Altern Ther Health Med. 2024 Nov;30(11):354-368.
A traditional Chinese medicine (TCM) formula, containing Astragalus membranaceus (Fisch.) Bunge, Aconitum wilsonii Stapf ex Veitch, Curcuma longa L., and Radix ophiopogonis (AACO), has therapeutic value for the treatment of chronic heart failure (CHF).
This study intends to explore the pharmacological mechanism underlying the activity of the AACO formula against CHF.
Using the TCM Systems Pharmacology database and Bioinformatics Analysis Tool for Molecular Mechanism of TCM, the active ingredients contained in the herbs of the AACO formula were screened. Meanwhile, the target genes related to these active ingredients were identified and genes correlated with CHF were screened. Protein-protein interaction networks were built to elucidate the relationships between the AACO formula and CHF. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway enrichment analysis were carried out using the DAVID database. A "drug-component-target-disease" network was constructed with Cytoscape 3.7.0. The therapeutic effect of the AACO formula was proven by hemodynamic study, echocardiography evaluation, and histological analysis in transverse aortic constriction-induced CHF mice and was validated in vitro.
A total of 105 active ingredients and 1026 related targets were screened and identified, and 240 related targets overlapping with CHF were selected. According to GO analysis, the enriched genes participated in gene expression and cardiac contraction regulation by Ca2+ regulation. From KEGG analysis, the calcium axis was identified as one of the main mechanisms through which the AACO formula exerts an anti-CHF effect. AACO was validated to significantly improve cardiac diastolic and systolic functions in vivo via an increase in the rate of Ca2+ reuptake of the myocardial sarcoplasmic reticulum and improved myocardial contractility in vitro.
Network pharmacology is a convenient method to study the complex pharmacological mechanisms of TCM. The calcium axis likely participates in the anti-CHF mechanism of AACO.
含有黄芪、乌头、姜黄和麦冬的中药配方对治疗慢性心力衰竭（CHF）具有治疗价值。
本研究旨在探讨 AACO 配方治疗 CHF 的药理机制。
使用中药系统药理学数据库和中药分子机制生物信息学分析工具，筛选 AACO 配方中草药的活性成分。同时，鉴定与这些活性成分相关的靶基因，并筛选与 CHF 相关的基因。构建蛋白质-蛋白质相互作用网络，阐明 AACO 配方与 CHF 之间的关系。使用 DAVID 数据库进行基因本体（GO）和京都基因与基因组百科全书（KEGG）信号通路富集分析。使用 Cytoscape 3.7.0 构建“药物-成分-靶标-疾病”网络。通过横主动脉缩窄诱导的 CHF 小鼠的血液动力学研究、超声心动图评估和组织学分析以及体外验证，证明了 AACO 配方的治疗效果。
筛选和鉴定出 105 种活性成分和 1026 个相关靶标，选择了 240 个与 CHF 重叠的相关靶标。根据 GO 分析，富集的基因参与了基因表达和心肌收缩的调节。从 KEGG 分析中发现，钙轴是 AACO 发挥抗 CHF 作用的主要机制之一。体内实验表明，AACO 可通过增加心肌肌浆网 Ca2+摄取率显著改善心脏舒张和收缩功能，体外实验表明，AACO 可改善心肌收缩力。
网络药理学是研究中药复杂药理机制的一种便捷方法。钙轴可能参与 AACO 的抗 CHF 机制。
