Maslinic Acid Ameliorates DSS-Induced Experimental Colitis by Suppressing Th Cell-Mediated Inflammation via AICD Induction

马斯林酸通过诱导AICD抑制Th细胞介导的炎症,从而改善DSS诱导的实验性结肠炎。

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Abstract

Ulcerative colitis (UC) is a nonspecific chronic inflammatory disease that occurs in the gastrointestinal tract and is characterized by the breakdown of mucosal immunity. T helper (Th) cells paradigm disequilibrium is a critical for pathogenesis. Maslinic acid (MA), a naturally occurring pentacyclic triterpene isolated from olive pomace and Fructus crataegi, has a variety of applications in both medicine and food. This study investigated the molecular mechanism of the anti-inflammatory potential of MA in a colitis model and activated Th cells. A dextran sulfate sodium-induced experimental colitis model was established. Clinical symptoms were evaluated, and biological samples were collected to examine intestinal mucosal function, inflammation levels, and Th cell-mediated immune responses. The mechanism of the activation-induced cell death (AICD) effect regulated by MA was investigated in the anti-CD3ε/CD28-stimulated Th cell activation model using molecular biotechnology and transcriptome analysis. Key results:MA treatment protected intestinal mucosa, which manifested as reduced inflammatory cytokines, Th cell infiltration, and subset differentiation. Additionally, it was found to suppress Th cell proliferation and differentiation of subsets, regulate cell cycle distribution, and promote AICD by regulating the mitochondria-mediated intrinsic pathway in vitro. JAK-STAT and FcεRI pathways were probable essential pathways, and MAF might be a crucial potential targeting molecule in activated Th cells with MA treatment. This finding demonstrated that MA induced remission of the colitis-related inflammation, which may depend on the resolution of acute inflammation by reducing Th cell-mediated inflammation via AICD induction, emphasizing its promising potential in the treatment of UC.

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