify chemicals. MI/RI-related targets of XBW were predicted using TargetNet database, OMIC database, etc. Sprague-Dawley (SD) rats under anterior descending artery ligation model were divided into Sham, MI/RI and XBW (180 mg/kg, intragastric administration). After 30 min ischaemia and 24 h reperfusion, heart tissues were collected for measurement of myocardial infarct size. After oxygen glucose deprivation for 6 h, H9c2 cells were treated with XBW (60, 240 and 720 μg/mL) and diazoxide (100 μM) for 18 h of reperfusion.
Thirty-seven chemicals were identified in XBW; 50 MI/RI-related targets of XBW were predicted using indicated databases. XBW significantly reduced infarct size and creatine kinase MB (CK-MB) level after MI/RI; XBW protected H9c2 cells against OGD/R injury. Gene ontology (GO) and KEGG pathway enrichment analyses by String database showed that the cardioprotective effect of XBW was associated with autophagy and apoptosis signalling pathways. Experimental investigation also verified that XBW suppressed apoptosis, autophagy and endoplasmic reticulum (ER) stress.
XBW showed therapeutic effects against MI/RI mainly via attenuating apoptosis though suppressing excessive autophagy and ER stress.
心宝丸（XBW）是一种传统的中草药配方，广泛用于心血管疾病的临床治疗；然而，XBW 对心肌缺血再灌注损伤（MI/RI）的治疗效果尚不清楚。
本研究评估了 XBW 对 MI/RI 的心脏保护作用及其分子机制。
基于植物化学的网络药理学分析用于揭示 XBW 对 MI/RI 的作用机制。采用超高效液相色谱-四极杆飞行时间质谱法鉴定化学成分。使用 TargetNet 数据库、OMIC 数据库等预测 XBW 对 MI/RI 的相关靶点。采用结扎大鼠前降支模型将 Sprague-Dawley（SD）大鼠分为假手术组、MI/RI 组和 XBW（180mg/kg，灌胃）组。缺血 30min 再灌注 24h 后，取心脏组织测量心肌梗死面积。缺氧葡萄糖剥夺 6h 后，用 XBW（60、240 和 720μg/mL）和二氮嗪（100μM）处理 H9c2 细胞 18h 再灌注。
在 XBW 中鉴定出 37 种化学成分；使用上述数据库预测 XBW 对 MI/RI 的 50 个相关靶点。XBW 可显著降低 MI/RI 后梗死面积和肌酸激酶 MB（CK-MB）水平；XBW 可保护 H9c2 细胞免受 OGD/R 损伤。STRING 数据库的基因本体（GO）和 KEGG 通路富集分析表明，XBW 的心脏保护作用与自噬和细胞凋亡信号通路有关。实验研究还证实，XBW 通过抑制过度自噬和内质网（ER）应激来抑制细胞凋亡。
XBW 对 MI/RI 的治疗作用主要通过抑制凋亡来发挥作用，同时抑制过度自噬和 ER 应激。
