Manumycin A Attenuates DSS-Induced Colitis in Mice via Anti-Inflammatory Effects Following Intraperitoneal Administration.

Background/

Objectives

Manumycin A, a natural polyketide antibiotic isolated from Streptomyces species, has been reported to exhibit anticancer, anti-inflammatory, and immunomodulatory activities through regulation of multiple signaling pathways. However, its therapeutic potential in inflammatory bowel disease (IBD) has not yet been investigated. This study aimed to evaluate the protective effects of Manumycin A in a dextran sulfate sodium (DSS)-induced colitis mouse model.

Methods

Experimental colitis was induced in male ICR mice by administration of 3% DSS in drinking water for 7 days. Manumycin A (1, 5, and 10 mg/kg) was administered via intraperitoneal injection, and 5-aminosalicylic acid (100 mg/kg) was used as a positive control. Disease severity was evaluated by body weight changes, disease activity index (DAI), colon length, histopathological analysis, and immunohistochemical assessment of pro-inflammatory cytokines, including IL-1β, IL-6, TNF-α, and IFN-γ.

Results

Manumycin A treatment attenuated DSS-induced colitis in a dose-dependent manner. Although body weight changes were modest and did not show statistically significant differences among groups, Manumycin A significantly reduced DAI scores compared with the DSS-treated group. Treatment also alleviated DSS-induced colon shortening and improved histopathological alterations, including epithelial damage, mucosal disruption, and inflammatory cell infiltration. Immunohistochemical analysis showed that Manumycin A reduced the expression of IL-1β, IL-6, TNF-α, and IFN-γ in colon tissues.

Conclusions

Manumycin A exerted protective effects against DSS-induced colitis by attenuating inflammatory responses and improving colonic tissue damage. These findings suggest that Manumycin A may have therapeutic potential as a candidate for the treatment of IBD.