Introduction

Oxidative stress disruption are involved in the occurrence and development of inflammatory bowel disease(IBD). Previous reports have shown that melanin nanoparticles (MNPs) have the function of regulating oxidative stress. The aim of this study is to explore the preventive effect of MNPs on DSS-induced colitis in mice and its mechanism.

Aims & Methods

In this study, C57BL/6 wild-type mice were divided into 7 groups according to whether induced colitis by DSS, whether prophylactic application of MNPs or mesalazine, and different administration method. Mice were randomly assigned to control group, DSS group, MNPs gavage (MNPs-ig+DSS), MNPs enema (MNPs-en+DSS), MNPs enema + gavage (MNPs-bo+DSS), MSL gavage (MSL-ig+DSS), and MSL gavage + enema group (MSL-bo+DSS). The effect of MNPs on DSS-mice was evaluated by clinical manifestation, length of colon, pathological scores of colon tissues, and the level of inflammatory cytokines. The distribution and expression of intestinal mucosal junction proteins Occludin (OCC) and ZO-1 were detected to evaluate the effect of MNPs on colon mucosal barrier. In addition, the abundance and species distribution of intestinal microbiota were determined by 16S rRNA sequencing in each group. In the mechanism exploration part, the level of superoxide dismutase (SOD) and malondialdehyde (MDA) were used to evaluate the activity of reactive oxygen species (ROS) in mouse colon tissue, and the expression of ROS-related NLRP3/NF-κB signaling pathway-related proteins was further detected. In addition, this study verified the effect of MNPs on liver and kidney through the evaluation of organ morphology and function.

Results

C57BL/6 wild-type mice showed weight loss, colon shortening, increase of DAI and intestinal pathological scores, accompanied by increased levels of intestinal inflammatory cytokines TNF-α, IL-1β and IL-6 and decreased levels of IL-10 in colon tissue, which can be prevented by the application of MNPs to a certain extent. MNPs can help protected the integrity of the intestinal mucosal barrier, which is manifested by the restoration of the distribution and expression of tight junction proteins ZO-1 and Occludin. However, 16S rRNA sequencing failed to show a significant regulatory effect of MNPs on the intestinal microbiota. MNPs can significantly reduce the level of colonic SOD and increase the level of MDA induced by DSS, and this effect was related to the inhibition of the activation of NLRP3 inflammasome and the expression of downstream NF-κB inflammatory signaling pathway proteins. Finally, MNPs had no effect on the morphology and function of liver and kidney.

Conclusion

MNPs can improve colitis and regulate mucosal barrier function in mice, which may be related to reduced oxidative stress and inhibited activation of NLRP3 inflammasome and downstream NF-κB inflammatory signaling pathway. Our findings suggest the potential value of MNPs as a treatment for IBD.