State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
Department of Cardiovascular Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
Front Endocrinol (Lausanne). 2022 Jul 7;13:918469. doi: 10.3389/fendo.2022.918469. eCollection 2022.
Management of menopausal dyslipidemia is the main measure to reduce the incidence of cardiovascular disease in postmenopausal women. Tonifying Kidney and Removing Dampness Formula (TKRDF) is a traditional Chinese medicine (TCM) formula that ameliorates dyslipidemia in postmenopausal women. This study applied network pharmacology, molecular docking, and and experiments to investigate the underlying mechanism of TKRDF against postmenopausal dyslipidemia.
Network pharmacology research was first conducted, and the active compounds and targets of TKRDF, as well as the targets of postmenopausal dyslipidemia, were extracted from public databases. Protein-protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to identify the potential targets and signaling pathways of TKRDF in postmenopausal dyslipidemia. Molecular docking was then performed to evaluate the combination of active compounds with principal targets. Finally, an ovariectomized rat model was used for the experiment and alpha mouse liver 12 (AML12) cells treated with palmitic acid were used for the experiments to provide further evidence for the research.
Based on network pharmacology analysis, we obtained 78 active compounds from TKRDF that acted on 222 targets of postmenopausal dyslipidemia. The analysis results indicated that IL6, TNF, VEGFA, AKT1, MAPK3, MAPK1, PPARG and PIK3CA, etc., were the potentially key targets, and the PI3K/AKT signaling pathway was the possibly crucial pathway for TKRDF to treat postmenopausal dyslipidemia. Molecular docking suggested that the active compounds have good binding activity with the core targets. The and experiments demonstrated that TKRDF ameliorates postmenopausal dyslipidemia by regulating hormone levels, inhibiting inflammation, promoting angiogenesis and inhibiting lipid synthesis, which appear to be related to TKRDF's regulation of the ERK1/2 and PI3K/AKT signaling pathways.
This study clarified the active ingredients, potential targets, and molecular mechanisms of TKRDF for treating postmenopausal dyslipidemia. It also provided a feasible method to uncover the scientific basis and therapeutic mechanism for prescribing TCM in the treatment of diseases.
绝经后血脂异常的管理是降低绝经后女性心血管疾病发病率的主要措施。补肾祛湿方（TKRDF）是一种中药方剂，可改善绝经后妇女的血脂异常。本研究应用网络药理学、分子对接和实验研究，探讨 TKRDF 治疗绝经后血脂异常的潜在机制。
首先进行网络药理学研究，从公共数据库中提取 TKRDF 的活性化合物和靶点，以及绝经后血脂异常的靶点。采用蛋白质-蛋白质相互作用（PPI）、基因本体（GO）和京都基因与基因组百科全书（KEGG）通路分析，鉴定 TKRDF 治疗绝经后血脂异常的潜在靶点和信号通路。然后进行分子对接，评估活性化合物与主要靶点的结合情况。最后，采用去卵巢大鼠模型和棕榈酸处理的 alpha 小鼠肝 12（AML12）细胞进行实验，为研究提供进一步证据。
基于网络药理学分析，从 TKRDF 中获得 78 种作用于绝经后血脂异常 222 个靶点的活性化合物。分析结果表明，IL6、TNF、VEGFA、AKT1、MAPK3、MAPK1、PPARG 和 PIK3CA 等可能是关键靶点，PI3K/AKT 信号通路可能是 TKRDF 治疗绝经后血脂异常的关键通路。分子对接表明，活性化合物与核心靶点具有良好的结合活性。实验研究表明，TKRDF 通过调节激素水平、抑制炎症、促进血管生成和抑制脂质合成来改善绝经后血脂异常，这似乎与 TKRDF 对 ERK1/2 和 PI3K/AKT 信号通路的调节有关。
本研究阐明了 TKRDF 治疗绝经后血脂异常的活性成分、潜在靶点和分子机制，为揭示 TCM 治疗疾病的科学依据和治疗机制提供了可行的方法。
