Nursing School, Anhui University of Chinese Medicine, Hefei, P.R. China.
School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, P.R. China.
J Food Biochem. 2021 Jul;45(7):e13757. doi: 10.1111/jfbc.13757. Epub 2021 May 25.
Although astragaloside IV protects from acute myocardial infarction (AMI)-induced chronic heart failure (CHF), the underlying mechanism of action is unclear. We determined the potential therapeutic effect of astragaloside IV using molecular docking approaches and validated the findings by the ligation of the left anterior descending (LAD) coronary artery-induced AMI rat model. The interaction between astragaloside IV and myeloid differentiation factor 88 (MyD88) was evaluated by SwissDock. To explore the mechanisms underlying the beneficial effects of astragaloside IV in the LAD coronary artery ligation-induced AMI model, we administered the rats with astragaloside IV for 4 weeks. Hemodynamic indexes were used to evaluate the degree of myocardial injury in model rats. The histopathological changes in myocardium were detected by hematoxylin & eosin (H&E) staining and Masson's staining. Myocardium homogenate contents of collagen I and collagen III were evaluated by ELISA. The level of myocardial hydroxyproline (HYP) was determined by alkaline hydrolysis. Immunohistochemistry was used to examine collagen I. Western blotting was used to examine relevant proteins. As per the molecular docking study results, astragaloside IV may act on MyD88. Furthermore, astragaloside IV improved hemodynamic disorders, alleviated pathological changes, and reduced abnormal collagen deposition and myocardial HYP in vivo. Astragaloside IV significantly reduced the overexpression of TLR4, MyD88, NF-Κb, and TGF-β, which further validated the molecular docking findings. Hence, astragaloside IV ameliorates AMI by reducing inflammation and blocking TLR4/MyD88/NF-κB signaling. These results indicate that astragaloside IV may alleviate AMI. PRACTICAL APPLICATIONS: Astragaloside IV, a small active substance extracted from Astragalus membranaceus, has demonstrated potent protective effects against cardiovascular ischemia/reperfusion, diabetic nephropathy, and other diseases. Molecular docking experiments showed that astragaloside IV might act on the myeloid differentiation factor 88 (MyD88). Astragaloside IV can effectively reduce the overexpression of TLR4, MyD88, and NF-κB p65, indicating that astragaloside IV inhibits inflammation via TLR4/MyD88/NF-κB signaling pathway. These results indicate that astragaloside IV may alleviate acute myocardial infarction.
虽然黄芪甲苷可预防急性心肌梗死（AMI）引起的慢性心力衰竭（CHF），但其作用机制尚不清楚。我们使用分子对接方法确定了黄芪甲苷的潜在治疗效果，并通过结扎左前降支（LAD）冠状动脉诱导的 AMI 大鼠模型验证了这一发现。用 SwissDock 评估黄芪甲苷与髓样分化因子 88（MyD88）的相互作用。为了探讨黄芪甲苷在 LAD 冠状动脉结扎诱导的 AMI 模型中的有益作用的机制，我们用黄芪甲苷对大鼠进行了 4 周的治疗。血流动力学指标用于评估模型大鼠心肌损伤程度。苏木精和伊红（H&E）染色和 Masson 染色检测心肌组织学变化。ELISA 法检测心肌胶原 I 和胶原 III 含量。碱水解法测定心肌羟脯氨酸（HYP）含量。免疫组化法检测胶原 I。Western blot 法检测相关蛋白。根据分子对接研究结果，黄芪甲苷可能作用于 MyD88。此外，黄芪甲苷改善了体内血流动力学障碍，减轻了病理变化，减少了异常胶原沉积和心肌 HYP。黄芪甲苷显著降低了 TLR4、MyD88、NF-κB 和 TGF-β 的过度表达，进一步验证了分子对接结果。因此，黄芪甲苷通过减轻炎症和阻断 TLR4/MyD88/NF-κB 信号通路改善 AMI。这些结果表明，黄芪甲苷可能减轻 AMI。实际应用：黄芪甲苷是从黄芪中提取的一种具有活性的小分子物质，对心血管缺血再灌注、糖尿病肾病等疾病具有较强的保护作用。分子对接实验表明，黄芪甲苷可能作用于髓样分化因子 88（MyD88）。黄芪甲苷能有效降低 TLR4、MyD88 和 NF-κB p65 的过度表达，表明黄芪甲苷通过 TLR4/MyD88/NF-κB 信号通路抑制炎症。这些结果表明，黄芪甲苷可能减轻急性心肌梗死。
