Efficacy evaluation and mechanism exploration of Dachaihu Decoction in treating hyperlipidemia: an integrated network meta-analysis and network pharmacology study.

BACKGROUND

Dachaihu Decoction (DCHD), a traditional herbal formula from Shanghan Lun, has been widely used in the management of hyperlipidemia. However, the comparative efficacy of its modified formulations and their underlying mechanisms remain unclear. This study aimed to evaluate the therapeutic efficacy of DCHD and its modifications and to elucidate the potential mechanisms using integrated analytical strategies.

METHODS

We conducted a Bayesian network meta-analysis (NMA) of randomized controlled trials (RCTs) systematically retrieved from multiple databases up to May 2024, following the PRISMA-NMA Guidelines. Lipid parameters, including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), as well as response rates, were evaluated. In addition, network pharmacology, molecular docking, and molecular dynamics (MD) simulations were performed to further explore the underlying mechanisms.

RESULTS

A total of 23 randomized controlled trials (RCTs) involving 1,816 patients were included. The surface under the cumulative ranking curve (SUCRA) analysis indicated that Dachaihu Decoction combined with Shengjiang Powder had the highest efficacy in reducing TC, TG, and LDL-C in patients with hyperlipidemic pancreatitis. However, sensitivity analysis revealed that Dachaihu Decoction alone and in combination with Guizhi Fuling Pill showed more stable efficacy in chronic populations. Network pharmacology identified 69 active components, including quercetin, β-sitosterol, and baicalein, and 305 intersecting targets. Protein-protein interaction (PPI) analysis highlighted TLR4, MMP9, SIRT1, ICAM1, and GSK3B as core targets. KEGG pathway enrichment analysis indicated significant involvement in lipid metabolism and inflammatory pathways. Molecular docking and molecular dynamics simulations revealed that the β-sitosterol-ICAM1 complex exhibited stable conformational stability, with an MM-GBSA binding free energy of -37.09 kcal/mol.

CONCLUSIONS

Modified DCHD formulations showed therapeutic potential for hyperlipidemia through multi-target and multi-pathway synergistic mechanisms. DCHD combined with Shengjiang Powder appears particularly promising in hyperlipidemic pancreatitis, whereas DCHD alone shows stable efficacy in chronic populations. These findings provide robust evidence supporting the rational clinical application and modern pharmacological interpretation of the classical formula DCHD documented in Shanghan Lun.