Study on the mechanism of Gao-Liang-Huo decoction against dextran sulfate sodium-induced ulcerative colitis based on metabolomics and network pharmacology

• Published in: Pharmacological research. Modern Chinese medicine 2023-12, Vol.9, p.100304, Article 100304
• Main Authors: Tian, Qiang, Hu, Pei, Wang, Miaohua, Hu, Yu, Xie, Like, Li, Zhixiong, Xu, Zhou, Liu, Fang, Huang, Chenggang
• Format: Article
• Language: English
• Subjects: Gao-Liang-Huo decoction; Metabolomics; Molecular mechanism; Network pharmacology; Ulcerative colitis
• ISSN: 2667-1425; 2667-1425
• DOI: 10.1016/j.prmcm.2023.100304

•An integrated approach of metabolomics and network pharmacology was employed to investigate the potential mechanisms of GLH treatment for DSS-induced UC.•GLH significantly regulated 15 metabolites, which were enriched in tryptophan metabolism, glycerophospholipid metabolism, and citrate cycle (TCA cycle).•PIK3CA, PIK3R1, JAK1, JAK2, and JAK3 were identified as key targets, which mainly involved in the PI3K-AKT, JAK-STAT, and T-cell receptor signaling pathways.•GLH could regulate the PI3K-AKT pathway with decreased the expression levels of p-PI3KCA and p-AKT in DSS-induced UC Gao-Liang-Huo decoction (GLH), a traditional Chinese medicine consisting of gao liangjiang (the roots or tubers of Alpinia offinarum Hance) and guang huoxiang (the aerial parts of Pogostemon cablin (Blanco) Benth.), has been shown an effective therapeutic efficacy for ulcerative colitis (UC). However, the active compounds and underlying mechanisms involved in GLH treatment of UC remains unclear. This study aims to investigate the pharmacological mechanism of GLH on UC using an integrated strategy of metabolomics and network pharmacology. The experimental mice UC model was induced using dextran sulfate sodium (DSS). The disease activity index (DAI), colonic mucosa damage index (CMDI), biochemical assays, and histopathological analysis were used to evaluate the pharmacological effect of GLH. The LC/MS-based metabolomics was used for investigation of serum metabolites and metabolic pathways regulated by GLH. The potential targets and pathways of the active compounds in GLH were further explored using network pharmacology. Finally, the underlying mechanism of GLH on UC was verified by molecular docking and immunohistochemistry (IHC). The pharmacological experiments showed that GLH significantly ameliorated the DAI, CMDI, MDA, MPO, and histopathological changes in DSS-induced UC. The 15 metabolites were identified by metabolomics, such as L-tryptophan, taurocholic acid, glycocholic acid, 3-indolebutyric acid, and tryptophol. These metabolites were found to be enriched in tryptophan metabolism, glycerophospholipid metabolism, and citrate cycle (TCA cycle). The results of network pharmacology revealed the key targets, such as PIK3CA, PIK3R1, JAK1, JAK2, and JAK3, mainly involved in the PI3K-AKT, JAK-STAT, and T-cell receptor signaling pathways. Molecular docking showed high affinity interaction of quercetin, isorhamnrtin, poriferast-5-en-3beta-ol, 1,7-diphenyl-5-hydroxy-3-heptanone, and medi