Rhein Inhibits PI3K/Akt/mTOR Signaling Pathway to Show Efficacy in an Ulcerative Colitis Mice Model

Abstract

Dong and his associates investigated the potential therapeutic effect of Rhein on ulcerative colitis (UC) and its mechanism in mouse models of human disease. Their results showed a decrease in the levels of TNF-α, IL-6, IL-1β, and other cytokines responsible for promoting inflammation. Moreover, both in-vivo and in-vitro mitigation of UC-associated symptoms such as colon shortening, weight loss, diarrhea, and hematochezia stimulated by dextran sodium sulfate was seen. Through western blotting, decreasing phosphorylated protein levels of PI3K, Akt, mTOR, and p70S6K1 by Rhein was evident which indicates inhibition of the PI3K/Akt/mTOR signaling pathway. Rhein administration also partially reversed the gut dysbacteriosis of mice induced by dextran sulfate sodium. A decrease in pathogenic bacteria (e.g., Enterobacteriaceae and Turicibacter) as revealed by 16sRNA gene sequencing was also observed. The authors conclude that Rhein possesses anti-UC activity as exhibited by alleviating the signs and symptoms of UC and diminishing gastrointestinal inflammation by blocking the PI3K/Akt/mTOR signaling pathway and modulating stomach microbiota. Phytother Res. 2022 May;36(5):2081-2094.