Institute of Basic Medical Sciences, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.
Department of Pharmacy, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China.
Sci Rep. 2024 May 27;14(1):12109. doi: 10.1038/s41598-024-61926-2.
Chronic Heart Failure (CHF) is a significant global public health issue, with high mortality and morbidity rates and associated costs. Disease modules, which are collections of disease-related genes, offer an effective approach to understanding diseases from a biological network perspective. We employed the multi-Steiner tree algorithm within the NeDRex platform to extract CHF disease modules, and subsequently utilized the Trustrank algorithm to rank potential drugs for repurposing. The constructed disease module was then used to investigate the mechanism by which Panax ginseng ameliorates CHF. The active constituents of Panax ginseng were identified through a comprehensive review of the TCMSP database and relevant literature. The Swiss target prediction database was utilized to determine the action targets of these components. These targets were then cross-referenced with the CHF disease module in the STRING database to establish protein-protein interaction (PPI) relationships. Potential action pathways were uncovered through Gene Ontology (GO) and KEGG pathway enrichment analyses on the DAVID platform. Molecular docking, the determination of the interaction of biological macromolecules with their ligands, and visualization were conducted using Autodock Vina, PLIP, and PyMOL, respectively. The findings suggest that drugs such as dasatinib and mitoxantrone, which have low docking scores with key disease proteins and are reported in the literature as effective against CHF, could be promising. Key components of Panax ginseng, including ginsenoside rh4 and ginsenoside rg5, may exert their effects by targeting key proteins such as AKT1, TNF, NFKB1, among others, thereby influencing the PI3K-Akt and calcium signaling pathways. In conclusion, drugs like dasatinib and midostaurin may be suitable for CHF treatment, and Panax ginseng could potentially mitigate the progression of CHF through a multi-component-multi-target-multi-pathway approach. Disease module analysis emerges as an effective strategy for exploring drug repurposing and the mechanisms of traditional Chinese medicine in disease treatment.
慢性心力衰竭（CHF）是一个重大的全球公共卫生问题，具有高死亡率和发病率以及相关成本。疾病模块是一组与疾病相关的基因，它提供了一种从生物网络角度理解疾病的有效方法。我们利用 NeDRex 平台中的多 Steiner 树算法提取 CHF 疾病模块，然后利用 Trustrank 算法对潜在的再利用药物进行排名。构建的疾病模块随后用于研究人参改善 CHF 的机制。通过全面审查 TCMSP 数据库和相关文献，确定了人参的活性成分。利用 Swiss target prediction 数据库确定这些成分的作用靶点。然后将这些靶点与 STRING 数据库中的 CHF 疾病模块交叉引用，建立蛋白质-蛋白质相互作用（PPI）关系。通过 DAVID 平台上的基因本体论（GO）和 KEGG 通路富集分析，揭示潜在的作用途径。利用 Autodock Vina、PLIP 和 PyMOL 分别进行分子对接、生物大分子与其配体的相互作用的确定和可视化。研究结果表明，达沙替尼和米托蒽醌等药物具有较低的与关键疾病蛋白的对接评分，并且在文献中被报道对 CHF 有效，可能是有前途的。人参的关键成分，包括人参皂苷 Rh4 和人参皂苷 RG5，可能通过靶向关键蛋白如 AKT1、TNF、NFKB1 等发挥作用，从而影响 PI3K-Akt 和钙信号通路。总之，达沙替尼和 midostaurin 等药物可能适用于 CHF 治疗，而人参可能通过多成分-多靶点-多途径的方法减轻 CHF 的进展。疾病模块分析成为探索药物再利用和传统中药治疗疾病机制的有效策略。
