Inflammatory bowel diseases (IBDs) constitute a group of chronic intestinal conditions prominently featuring deranged metabolism. Effective pharmacological treatments for IBDs are lacking.
Isosteviol sodium (STV-Na) exhibits anti-inflammatory activity and may offer therapeutic benefits in chronic
colitis. However, the associated mechanism remains unclear. This study is aimed at exploring the
therapeutic effects of STV-Na against chronic
colitis in terms of metabolic reprogramming and macrophage polarization. Results show that STV-Na attenuated
weight loss and colonic pathological damage and restored the hematological and biochemical parameters in chronic
colitis mice models. STV-Na also restored intestinal permeability by increasing the goblet cell numbers, which was accompanied by lowered plasma
lipopolysaccharide and
diamine oxidase levels. Metabolomic analysis highlighted 102 candidate
biomarkers and 5 vital pathways that may be crucial in the potential pharmacological mechanism of STV-Na in regulating intestinal
inflammation and oxidative stress. These pathways were
glycerophospholipid metabolism,
phenylalanine metabolism,
phenylalanine,
tyrosine and
tryptophan biosynthesis, the pentose phosphate pathway, and
phosphonate and phosphinate metabolism. Furthermore, STV-Na significantly decreased M1 macrophage polarization in the spleen and colon. The
mRNA and
protein levels of IL-1β, TNF-α, and NF-κB/p65 in colonic tissue from the
colitis mice were decreased after the STV-Na treatment. Overall, STV-Na could alleviate chronic
colitis by suppressing oxidative stress and
inflammation levels, reprogramming the metabolic profile, inhibiting macrophage polarization, and suppressing the NF-κB/p65 signaling pathway. STV-Na remains a promising candidate drug for treating IBDs.