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Paeonol alleviates ulcerative colitis by modulating PPAR-γ and nuclear factor-κB activation.

ABSTRACT: Ulcerative colitis (UC) is a chronic idiopathic inflammatory disease affecting the gastrointestinal tract. Although paeonol has been used for treating UC due to its anti-inflammatory and antioxidant effects, the underlying mechanisms remain unclear. In this study, we investigated the mechanisms of paeonol's action on UC by conducting in-vitro and in-vivo studies using NCM460 cells and RAW264.7 cells, and the DSS-induced mice colitis model. The in vitro studies demonstrate that paeonol exerts inhibitory effects on the activation of the NF-κB signaling pathway through upregulating PPARγ expression, thereby attenuating pro-inflammatory cytokine production, reducing reactive oxygen species levels, and promoting M2 macrophage polarization. These effects are significantly abrogated upon addition of the PPARγ inhibitor GW9662. Moreover, UC mice treated with paeonol showed increased PPARγ expression, which reduced inflammation and apoptosis to maintain intestinal epithelial barrier integrity. In conclusion, our findings suggest that paeonol inhibits the NF-κB signaling pathway by activating PPARγ, reducing inflammation and oxidative stress and improving Dss-induced colitis. This study provides a new insight into the mechanism of treating UC by paeonol.

SUBMITTER: Cheng S

PROVIDER: S-EPMC11310503 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Paeonol alleviates ulcerative colitis by modulating PPAR-γ and nuclear factor-κB activation.

Cheng Shuyu S Chen Wujin W Guo Zhenzhen Z Ding Chenchun C Zuo Renjie R Liao Quan Q Liu Guoyan G

Scientific reports 20240808 1

Ulcerative colitis (UC) is a chronic idiopathic inflammatory disease affecting the gastrointestinal tract. Although paeonol has been used for treating UC due to its anti-inflammatory and antioxidant effects, the underlying mechanisms remain unclear. In this study, we investigated the mechanisms of paeonol's action on UC by conducting in-vitro and in-vivo studies using NCM460 cells and RAW264.7 cells, and the DSS-induced mice colitis model. The in vitro studies demonstrate that paeonol exerts inh ...[more]

PMID: 39117680

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Project description:Background/objectivesUlcerative colitis (UC) is a chronic and easily recurrent inflammatory bowel disease. The gut microbiota and plasma metabolites play pivotal roles in the development and progression of UC. Therefore, therapeutic strategies targeting the intestinal flora or plasma metabolites offer promising avenues for the treatment of UC. Luteolin (Lut), originating from a variety of vegetables and fruits, has attracted attention for its potent anti-inflammatory properties and potential to modulate intestinal flora.MethodsThe therapeutic efficacy of Lut was evaluated in an established dextran sodium sulfate (DSS)-induced colitis mice model. The clinical symptoms were analyzed, and biological samples were collected for microscopic examination and the evaluation of the epithelial barrier function, microbiome, and metabolomics.ResultsThe findings revealed that Lut administration at a dose of 25 mg/kg significantly ameliorated systemic UC symptoms in mice, effectively reduced the systemic inflammatory response, and significantly repaired colonic barrier function. Furthermore, Lut supplementation mitigated gut microbiota dysbiosis in a UC murine model, increasing the abundance of Muribaculaceae, Rikenella, and Prevotellaceae while decreasing Escherichia_Shigella and Bacteroides levels. These alterations in gut microbiota also influenced plasma metabolism, significantly increasing phosphatidylcholine (PC), 6'-Deamino- 6'-hydroxyneomycin C, and gamma-L-glutamyl-butyrosine B levels and decreasing Motapizone and Arachidoyl-Ethanolamide (AEA) levels.ConclusionsThis study reveals that Lut supplementation modulates intestinal inflammation by restoring the gut microbiota community structure, thereby altering the synthesis of inflammation-related metabolites. Lut is a potential nutritional supplement with anti-inflammatory properties and offers a novel alternative for UC intervention and mitigation. In addition, further studies are needed to ascertain whether specific microbial communities or metabolites can mediate the recovery from UC.

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Dataset Information

Paeonol alleviates ulcerative colitis by modulating PPAR-γ and nuclear factor-κB activation.

Publications

Paeonol alleviates ulcerative colitis by modulating PPAR-γ and nuclear factor-κB activation.

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