Muscone alleviated acetic acid-induced ulcerative colitis in mice through inhibiting NF-κB, IL-23/IL-17A axis, COX-2, and oxidative stress

Abstract Background Ulcerative colitis (UC) is an autoimmune condition distinguished by prolonged inflammation of the intestinal mucosa with fluctuating periods of relapse and remission. This research was designed to evaluate the prospective alleviative impacts of muscone (3-methyl-1-cyclopentadecanone) on inflammatory processes and oxidative stress in the acetic acid (AA)-provoked UC in mice. Methods The experimental colitis was provoked by intrarectal injection of 200 μL of AA (6% volume/volume with 0.9% sterile saline). Mice were intrarectally (I.R.) administered with sulfasalazine “SSZ” (500 mg/kg body weight “b.w”) or muscone (20 or 40 mg/kg b.w) in 200 μL sterile saline at one hour (h), 6 h, and 12 h following the I.R. administration of AA. A day after the induction of UC, animals were humanely executed, and their colons were harvested for morphological, histological, immunohistochemical, along with biochemical assays. Results Muscone ameliorated the colitis severity in mice, as signified by a considerable decline ( P < 0.05) in colon weight-to-length ratio, macroscopic damage, and histological alterations. Furthermore, muscone increased considerably the colonic levels of reduced glutathione (GSH) and the activities of superoxide dismutase (SOD) and catalase (CAT), while decreasing the levels of malondialdehyde (MDA) and nitric oxide (NOx) in UC mice. Muscone also lowered significantly the levels of colonic NF-κB and COX-2, in addition to inhibiting the production of IL-17A and IL-23 in the colons of UC mice. Conclusion Muscone could serve as an efficacious treatment for alleviating the inflammatory processes in UC mice, as it inhibits NF-κB, IL-23/IL-17A axis, COX-2, and enhances the antioxidant defense system in colon tissues.