Deciphering the multi-target mechanisms of TCM formulas in hyperlipidemia treatment through meta-multi-omics data and UK Biobank analysis
European Journal of Integrative Medicine, 2026
Chang X., Qiu J., Wang Z., Wu Z., Feng Y., Cheong K., Yu L., Jiang Y., Huang C.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Metabolic Diseases | Pathophysiology | Plasma |  Olink Explore 3072/384 |
Abstract
ntroduction
Traditional Chinese Medicine (TCM) effectively treats hyperlipidemia through distinct syndromes; however, formula selection often lacks a scientific rationale. We integrated network pharmacology, Mendelian randomization (MR), RNA sequencing (RNA-seq) analysis, proteomics and observational analyses using the UK Biobank to elucidate the mechanisms of four TCM formulas (Wendan Decoction, Weiling Decoction, Xuefu Zhuyu Decoction, Yiguan Decoction and Qijudihuang Pill) in hyperlipidemia.
Methods
Network pharmacology analysis identified bioactive compounds and targets from TCM databases; MR integrated blood-derived eQTL/meQTL/pQTL with hyperlipidemia GWAS to infer important targets; bulk RNA-seq and single-cell RNA sequencing (scRNA-seq) validated cell-type-specific target expression and immune interactions in hyperlipidemic tissues; the UK Biobank cohort provided clinical validation of MR-derived targets.
Results
Network analysis classified formulas into three functional clusters based on shared symptoms, compounds, and targets. MR analysis revealed 13 key mechanisms-of-action (MOA) targets across three functional clusters (e.g., GSTM2 and IGF1R for anti-inflammatory and antioxidant effects; TYK2 and LGALS4 for immune regulation and cell adhesion; PCSK7 and APOB for lipid metabolism). Literature screening combined with scRNA-seq analysis linked most MOA-related targets to specific formulas and symptoms. Analysis of UK Biobank plasma protein data identified significant differences in important targets between patient and control groups, with Cox regression models revealing associations between specific plasma proteins and hyperlipidemia.
Conclusion
This study establishes an integrative multi-omics framework for TCM research, by which we could bridge empirical TCM syndromes with molecular mechanisms, providing a translatable framework for evidence-based TCM formula development, directly informing clinical practice.