**Background:** Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia, insulin resistance, and insufficient insulin secretion, affecting approximately 11.2% of adults in China (2015–2017 survey). While Western medications are first-line treatments, they can cause adverse effects such as liver/kidney damage, hypoglycemia, and obesity. Traditional Chinese medicine (TCM) compounds like Jiaotai Pill—comprising Rhizoma Coptidis (Coptis chinensis) and Cinnamomum cassia—offer multi-target therapeutic potential. This study employs network pharmacology to systematically investigate the active ingredients and molecular mechanisms of Jiaotai Pill in T2DM treatment.
**Methods:** Active components of Jiaotai Pill were identified using the TCMSP database (oral bioavailability ≥30%, drug-likeness ≥0.18) and BATMAN-TCM database (Score cutoff ≥20, P≤0.05), supplemented by literature mining. A total of 21 active ingredients were selected (13 from Coptis chinensis, 8 from Cinnamomum cassia). Protein targets were predicted via PharmMapper and normalized using UniProt (restricted to 'Reviewed (Swiss-Prot)' and 'Homo sapiens'). T2DM-related targets were obtained from GeneCards, OMIM, DrugBank, PharmGKB, and Therapeutic Target Database. Intersection targets were identified using Venny 2.1. A protein–protein interaction (PPI) network was constructed using STRING (highest confidence >0.9) and Cytoscape V3.9.0, with core targets screened via the MCC algorithm. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed using Bioconductor and R language (P<0.05, q<0.05).
**Key Results:** Database screening yielded 21 active components and 262 potential targets for Jiaotai Pill, of which 89 overlapped with T2DM-related targets. The active ingredient-T2DM target network contained 105 nodes and 196 edges (average degree 3.7). Core active ingredients with degree >7.4 included quercetin, (-)-epigallocatechin-3-gallate (EGCG), kaempferol, hydroberberine, stigmasterol, berberine, and palmatine. PPI network analysis identified 61 nodes and 396 edges, with the top 20 core targets including CCND1 (MCC 3426), CDK4 (3384), CDK1 (3252), CDK2 (3006), CDKN1A (2694), RB1 (2406), CDK6 (2160), TP53 (1020), CCNB1 (846), and CDKN1C (720). GO enrichment analysis revealed 1690 biological process entries (e.g., response to peptide, regulation of membrane potential), 106 molecular function entries (e.g., DNA-transcription factor binding, ubiquitin-like protein ligase binding), and 78 cellular component entries (e.g., lipid rafts, membrane microdomains, transcription regulator complexes). KEGG analysis identified 124 pathways, with key T2DM-related pathways including the AGE-RAGE signaling pathway, PI3K-AKT signaling pathway, endocrine resistance pathway, TNF signaling pathway, and Toll-like receptor signaling pathway.
**Clinical Implications:** This network pharmacology analysis suggests that Jiaotai Pill exerts therapeutic effects on T2DM through multiple active ingredients, multiple targets, and multiple pathways. Key mechanisms include improving insulin resistance via PI3K-AKT signaling, reducing chronic inflammation through TNF and Toll-like receptor pathways, and inhibiting diabetic complications via the AGE-RAGE axis. The study provides a theoretical foundation for clinical use of Jiaotai Pill in T2DM and supports further experimental validation. However, as a network pharmacology review, these findings require confirmation through in vitro, in vivo, and clinical studies.