Metabolomics combined with network pharmacology revealed a paradigm for determining the mechanism underlying the metabolic action of Gegen Qinlian Decoction amelioration of ulcerative colitis in mice.

Autor: Zhang M; School of Basic Medical Sciences, Guizhou Medical University, Guiyang 550004, China; Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang 550004, China; Natural Products Research Center of Guizhou Province, Guiyang 550014, China; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China., Jin Y; Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang 550004, China., Wu T; School of Basic Medical Sciences, Guizhou Medical University, Guiyang 550004, China; Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang 550004, China., Zhao Q; Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang 550004, China; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550004, China., Li H; Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang 550004, China; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550004, China., Zhang H; Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang 550004, China; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550004, China., Lu Y; Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang 550004, China., Chen S; Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang 550004, China., Liu T; Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang 550004, China., Gong Z; Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang 550004, China., Wang D; Natural Products Research Center of Guizhou Province, Guiyang 550014, China; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China., Liu W; School of Basic Medical Sciences, Guizhou Medical University, Guiyang 550004, China; Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang 550004, China; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550004, China. Electronic address: liuwen@gmc.edu.cn.
Jazyk: angličtina
Zdroj: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences [J Chromatogr B Analyt Technol Biomed Life Sci] 2024 Nov 08; Vol. 1250, pp. 124352. Date of Electronic Publication: 2024 Nov 08.
DOI: 10.1016/j.jchromb.2024.124352
Abstrakt: Ulcerative colitis (UC) is a common disease of the digestive system that is challenging to treat. Gegen Qinlian Decoction (GQD), which is an ancient classic formula in Chinese medicine, is effective at alleviating the symptoms of UC, but comprehensive research on its mechanism of action has not been performed. Here, we explored the material basis and potential molecular mechanism underlying GQD-mediated protection against UC by integrated metabolomics and network pharmacology. First, differentially expressed metabolites were screened and identified via a metabolomics approach, and the metabolic pathway was analyzed via MetaboAnalyst. Second, a protein-protein interaction (PPI) network was constructed to identify hub genes that encode metabolic enzymes. Third, the differentially expressed metabolites were used to construct a compound-reaction-enzyme-gene network. Finally, the metabolites were compared with relevant active components for molecular docking, molecular dynamics (MD) simulation, and verification experiment. GQD intervention alleviated UC in mice and significantly inhibited metabolic dysfunction in mice with UC; specifically, GQD reversed the abnormal changes in metabolites in the colon and serum, and regulated the arachidonic acid metabolism, tryptophan metabolism, glycerophospholipid metabolism, and purine metabolism pathways. Further literature review and molecular docking analysis with targeted MD simulation and Poisson-Boltzmann surface area (MM-PBSA) analysis were performed, revealing that GQD may inhibit the disruption of arachidonic acid metabolism and tryptophan metabolism by suppressing PTGS2 and CYP450 protein expression; these results were verified by qRT-PCR, WB, and surface plasmon resonance (SPR) assays. Our experiments indicated that GQD alleviated UC in mice by systematically regulating arachidonic acid metabolism and tryptophan metabolism, supporting further research and the development of GQD as a novel drug for ameliorating UC.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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