Analysis of Chemical Constituents of Jiaotai Pill Based on UPLC-Q-Exactive Orbitrap-HRMS Technology and Its Antidiabetic Type 2 Mechanism in Network Pharmacology.

INTRODUCTION

Jiaotai Pill (JTP) is a Traditional Chinese Medicine (TCM) prescription that has demonstrated therapeutic effects against Type 2 Diabetes Mellitus (T2DM). However, its active antidiabetic components and underlying mechanism of action remain unclear. This study aimed to identify the bioactive components in JTP and elucidate their molecular targets and therapeutic pathways in T2DM.

METHODS

Chemical components of JTP were identified using ultra-high performance liquid chromatography coupled with Q-Exactive Orbitrap high-resolution mass spectrometer (UHPLC-Q-Exactive Orbitrap-HRMS) in both positive and negative ion modes. Data were processed with Compound Discoverer 3.2 (CD 3.2) data software and validated using literature sources. Network pharmacology analysis was performed via multiple databases, including the Traditional Chinese Medicine Systems Pharmacology Database, Uniport, PubChem, GenCards, String, and Cytoscape, to predict potential bioactive compounds and therapeutic targets. Key interactions were validated using molecular docking and molecular dynamics simulations.

RESULTS

A total of 104 compounds were identified in JTP. Network pharmacology analysis revealed 5 key antidiabetic components and 5 core targets. These targets are involved in biological processes including apoptosis regulation, cell proliferation, and protein phosphorylation, and are enriched in pathways such as neuroactive ligand-receptor interaction, PI3K-AKT signaling, and AGE-RAGE signaling. Molecular docking indicated strong binding affinity between dihydrochelerythrine and AKT1(-9.0 kcal/mol) and TNF-α (-6.7 kcal/mol). Molecular dynamics simulation demonstrated stable and sustained hydrogen bonding between dihydrochelerythrine and AKT1.

DISCUSSION: Dihydrochelerythrine, as an active ingredient in JTP, may exert its antidiabetic mechanism by binding with AKT1, but it needs to be verified by subsequent animal or cell experiments.

CONCLUSION

Dihydrochelerythrine, a key active component of JTP, may exert antidiabetic effects in T2DM through stable interaction with AKT1, highlighting a potential therapeutic mechanism.