Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, Hunan Province Clinical Research Center for Accurate Diagnosis and Treatment of High-incidence Sexually Transmitted Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hunan, China.
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.
J Ethnopharmacol. 2025 Jan 30;337(Pt 2):118898. doi: 10.1016/j.jep.2024.118898. Epub 2024 Oct 5.
Jiao-tai-wan (JTW) is a traditional Chinese herbal prescription, exerts its therapeutic effects on type 2 diabetes mellitus (T2DM). However, its mechanisms and active components remain unclear.
To investigate the therapeutic mechanisms of JTW in treating type 2 diabetes mellitus (T2DM), focusing on identifying active components, their targets, and validating efficacy through SRC/PI3K/AKT signaling pathway modulation in vitro and in vivo.
Active ingredients were retrieved from the Traditional Chinese Medicine System Pharmacology (TCMSP) and Comprehensive Traditional Chinese Medicine Database (TCMID). Targets for these components were identified using the ChemMapper database based on 3D structural similarity. T2DM-related genes were sourced from the DisGeNET and Gene Expression Omnibus (GEO) databases. Protein-protein interaction (PPI) analysis and functional enrichment analysis were conducted to construct a pathway network of "herbs-active ingredients-candidate targets", identifying core molecular mechanisms and key active ingredients. SwissDock was used for molecular docking to predict ligands for candidate targets. The diabetic models were established using C57BL/6 mice and human liver HepG2 cell lines. Their Effectiveness and key molecules were verified through biochemical detection and immunoblotting.
Total 30 active compounds, 597 active ingredient targets, 9631 T2DM-related genes, and 521 overlapping candidate targets were found for JTW on T2DM. Go enrichment indicated the core pathways enriched on insulin and glucose metabolism. The auto-docking demonstrated SRC has potential binds to ingredients of JTW. In vivo, JTW can reduce blood glucose, and blood lipid levels, and HOMA-IR, and increase HOMA-ISI levels in T2DM mice with reduced ALT, AST, MDA levels and increased SOD levels. Meanwhile, decreased phosphorylation of SRC, along with increased levels of phosphorylated PI3K, PI3K, and phosphorylated AKT, were observed. HE staining of liver tissues further confirmed that JTW administration improved liver morphology, reducing inflammation and necrosis. In vitro, JTW significantly ameliorates upstream dysregulation by reducing SRC phosphorylation while enhancing phosphorylated PI3K, PI3K, and AKT phosphorylation levels.
JTW may alleviate glucose, insulin resistance, and lipid metabolism disorders by the SRC/PI3K/AKT signaling pathway, that provide a novel view of potential active compounds and essential targets in treating T2DM.
焦泰丸（JTW）是一种传统的中药方剂，对 2 型糖尿病（T2DM）有治疗作用。然而，其机制和有效成分仍不清楚。
研究 JTW 治疗 2 型糖尿病（T2DM）的治疗机制，重点是鉴定活性成分、其靶标，并通过体外和体内 SRC/PI3K/AKT 信号通路的调节来验证其疗效。
从中药系统药理学（TCMSP）和中药综合数据库（TCMID）中检索活性成分。利用 ChemMapper 数据库基于 3D 结构相似性鉴定这些成分的靶标。从 DisGeNET 和基因表达综合数据库（GEO）中获取与 T2DM 相关的基因。进行蛋白质-蛋白质相互作用（PPI）分析和功能富集分析，构建“草药-活性成分-候选靶标”的通路网络，确定核心分子机制和关键活性成分。利用 SwissDock 进行分子对接，预测候选靶标的配体。使用 C57BL/6 小鼠和人肝 HepG2 细胞系建立糖尿病模型。通过生化检测和免疫印迹验证其疗效和关键分子。
在 T2DM 上，共发现 JTW 有 30 种活性化合物、597 种活性成分靶标、9631 个 T2DM 相关基因和 521 个重叠候选靶标。GO 富集分析表明，胰岛素和葡萄糖代谢富集的核心通路。自动对接表明 SRC 与 JTW 的成分有潜在结合。在体内，JTW 可降低 T2DM 小鼠的血糖、血脂水平和 HOMA-IR，增加 HOMA-ISI 水平，同时降低 ALT、AST、MDA 水平，增加 SOD 水平。同时，观察到 SRC 的磷酸化减少，以及磷酸化 PI3K、PI3K 和磷酸化 AKT 的水平增加。肝组织的 HE 染色进一步证实，JTW 可改善肝脏形态，减轻炎症和坏死。体外实验表明，JTW 通过降低 SRC 磷酸化水平，同时增强磷酸化 PI3K、PI3K 和 AKT 磷酸化水平，显著改善上游失调。
JTW 可能通过 SRC/PI3K/AKT 信号通路缓解葡萄糖、胰岛素抵抗和脂质代谢紊乱，为治疗 T2DM 提供了潜在活性化合物和关键靶标的新视角。
