Mechanism and Active ingredients of Gancao Qinlian Granules in ameliorating ulcerative colitis:integrated in vivo, in vitro, network pharmacology and untargeted metabolomics investigation.

Authors

Guangqin Liao, Maixun Zhu, Yang Zhang, Shaoqin Zhai, Chunlin Chen, Zhiqiang Yan, Lizhi Fu, Lanyan Zheng, Chao Song, Yuandi Yu, Hongmei Tang

Published in

Journal of ethnopharmacology. Pages 122263. Aug 01, 2026. Epub Aug 01, 2026.

Abstract

Gancao Qinlian Granules (GQG) are a granulated formulation of the classical prescription Gancao Xiexin Tang, originally documented by Zhang Zhongjing in the Treatise on Febrile and Miscellaneous Diseases (Shang Han Za Bing Lun, c. 220 CE). This formula comprises six medicinal components: Glycyrrhiza glabra L. (Gancao), the radix of Scutellaria baicalensis Georgi (Huangqin), Ziziphus jujuba Mill. (Dazao), the rhizomes of Zingiber officinale Roscoe (Ganjiang), the dried tuber of Pinellia ternata (Thunb.) Breit (Banxia) , and the rhizoma of Coptis chinensis Franch (Huanglian). GQG has been extensively employed in traditional and contemporary clinical practice for the treatment of ulcerative colitis (UC). Nevertheless, its candidate bioactive constituents and underlying mechanisms of action remain incompletely elucidated.
To comprehensively characterize the chemical composition of GQG and elucidate its therapeutic mechanisms against UC through an integrated strategy combining network pharmacology prediction, serum/colon/fecal multi-omics profiling (metabolomics and microbiome), and experimental validation.
Initially, GQG was analyzed by UHPLC-Q-Exactive Orbitrap MS under negative/positive ion modes, with compound identification via mzCloud, HMDB, and literature matching. C57BL/6 mice (n=8/group) were induced with UC using 3% dextran sulfate sodium (DSS) for 15 days. UC-related targets from GeneCard, PharmGkb, TTD, and OMIM were integrated to construct compound-target-pathway networks (Cytoscape 3.10.1). Secondly, GQG (9g/kg/d, 12g/kg/d, 15g/kg/d) or mesalazine (300 mg/kg) was administered orally for 10 days. Disease severity was assessed daily via Disease Activity Index (DAI: weight loss, stool consistency, bleeding). Post-euthanasia, colon length was measured, and histopathology (H&E, Alcian Blue-Periodic Acid Schiff staining) analyzed mucosal damage and goblet cell depletion. Colon IL-1β levels were quantified by immunohistochemistry (IHC). Then, serum, fecal, and colonic tissue samples underwent UHPLC-Q-Exactive Orbitrap MS-based untargeted metabolomics. Differentially expressed metabolites (DEMs) were identified (VIP >1, p<0.05) and pathways enriched via KEGG. Fecal 16S rDNA sequencing (Illumina NovaSeq) analyzed microbial α/β-diversity and differential taxa (LEfSe, LDA score >3). Subsequently, Integrated component analysis, network pharmacology, and metabolomics data to obtain the mechanism by which GQG improves UC, and verify the related target proteins through IHC and Western blot. Finally, obtain the candidate bioactive constituents in GQG through molecular docking, and verify the efficacy of these bioactive constituents with their targets on a cellular model.
Chemical profiling revealed 121 constituents in GQG, with 53 flavonoids (43.8%) including core bioactive markers (e.g., licoflavone B, licuroside). In DSS-induced ulcerative colitis mice, GQG (12g/kg/d) exerted potent therapeutic effects: reducing disease activity index, attenuating colon shortening, restoring goblet cells, and suppressing colon IL-1β. Mechanistically, GQG remodeled gut microbiota composition and function, increasing beneficial taxa (Muribaculaceae, Lactobacillus). This microbiota restructuring directly drove metabolic reprogramming. Suppression of pro-inflammatory metabolism: purine degradation (hypoxanthine), tryptophan-derived uremic toxins (kynurenine), pathogenic bile acids (deoxycholic acid). Integrative analysis of the microbiota-metabolite axis reveals that GQG extract can regulate the NF-κB/NLRP3 inflammasome cascade through p-NF-κB p65 expression, NLRP3 assembly (NLRP3, Caspase-1), and ASC speck formation. Combined with molecular docking, six key components in GQG exhibit high affinity for critical targets. In vitro cellular experiments demonstrate that these core candidate bioactive components effectively inhibit key targets within the target pathway.
GQG ameliorates UC by modulating gut microbiota structure and function, restoring microbial co-metabolism (e.g., SCFA synthesis, bile acid homeostasis), and subsequently inhibiting the NF-κB/NLRP3 inflammasome axis. This integrated approach substantiates the ethnopharmacological application of GQG for UC.

PMID:
42542265
Bibliographic data and abstract were imported from PubMed on 02 Aug 2026.

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