Mechanistic Exploration of Wendan Decoction in Hyperlipidemia Treatment: An Integrated Network Pharmacology and Metabolomics Analysis
Nan Xu, Jing-wen Ma, Xiao-xue Yin, Ya-nan Xiao, Xin-gang Xu, Lei Ma, Muhammad ljaz, Hai-yan ShiObjective
Wendan Decoction (WDD), a canonical Traditional Chinese Medicine formula with clinical efficacy in hyperlipidemia, lacks systematic characterization of its molecular mechanisms. This study aimed to elucidate WDD’s lipid-lowering mechanisms through an integrated multi-platform strategy.
Methods
The chemical constituents of WDD were characterized using UPLC-QE-Orbitrap-MS. Network pharmacology was performed to identify potential targets and enriched signaling pathways associated with WDD and hyperlipidemia. A high-fat diet-induced rat model was established to evaluate the lipid-lowering effects of WDD by assessing plasma lipid profiles and hepatic histopathology. Untargeted plasma metabolomics was subsequently conducted to identify differential metabolites and associated metabolic pathways. Network pharmacology and metabolomics data were integrated to explore potential mechanisms.
Results
UPLC-QE-Orbitrap-MS identified 186 constituents distributed across six component herbs, comprising 78 flavonoids, 38 organic acids, 28 phenylpropanoids, 17 alkaloids, 12 terpenoids, and 13 miscellaneous compounds. Network pharmacological analysis yielded 131 intersection targets converging on the PPAR, AMPK, HIF-1, and glucagon signaling pathways as principal effectors.
Conclusion
WDD acts as a multi-component orchestrator of lipid homeostasis through coordinated modulation of multiple pathways centered on PPAR signaling. These findings provide a molecular basis for the evidence-based application of WDD in hyperlipidemia management and establish a replicable analytical paradigm for TCM formula research.