Department of Postgraduate, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.
Cardiology Department, Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, China.
Medicine (Baltimore). 2024 Aug 2;103(31):e39104. doi: 10.1097/MD.0000000000039104.
Diabetes mellitus (DM) and heart failure frequently coexist, presenting significant public health challenges. QiShenYiQi Dropping Pills (QSDP) are widely employed in the treatment of diabetes mellitus concomitant with heart failure (DM-HF). Nevertheless, the precise mechanisms underlying their efficacy have yet to be elucidated. Active ingredients and likely targets of QSDP were retrieved from the TCMSP and UniProt databases. Genes associated with DM-HF were pinpointed through searches in the GeneCards, OMIM, DisGeNET, and TTD databases. Differential genes connected to DM-HF were sourced from the GEO database. Enrichment analyses via gene ontology and Kyoto Encyclopedia of Genes and Genomes pathways, as well as immune infiltration assessments, were conducted using R software. Further analysis involved employing molecular docking strategies to explore the interactions between the identified targets and active substances in QSDP that are pertinent to DM-HF treatment. This investigation effectively discerned 108 active compounds and 257 targets relevant to QSDP. A protein-protein interaction network was constructed, highlighting 6 central targets for DM-HF treatment via QSDP. Gene ontology enrichment analysis predominantly linked these targets with responses to hypoxia, metabolism of reactive oxygen species, and cytokine receptor interactions. Analysis of Kyoto Encyclopedia of Genes and Genomes pathways demonstrated that these targets mainly participate in pathways linked to diabetic complications, such as AGE-RAGE signaling, dyslipidemia, arteriosclerosis, the HIF-1 signaling pathway, and the tumor necrosis factor signaling pathway. Further, immune infiltration analysis implied that QSDP's mechanism in treating DM-HF might involve immune-mediated inflammation and crucial signaling pathways. Additionally, molecular docking studies showed that the active substances in QSDP have strong binding affinities with these identified targets. This research presents a new model for addressing DM-HF through the use of QSDP, providing novel insights into incorporating traditional Chinese medicine (TCM) principles in the clinical treatment of DM-HF. The implications of these findings are substantial for both clinical application and further scientific inquiry.
糖尿病(DM)和心力衰竭常同时存在,这对公共健康构成了重大挑战。芪参益气滴丸广泛应用于治疗糖尿病合并心力衰竭(DM-HF)。然而,其确切疗效机制尚未阐明。从 TCMSP 和 UniProt 数据库中检索到芪参益气滴丸的活性成分和可能的靶点。通过在 GeneCards、OMIM、DisGeNET 和 TTD 数据库中搜索,确定与 DM-HF 相关的基因。从 GEO 数据库中获取与 DM-HF 相关的差异基因。使用 R 软件进行基因本体论和京都基因与基因组百科全书途径的富集分析,以及免疫浸润评估。进一步分析包括采用分子对接策略探讨鉴定出的与 DM-HF 治疗相关的 QSDP 活性成分和靶点之间的相互作用。该研究有效识别出 108 种与 QSDP 相关的活性化合物和 257 个靶点。构建蛋白质-蛋白质相互作用网络,通过 QSDP 治疗 DM-HF 的 6 个核心靶点。基因本体论富集分析主要将这些靶点与缺氧反应、活性氧物质代谢和细胞因子受体相互作用联系起来。京都基因与基因组百科全书途径分析表明,这些靶点主要参与与糖尿病并发症相关的途径,如 AGE-RAGE 信号、血脂异常、动脉硬化、HIF-1 信号通路和肿瘤坏死因子信号通路。此外,免疫浸润分析表明,QSDP 治疗 DM-HF 的机制可能涉及免疫介导的炎症和关键信号通路。此外,分子对接研究表明,QSDP 中的活性物质与这些鉴定出的靶点具有很强的结合亲和力。该研究为使用 QSDP 治疗 DM-HF 提供了一种新的模式,为将中药(TCM)原则应用于 DM-HF 的临床治疗提供了新的见解。这些发现对临床应用和进一步的科学研究都具有重要意义。