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. 2024 Aug;32(4):2589-2599.
doi: 10.1007/s10787-024-01493-0. Epub 2024 May 20.

Aegeline attenuates TNBS-induced colitis by suppressing the NFƙB-mediated NLRP3 inflammasome pathway in mice

Bhagyabhumi Shah  1 , Nilay Solanki  2
Affiliations

Aegeline attenuates TNBS-induced colitis by suppressing the NFƙB-mediated NLRP3 inflammasome pathway in mice

Bhagyabhumi Shah et al. Inflammopharmacology. 2024 Aug.

Abstract

A chronic inflammatory condition of the intestine, ulcerative colitis (UC), is challenging to successfully manage once diagnosed. Currently, available medical therapies for UC exhibit minimal efficacy with unacceptable side effects, while inventive biological agents are expensive and yet not well accepted by patients. Discovering more effective and safer treatments to treat UC is therefore essential. One of the primary alkaloids found in Aegle marmelos, aegeline, has anti-inflammatory and antioxidant properties as well as being able to suppress several pro-inflammatory cytokines responsible for inflammation. The study aimed to investigate the effectiveness of aegeline in alleviating 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis through the NFƙB-mediated NLRP3 inflammasome pathway. Mice were randomly allocated into six groups, Normal control (NC), Model control (MC-TNBS, 2,4,6-trinitrobenzene sulfonic acid), STD (TNBS + sulfasalazine 100 mg/kg), AG1, AG2, and AG3 (TNBS + aegeline 5, 10, 20 mg/kg) respectively. Physical parameters such as a change in body weight, stool consistency, rectal bleeding, colon length, myeloperoxidase (MPO) levels and nitric oxide (NO) levels, and disease activity index (DAI) were assessed and supporting gene expression studies of various pro-inflammatory cytokines and enzymes were evaluated and histopathological changes observed. Administration of aegeline (10, 20 mg/kg) was found to be effective in colon protection by lowering the disease activity score and myeloperoxidase level and improving other physical parameters. Aegeline in high dose significantly downregulated the gene expression of NFƙB, iNOS, COX-2, NLRP3, IL-1β, and IL-18, conferring great anti-inflammatory potential. Suggestive of the findings, aegeline reduced the damage to the colon by downregulating transcriptional genes and enzymes leading to inflammation and mitigated TNBS-induced colitis probably through the NFƙB-mediated NLRP3 inflammasome pathway.

Keywords: Aegeline; Inflammatory bowel disease; NFƙB pathway; NLRP3 inflammasome; Ulcerative colitis.

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