School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, No. 232, Waihuandong Road, Guangzhou Higher Education Mega Center, Guangzhou, 510006, PR China.
Baiyunshan Pharmaceutical General Factory, Guangzhou Baiyunshan Pharmaceutical Holdings Co., Ltd., Guangzhou, 510515, PR China; Key Laboratory of Key Technology Research on Chemical Raw Materials and Preparations of Guangdong Province, Guangzhou, 510515, PR China.
J Ethnopharmacol. 2022 Jun 28;292:115150. doi: 10.1016/j.jep.2022.115150. Epub 2022 Mar 15.
Cardiac hypertrophy (CH) is maladaptive and contributes to the pathogenesis of heart failure. Huoxin pill (HXP), a Chinese herbal prescription, is widely applied in the treatment of cardiovascular disease (CAD). Its mechanism, however, is unclear.
This study investigated the mechanism of action for Huoxin pill in the treatment of CH, an important stage of CAD.
A total of 60 rats were injected with isoprenaline (ISO) to establish a model of CH. Echocardiography and histopathologic evaluation were performed to evaluate the disease severity, whereas ELISAs were conducted to determine the expression of oxidative stress. Network pharmacology and metabolomic analyses were conducted to identify the key compounds, core targets and pathways that mediate the effects of HXP against CH. Western blotting and immunohistochemistry were used to test apoptosis protein levels.
HXP administration in ISO-treated rats decreased hypertrophy indices, alleviated cardiac pathological damage, and downregulated oxidative stress levels when compared to those of rats subjected to ISO treatment only. Moreover, network pharmacology results suggested that the PI3K-Akt pathway is a main mechanism by which HXP inhibits cardiac hypertrophy, and experimental verification showed that HXP inhibited cardiomyocyte apoptosis via activation of the PI3K-Akt pathway. The results of metabolomic analysis identified 21 differential metabolites between the HXPH group and ISO group, which were considered to be metabolic biomarkers of HXP in the treatment of CH. Among them, 6 differential metabolites were significantly upregulated, and 15 were significantly downregulated.
The present study presents an integrated strategy for investigating the mechanisms of HXP in the treatment of CH and sheds new light on the application of HXP as a traditional Chinese medicine.
心肌肥厚（CH）是一种适应性不良的表现，会导致心力衰竭的发病机制。 活心丸（HXP）是一种中药方剂，广泛用于治疗心血管疾病（CAD）。 然而，其作用机制尚不清楚。
本研究旨在探讨活心丸治疗 CH 的作用机制，CH 是 CAD 的重要阶段。
共 60 只大鼠用异丙肾上腺素（ISO）注射建立 CH 模型。 超声心动图和组织病理学评估用于评估疾病严重程度，而 ELISA 用于确定氧化应激的表达。 进行网络药理学和代谢组学分析，以确定介导 HXP 对 CH 作用的关键化合物、核心靶标和途径。 采用 Western blot 和免疫组织化学法检测凋亡蛋白水平。
与仅接受 ISO 处理的大鼠相比，HXP 给药可降低 ISO 处理大鼠的肥大指数，减轻心脏病理损伤，并降低氧化应激水平。 此外，网络药理学结果表明，PI3K-Akt 通路是 HXP 抑制心肌肥厚的主要机制，实验验证表明 HXP 通过激活 PI3K-Akt 通路抑制心肌细胞凋亡。 代谢组学分析结果确定了 HXPH 组和 ISO 组之间的 21 个差异代谢物，这些代谢物被认为是 HXP 治疗 CH 的代谢标志物。 其中，6 个差异代谢物显著上调，15 个差异代谢物显著下调。
本研究提出了一种综合策略，用于研究 HXP 治疗 CH 的机制，并为 HXP 作为中药的应用提供了新的思路。
