Abstract
BACKGROUND AND PURPOSE Diosmetin exhibits a series of therapeutic
efficacy but little is known of its effects on colitis. EXPERIMENTAL
APPROACH In this study, two mouse models of DSS (the concentration of
3% and 5%)-induced colitis and Caco2 and IEC-6 cells were employed.
The 16S amplicon sequencing was used to assess Gut microbiota changes by
diosmetin. Various physical signs of mice (body weight, colon length and
DAI score), proinflammatory cytokines and antioxidant enzymes were
tested. KEY RESULTS The results showed that diosmetin can markedly
decrease the disease activity index and microscopic colon tissue damage,
increase the expression of tight junction protein (Occludin, Claudin-1
and Zo-1) and reduce the secretion of proinflammatory cytokines. And
diosmetin also significantly inhibited colon oxidative damage through
adjusting the levels of intracellular ROS, mitochondrial ROS, GSH-Px,
SOD, MDA and GSH in vitro and in vivo. Furthermore, it was found that
diosmetin can modulate the abundance of Bacteroidetes, Actinobacteria,
Cyanobacteria and Firmicutes, which were reported to be the crucial
bacteria related to inflammatory bowel disease (IBD). CONCLUSIONS AND
IMPLICATIONS Our data suggested that diosmetin ameliorated the colitis
in mice induced by DSS in the potential mechanism that it alleviates
intestinal epithelial barrier damage, inhibits the secretion of
proinflammatory cytokines, decreases oxidative stress and modulates gut
microbiota. It implies that diosmetin may be a novel candidate to
alleviate DSS-induced colitis or a lead compound for future optimization
and modification.