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.