Journal of inflammation research · 2026
Network Pharmacology-Metabolomics Integration Reveals the Multiple Targets and Mechanisms of Total Glucosides of Paeony Against Ulcerative Colitis.
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Wang Yifei, Han Yuxin, Teng Fei, Liu Yi, Ma Liangjie, Ji Wenqi, Ma Xiao
Аннотация
OBJECTIVE: The total glucosides of paeony (TGP), extracted from the roots of Paeonia lactiflora Pall., represent its primary bioactive fraction. Emerging evidence supports its clinical potential in treating ulcerative colitis (UC). Nevertheless, a systematic understanding of its underlying pharmacological mechanisms remains insufficient. This study aims to comprehensively investigate the multi-target, multi-pathway therapeutic mechanisms of TGP against UC by employing an integrated strategy combining network pharmacology and untargeted metabolomics, with subsequent experimental validation.
METHODS: Induction of the colitis mouse model was performed by supplementing drinking water with dextran sulfate sodium (DSS), and an in vitro model was created by treating NCM460 intestinal epithelial cells with lipopolysaccharide. The DSS-induced colitis mice were orally administered low-, medium-, or high-dose TGP at 0.093, 0.185, or 0.369 g/kg/day, respectively, while LPS-stimulated NCM460 cells were treated with TGP at 100, 200, or 400 μg/mL. The therapeutic effects of TGP were assessed in vivo through the disease activity index (DAI), colon length measurement, and histopathological examination. Colon tissues were collected for subsequent non-targeted metabolomics analysis via liquid chromatography- tandem mass spectrometry (LC-MS/MS). The mechanisms underlying the effects of TGP were explored through integrated network pharmacology and metabolomics studies and further verified using RT-PCR, ELISA, Western blot, and flow cytometry.
RESULTS: TGP treatment significantly decreased DAI scores, reduced colon shortening, and ameliorated histopathological lesions in the DSS-induced colitis mouse model. Network pharmacology analysis revealed that the therapeutic effects of TGP on UC are primarily mediated through various inflammatory mediators and signaling pathways. Integrated metabolomics analysis further identified the COX-2-mediated arachidonic acid pathway as a key pathway. Both in vivo and in vitro, TGP dose-dependently reduced the expression of IL-6, TNF-α, and COX-2 and suppressed the activation of AKT, p38 MAPK, and NF-κB signaling. In DSS-treated mice, TGP-H reduced the splenic Th17/Treg ratio.
CONCLUSION: TGP exerts its therapeutic effects on UC through the inhibition of various inflammatory targets and signaling pathways.
METHODS: Induction of the colitis mouse model was performed by supplementing drinking water with dextran sulfate sodium (DSS), and an in vitro model was created by treating NCM460 intestinal epithelial cells with lipopolysaccharide. The DSS-induced colitis mice were orally administered low-, medium-, or high-dose TGP at 0.093, 0.185, or 0.369 g/kg/day, respectively, while LPS-stimulated NCM460 cells were treated with TGP at 100, 200, or 400 μg/mL. The therapeutic effects of TGP were assessed in vivo through the disease activity index (DAI), colon length measurement, and histopathological examination. Colon tissues were collected for subsequent non-targeted metabolomics analysis via liquid chromatography- tandem mass spectrometry (LC-MS/MS). The mechanisms underlying the effects of TGP were explored through integrated network pharmacology and metabolomics studies and further verified using RT-PCR, ELISA, Western blot, and flow cytometry.
RESULTS: TGP treatment significantly decreased DAI scores, reduced colon shortening, and ameliorated histopathological lesions in the DSS-induced colitis mouse model. Network pharmacology analysis revealed that the therapeutic effects of TGP on UC are primarily mediated through various inflammatory mediators and signaling pathways. Integrated metabolomics analysis further identified the COX-2-mediated arachidonic acid pathway as a key pathway. Both in vivo and in vitro, TGP dose-dependently reduced the expression of IL-6, TNF-α, and COX-2 and suppressed the activation of AKT, p38 MAPK, and NF-κB signaling. In DSS-treated mice, TGP-H reduced the splenic Th17/Treg ratio.
CONCLUSION: TGP exerts its therapeutic effects on UC through the inhibition of various inflammatory targets and signaling pathways.