Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
Guangxi Key Laboratory of Comprehensive Utilization Technology of Pseudo-Ginseng, Guangxi Zhongheng Innovative Pharmaceutical Research CO., LTD, Guangxi, 530032, China.
Biomed Pharmacother. 2021 Apr;136:111287. doi: 10.1016/j.biopha.2021.111287. Epub 2021 Jan 20.
Morbidity and mortality from acute myocardial infarction (AMI) remains substantial although interventional coronary reperfusion strategies are widely use and successful. MI remains the most common cause of heart failure (HF) worldwide. Here we demonstrated that Panax Notoginseng saponins (PNS), the extract of Panax notoginseng, exerts cardioprotective effect in AMI and the underlying mechanism refers to inducing cardiomyocyte autophagy, antiplatelet aggregation, enhancing endothelial migration and angiogenesis. PNS was initially tested to rescue the myocardial infarct size and cardiac function in left anterior descending (LAD) ligation-operated mice to mimic AMI. RNA-seq to profile transcriptome changes in the heart by treatment with PNS were then conducted. PNS and its main constituents Rg1 and Rd directly inhibited platelet aggregation of healthy subjects with VerifyNow Aspirin and P2Y12 assays but less affecting on coagulation compared with dual-antiplatelet (DAPT). In addition, wound healing scratch assay and heart staining demonstrated that PNS and its main constituents Rg1 and R1 significant enhanced the migration of endothelial cells and angiogenesis in response to MI injury. Interestingly, PNS rather than its constituents enhanced glucose deprivation (GD)-induced autophagy through phosphorylation of AMPK Thr172 and CaMKII Thr287 in cardiomyocytes. These findings provide new insights for drug development from natural products like PNS against ischemia heart diseases and HF post MI.
虽然介入性冠状动脉再灌注策略得到广泛应用并取得成功，但急性心肌梗死（AMI）的发病率和死亡率仍然很高。MI 仍然是全球范围内心力衰竭（HF）的最常见原因。在这里，我们证明了三七总皂苷（PNS），即三七的提取物，对 AMI 具有心脏保护作用，其潜在机制涉及诱导心肌细胞自噬、抗血小板聚集、增强内皮细胞迁移和血管生成。最初，PNS 被测试用于挽救左前降支（LAD）结扎操作模拟 AMI 小鼠的心肌梗死面积和心脏功能。然后通过用 PNS 处理对心脏进行转录组变化的 RNA-seq 进行分析。PNS 及其主要成分 Rg1 和 Rd 通过 VerifyNow Aspirin 和 P2Y12 测定直接抑制健康受试者的血小板聚集，但与双重抗血小板（DAPT）相比，对凝血的影响较小。此外，划痕愈合试验和心脏染色表明，PNS 及其主要成分 Rg1 和 R1 显著增强了内皮细胞的迁移和对 MI 损伤的血管生成。有趣的是，PNS 而不是其成分通过磷酸化 AMPK Thr172 和 CaMKII Thr287 在心肌细胞中增强葡萄糖剥夺（GD）诱导的自噬。这些发现为开发天然产物（如 PNS）治疗缺血性心脏病和 MI 后 HF 提供了新的思路。
