Cobalt Metal-organic Framework Alleviates DSS-Induced Ulcerative Colitis Via Barrier-protective and Immunomodulatory Effects

Ulcerative colitis (UC) is characterized by excessive cytokine production, epithelial barrier disruption, and oxidative stress. It necessitates therapeutics with immunomodulation and mucosal integrity restoration. This study aimed to evaluate in-vivo and in-vitro therapeutic potential of Fe-MOF, Cr-MOF, and Co-MOF. RAW264.7 macrophages and DSS-induced murine colitis model were used. SEM, FTIR, XRD, and ICP-MS were used for characterization of MOFs. Cytotoxicity, immunofluorescence, ELISA, histopathology, immunoblotting, and qPCR analyses were used to evaluate effects of MOFs. Co-MOF showed a significant immunomodulatory effect by reducing LPS-induced TNF-α, IL-6, and IL-1β expression at both mRNA and protein levels in RAW264.7 macrophages. It also alleviated DSS-induced TNF-α, IL-6, and IL-1β levels in mouse colon, as indicated by ELISA and immunofluorescence. Co-MOF also reduced DAI score, improved body weight loss, and preserved colon length in the DSS-induced colitis model. Co-MOF also restored tight-junction proteins such as Occludin and ZO-1, significantly reduced by DSS in colon. Histopathological examination validated substantial protection of mucosal architecture, including intact crypts, restored goblet cell populations, and attenuated immune-cell infiltration. A notable antioxidant effect of Co-MOF was also observed, as it increases SOD and CAT activities while reducing MDA. Co-MOF significantly normalized platelets, lymphocytes, and neutrophils, elevated by DSS. Co-MOFs did not induce systemic toxicity and vital organ injury, predicting their biosafety. Conclusively, Co-MOF showed better immunomodulatory effects and barrier protection compared to Fe-MOF and Cr-MOF in UC, which further requires mechanistic validation.