Zhang Chongyang, Zhu Yindi, Wang Min, Chen Rongchang, Sun Xiaobo
Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China; School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, China.
Academy of Chinese Materia Medica, Wenzhou Medical University, Wenzhou, China.
J Ethnopharmacol. 2025 Jan 30;337(Pt 1):118827. doi: 10.1016/j.jep.2024.118827. Epub 2024 Sep 16.
Astragali Radix (AR) is a traditional Chinese herbal medicine, which has been widely used on treating chronic heart failure (CHF) in clinical practice. Two main types of AR in the market are the imitation wild AR (5YAR) and transplanted AR (2YAR). It remains unclear whether there are variations in the anti-heart failure effects of AR with different growth years. Further research is required to explore the material composition and mechanisms of AR in combating heart failure.
The aim of the study was to compare the main chemical composition content and the protective effects of 2YAR and 5YAR on heart failure.
Ethanol extracts of 2YAR and 5YAR were prepared, and chemical composition analysis was conducted. C57BL/6 mice were subcutaneously injected with ISO to induce heart failure (HF) and were administrated with a corresponding dose of the extracts of 2YAR and 5YAR by gavage for 28 days. Cardiac function was evaluated using echocardiography. The serum levels of enzymes related to myocardial injury, oxidative stress, and inflammation were detected. The left ventricle was excised for hematoxylin-eosin, Masson, Sirius Red, wheat germ agglutinin, and TUNEL staining. Electron microscopy examination of mitochondrial structure in myocardial cells. Protein expression of monocarboxylate transporter 4 (MCT4), Peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), phosphorylated AMP-activated protein kinase (p-AMPK), phosphorylated serine/threonine protein kinase (p-AKT), and phosphorylated insulin receptor substrates 1 (p-IRS-1) were detected by immunohistochemistry and Western blot.
The content of saponins and flavonoids in 5YAR was higher than that in the 2YAR. However, the content of polysaccharides in 5YAR is lower than in 2YAR. The treatment of 2YAR and 5YAR daily for 28 days prevented ISO-induced myocardial damage, including the decrease in serum cardiac enzymes and cardiomyocyte apoptotic index, and improvement in heart function and mitochondrial structure. Additionally, 2YAR and 5YAR reduced serum inflammatory factors and myocardial fibrosis levels. Treatment with 2YAR and 5YAR also decreased MCT4 expression and enhanced PGC-1α, p-AKT, p-AMPK, and p-IRS-1 expression in heart tissues.
The 5YAR was better than 2YAR in anti-heart failure, which may be related to the increase in saponins and flavonoids content. AR exerts anti-heart failure effect by improving mitochondrial function and ameliorating cardiac insulin resistance through activation of the AMPK/PGC1α and IRS/AKT pathways.
黄芪是一种传统的中草药，在临床实践中已被广泛用于治疗慢性心力衰竭（CHF）。市场上的两种主要黄芪类型是仿野生黄芪（5YAR）和移栽黄芪（2YAR）。不同生长年限的黄芪在抗心力衰竭作用方面是否存在差异尚不清楚。需要进一步研究以探索黄芪抗心力衰竭的物质组成和机制。
本研究旨在比较2YAR和5YAR的主要化学成分含量及其对心力衰竭的保护作用。
制备2YAR和5YAR的乙醇提取物，并进行化学成分分析。将C57BL/6小鼠皮下注射异丙肾上腺素（ISO）诱导心力衰竭（HF），并通过灌胃给予相应剂量的2YAR和5YAR提取物，持续28天。使用超声心动图评估心脏功能。检测与心肌损伤、氧化应激和炎症相关的血清酶水平。切除左心室进行苏木精-伊红染色、Masson染色、天狼星红染色、麦胚凝集素染色和TUNEL染色。对心肌细胞线粒体结构进行电子显微镜检查。通过免疫组织化学和蛋白质印迹法检测单羧酸转运蛋白4（MCT4）、过氧化物酶体增殖物激活受体γ共激活因子1α（PGC-1α）、磷酸化的AMP激活蛋白激酶（p-AMPK）、磷酸化的丝氨酸/苏氨酸蛋白激酶（p-AKT）和磷酸化的胰岛素受体底物1（p-IRS-1）的蛋白表达。
5YAR中的皂苷和黄酮含量高于2YAR。然而，5YAR中的多糖含量低于2YAR。每日给予2YAR和5YAR治疗28天可预防ISO诱导的心肌损伤，包括血清心肌酶降低和心肌细胞凋亡指数降低，以及心脏功能和线粒体结构改善。此外，2YAR和5YAR降低了血清炎症因子和心肌纤维化水平。用2YAR和5YAR治疗还降低了心脏组织中MCT4的表达，并增强了PGC-1α、p-AKT、p-AMPK和p-IRS-1的表达。
5YAR在抗心力衰竭方面优于2YAR，这可能与皂苷和黄酮含量增加有关。黄芪通过激活AMPK/PGC1α和IRS/AKT途径改善线粒体功能和减轻心脏胰岛素抵抗，从而发挥抗心力衰竭作用。
