Ink melanin from Sepiapharaonis ameliorates colitis in mice via reducing oxidative stress, andprotecting the intestinal mucosal barrier

Melanin is the major component from Sepiapharaonis ink (MSI), and its anti-inflammatory and antioxidant activities indicate the potential for improvement of inflammatory bowel diseases. The study aimed to investigate how orally-administered MSI on alleviating the dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) and the potential mechanisms. We found that MSI significantly improved DSS-induced weight loss, colon shortening, hematochezia, DAI score, histopathology, and antioxidant indices (SOD and MDA). Further analysis demonstrated that MSI could significantly down-regulate the expression of pro-inflammatory cytokines (TNF-α, IL-1β and IFN-γ) and up-regulate the concentration of anti-inflammatory cytokine IL-10 by regulating TLR4/NF-κB and NLRP3/ASC/Caspase-1 signal pathway. Moreover, tight junction proteins in melanin groups were also maintained by ZO-1 and occludin expressions. In addition, MSI also regulated cellular apoptosis by reducing the expression of pro-apoptosis protein Caspase-3. Interestingly, MSI treatments increased the proportion of dominant bacteria (such as Bacteroidetes and Clostridium) and the abundance of community (alpha diversity, β-diversity, etc.), which significantly balanced microbiota in a dose-dependent manner. In conclusion, oral administration of MSI alleviated DSS-induced colitis by modulating inflammatory cytokines and oxidation stress, maintaining the mucosal barrier, and reverting microbiota changes.