State-local Joint Engineering Research Center of Ginseng Breeding and Application (Jilin), Jilin Agricultural University, Changchun, China.
Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, China; and.
J Cardiovasc Pharmacol. 2021 Nov 1;78(5):e690-e702. doi: 10.1097/FJC.0000000000001119.
This study aimed to investigate the effects of protopanaxadiol and protopanaxatriol ginsenosides on aconitine-induced cardiomyocyte injury and their regulatory mechanisms. The effects of ginsenosides on aconitine-induced cardiomyocyte damage were initially evaluated using H9c2 cells, and the molecular mechanisms were elucidated using molecular docking and western blotting. The changes in enzyme content, reactive oxygen species (ROS), calcium (Ca2+) concentration, and apoptosis were determined. Furthermore, an aconitine-induced cardiac injury rat model was established, the cardiac injury and serum physiological and biochemical indexes were measured, and the effects of ginsenoside were observed. The results showed that ginsenoside Rb1 significantly increased aconitine-induced cell viability, and its binding conformation with protein kinase B (AKT) protein was the most significant. In vitro and in vivo, Rb1 protects cardiomyocytes from aconitine-induced injury by regulating oxidative stress levels and maintaining Ca2+ concentration homeostasis. Moreover, Rb1 activated the PI3K/AKT pathway, downregulated Cleaved caspase-3 and Bax, and upregulated Bcl-2 expression. In conclusion, Rb1 protected H9c2 cells from aconitine-induced injury by maintaining Ca2+ homeostasis and activating the PI3K/AKT pathway to induce a cascade response of downstream proteins, thereby protecting cardiomyocytes from damage. These results suggested that ginsenoside Rb1 may be a potential cardiac protective drug.
本研究旨在探讨原人参二醇和原人参三醇型人参皂苷对乌头碱诱导的心肌细胞损伤的影响及其调控机制。首先采用 H9c2 细胞评价了皂苷对乌头碱诱导的心肌细胞损伤的作用,并用分子对接和 Western blot 阐明了其分子机制。测定了酶含量、活性氧(ROS)、钙(Ca2+)浓度和细胞凋亡的变化。此外,建立了乌头碱诱导的心肌损伤大鼠模型,测定了心肌损伤和血清生理生化指标,并观察了人参皂苷的作用。结果表明,人参皂苷 Rb1 显著提高了乌头碱诱导的细胞活力,其与蛋白激酶 B(AKT)蛋白的结合构象最为显著。在体外和体内,Rb1 通过调节氧化应激水平和维持 Ca2+浓度稳态来保护心肌细胞免受乌头碱诱导的损伤。此外,Rb1 激活了 PI3K/AKT 通路,下调了 Cleaved caspase-3 和 Bax 的表达,上调了 Bcl-2 的表达。总之,Rb1 通过维持 Ca2+稳态和激活 PI3K/AKT 通路来保护 H9c2 细胞免受乌头碱诱导的损伤,从而诱导下游蛋白的级联反应,保护心肌细胞免受损伤。这些结果表明,人参皂苷 Rb1 可能是一种潜在的心脏保护药物。