Therapeutic role of d-pinitol on experimental colitis via activating Nrf2/ARE and PPAR-γ/NF-κB signaling pathways

Ulcerative colitis is a recrudescent intestinal inflammation coupled with diarrhea, weight loss, pus, and blood stool, which seriously impacts the quality of patient life. d-Pinitol, which can be a food supplement isolated from the food plant-like soybeans, Ceratonia siliqua Linn and Bruguiera gymnorrhiza, has been proved to show anti-oxidative and anti-inflammatory effects. However, the potential mechanism of d-pinitol still remains ill-defined contemporarily. In the current study, the therapeutic effect and potential mechanisms of d-pinitol against colitis were investigated. Oxidative stress and inflammation of experimental colitis were caused by 3% DSS treatment once daily for 7 days. During DSS treatment, the mice of the positive drug group and three other groups were orally administered SASP or d-pinitol once daily. Clinical symptoms were analyzed, and macroscopic scores were calculated. The levels of oxidative and inflammatory cytokines were measured using assay kits and RT-PCR. Additionally, the protein expression of the Nrf2/ARE pathway and PPAR-gamma was measured by Western blot. Results showed that d-pinitol enormously alleviated DSS-induced bodyweight loss, colon shortening, and histological injuries, achieving a therapeutic efficacy superior to SASP. Moreover, the oxidative stress and colonic inflammatory response were mitigated. d-pinitol not only significantly activated the Nrf2/ARE signaling pathway via facilitating the translocation of Nrf2 from sitoplazma to cytoblast, upregulating the protein expression levels of GCLC, GCLM, HO-1, and NQO1, but also improved the PPAR-gamma level by binding to the active site of PPAR-gamma, when suppressing NF-kappa B p65 and I kappa B alpha phosphorylation. In conclusion, d-pinitol exhibited a dramatic anti-colitis efficacy by activating the Nrf2/ARE pathway and PPAR-gamma. Hence, d-pinitol may be a promising therapeutic drug against UC in the future.

Automated summary

The study found that d-pinitol showed a superior therapeutic effect for ulcerative colitis compared to traditional drugs by alleviating oxidative stress and colonic inflammatory response through activation of the Nrf2/ARE signaling pathway and PPAR-gamma.