Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, 230038, Anhui, People's Republic of China.
School of Graduate, Anhui University of Chinese Medicine, Hefei, 230012, Anhui, People's Republic of China.
Sci Rep. 2024 Sep 27;14(1):22319. doi: 10.1038/s41598-024-73642-y.
Diabetes mellitus (DM) is a chronic metabolic disease that is highly susceptible to kidney injury. Di'ao XinXueKang capsules (DXXK) is a novel Chinese herbal medicine that has been used in clinical trials for the therapy of DM and kidney disease, but the underlying pharmacological mechanism remains unclear. This study aims to integrate network pharmacology, molecular docking and in vivo experiments to explore the potential mechanisms of DXXK in the treatment of diabetic kidney injury. The chemical constituents of DXXK were extracted from the ETCM and Batman-TCM databases, and then evaluated for their pharmacological activity via the Swiss ADME platform. Multiple disease databases were searched and integrated for DM-related targets. Overlapping targets were then collected to construct a protein-protein interaction (PPI) network. KEGG and GO enrichment analyses were performed based on the Metascape database, and molecular docking was performed using AutoDock Vina software. The main components in DXXK were analyzed by HPLC. The results of network pharmacology and molecular docking were validated in an animal model of DM induced by the combination of a high-fat diet (HFD) and streptozotocin (STZ). We screened and obtained 7 ingredients and identified dioscin, protodioscin, and pseudoprotodioscin as the major components of DXXK by HPLC. A total of 2,216 DM-related pathogenic genes were obtained from DrugBank, GeneCards, OMIM, and DisGeNET databases. KEGG and GO enrichment analyses indicated that the TGF-beta signaling pathway is a critical pathway associated with DM therapy. Molecular docking revealed that the ingredients in DXXK bind to the pivotal targets TGFβ1, Smad2, and Smad3. In diabetic mice, we found that DXXK alleviated diabetic symptoms, lowered blood glucose, improved insulin tolerance, and modulated lipid metabolism. Furthermore, DXXK attenuated renal lesions and fibrosis by downregulating TGFβ1, Smad2, and Smad3. Collectively, our results suggest that DXXK has the potential to regulate glucolipid metabolism in DM, and it may serve as a viable therapeutic option for renoprotection by inhibiting of the TGF-β1/Smad2/3 pathway.
糖尿病（DM）是一种易发生肾脏损伤的慢性代谢性疾病。地奥心血康胶囊（DXXK）是一种新型中药，已在临床试验中用于治疗糖尿病和肾病，但潜在的药理机制尚不清楚。本研究旨在整合网络药理学、分子对接和体内实验，探讨 DXXK 治疗糖尿病肾病的潜在机制。从 ETCM 和 Batman-TCM 数据库中提取 DXXK 的化学成分，并通过 Swiss ADME 平台评估其药理活性。从多个疾病数据库中搜索并整合与 DM 相关的靶点。然后收集重叠靶点构建蛋白质-蛋白质相互作用（PPI）网络。基于 Metascape 数据库进行 KEGG 和 GO 富集分析，并使用 AutoDock Vina 软件进行分子对接。采用高效液相色谱法（HPLC）分析 DXXK 中的主要成分。通过高脂饮食（HFD）和链脲佐菌素（STZ）联合诱导的 DM 动物模型验证网络药理学和分子对接的结果。我们筛选并获得 7 种成分，并通过 HPLC 鉴定地奥心血康胶囊中的主要成分为薯蓣皂苷元、原薯蓣皂苷和伪原薯蓣皂苷。从 DrugBank、GeneCards、OMIM 和 DisGeNET 数据库中获得 2216 个与 DM 相关的致病基因。KEGG 和 GO 富集分析表明，TGF-β 信号通路是与 DM 治疗相关的关键通路。分子对接表明 DXXK 中的成分与关键靶点 TGFβ1、Smad2 和 Smad3 结合。在糖尿病小鼠中，我们发现 DXXK 可缓解糖尿病症状、降低血糖、改善胰岛素耐量和调节脂代谢。此外，DXXK 通过下调 TGFβ1、Smad2 和 Smad3 减轻肾脏病变和纤维化。综上所述，本研究结果表明 DXXK 具有调节 DM 中糖脂代谢的潜力，可能通过抑制 TGF-β1/Smad2/3 通路成为一种有前途的肾脏保护治疗选择。
