Work

Clinical efficacy and multi-target mechanisms of liver-dispersing, bile-inducing, and heat-clearing TCM formulas in cholelithiasis: network meta-analysis, network pharmacology, and molecular docking study

Year: 2026

Type: review

Study designs: Systematic Review, Meta-Analysis

Abstract: Objective: Although liver-soothing, gallbladder-benefiting, and heat-clearing (SGLDQR) traditional Chinese medicine (TCM) formulas are widely used for cholelithiasis, their systematic efficacy and molecular mechanisms remain poorly understood. This study integrated network meta-analysis (NMA), data mining, network pharmacology, and molecular docking to evaluate the clinical efficacy and clarify the molecular mechanisms of SGLDQR TCM formulas against cholelithiasis. Methods: Randomized controlled trials (RCTs) up to December 2024 were retrieved from eight databases. Risk of bias was evaluated using Cochrane RoB 2.0. NMA was conducted using Stata (v14.0) and R (v4.4.3), with treatments ranked by the surface under the cumulative ranking curve (SUCRA) and evidence certainty evaluated via CINeMA. Prescription patterns were mined using the Apriori algorithm. SGLDQR-cholelithiasis common targets were identified across multiple databases, followed by hub target screening using degree centrality and maximal clique centrality (MCC) algorithms and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment. Finally, blind whole-protein molecular docking of the top three hub targets with active ingredients was performed using AutoDock Vina (v1.1.2) and verified via PLIP. Results: Thirteen RCTs involving 1,364 patients and 12 SGLDQR formulas were included. NMA revealed that herbal formulas outperformed conventional Western medicine. Self-prepared Danshi Decoction (ZNDST) ranked highest in improving total effective rate (SUCRA: 88.2%), the Shugan Lidan Qingre formula (SGLDQRF) demonstrated potential superiority in improving TCM syndrome scores (SUCRA: 85.7%), and Rongpai Danshi Capsules (RPDSJN) exhibited a modulatory effect in reducing serum AST (99.9%) and ALT (100.0%) levels. Adverse events were mild and self-limiting. CINeMA certainty of evidence was low to very low. Data mining indicated that these formulas were predominantly cold in nature, combined bitter, pungent, and sweet flavors, and mainly targeted the spleen, liver, and stomach meridians, focusing on clearing heat, draining dampness, soothing the liver, and promoting gallbladder function, driven by 8 core herbs. Network pharmacology identified active compounds such as quercetin, wogonin, paeoniflorin, and aloe-emodin, which acted on key targets including IL-6, IL-1β, and TNF-α, primarily enriched in inflammatory cascades and lipid-metabolism pathways. Molecular docking predicted favorable binding affinities between the key active compounds and core targets. Conclusion: functional assays are warranted for validation. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024598181.

Source: Frontiers in Medicine

DOI: 10.3389/fmed.2026.1944318

Authors: Lian Cai, Yueqiao Lyu, Peipei Li, Mingzhu Li

Institutions: Anhui University of Traditional Chinese Medicine, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine

Language: English

Topic: Traditional Chinese Medicine Clinical Research

Subfield: Complementary and alternative medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801