Mechanistic Exploration of Wendan Decoction in Hyperlipidemia Treatment: An Integrated Network Pharmacology and Metabolomics Analysis
Abstract
Objective 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. In vivo , WDD significantly reduced plasma TC, TG, and LDL-C while dose-dependently elevating HDL-C in hyperlipidemic rats ( P < 0.05), accompanied by marked attenuation of hepatic steatosis. Plasma metabolomics identified 60 common differential metabolites—predominantly glycerophospholipids and sphingolipids—enriched across seven KEGG pathways including glycerophospholipid metabolism, linoleic acid metabolism, and bile secretion. Cross-platform integration revealed the PPAR signaling pathway as the mechanistic nexus connecting network pharmacology-derived targets and metabolome-level perturbations. 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.
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BibTeX
@article{xu2026mechanistic,
title = {{Mechanistic Exploration of Wendan Decoction in Hyperlipidemia Treatment: An Integrated Network Pharmacology and Metabolomics Analysis}},
author = {Nan Xu and Jing-wen Ma and Xiao-xue Yin and Ya-nan Xiao and Xin-gang Xu and Lei Ma and Muhammad ljaz and Hai-yan Shi},
journal = {Natural Product Communications},
year = {2026},
month = oct,
doi = {10.1177/1934578x261501922},
url = {https://doi.org/10.1177/1934578x261501922},
note = {CC BY},
}
RIS
TY - JOUR
TI - Mechanistic Exploration of Wendan Decoction in Hyperlipidemia Treatment: An Integrated Network Pharmacology and Metabolomics Analysis
AU - Nan Xu
AU - Jing-wen Ma
AU - Xiao-xue Yin
AU - Ya-nan Xiao
AU - Xin-gang Xu
AU - Lei Ma
AU - Muhammad ljaz
AU - Hai-yan Shi
PY - 2026
DA - 2026/10/27
JO - Natural Product Communications
DO - 10.1177/1934578x261501922
UR - https://doi.org/10.1177/1934578x261501922
AB - Objective 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. In vivo , WDD significantly reduced plasma TC, TG, and LDL-C while dose-dependently elevating HDL-C in hyperlipidemic rats ( P < 0.05), accompanied by marked attenuation of hepatic steatosis. Plasma metabolomics identified 60 common differential metabolites—predominantly glycerophospholipids and sphingolipids—enriched across seven KEGG pathways including glycerophospholipid metabolism, linoleic acid metabolism, and bile secretion. Cross-platform integration revealed the PPAR signaling pathway as the mechanistic nexus connecting network pharmacology-derived targets and metabolome-level perturbations. 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.
SN - 1555-9475
SN - 1934-578X
ER -