Sinomenine attenuated dextran sulfate sodium-induced inflammatory responses by promoting 14-3-3θ protein and inhibiting NF-κB signaling

Abstract

Ethnopharmacological relevance: The rhizome of Chinese medical plant QingTeng (scientific name: Sinomenium acutum (Thunb.) Rehd. et Wils.) is widely used by traditional medical doctors for anti-inflammation and immunoregulatory in China and other Asian countries.

Aim of the study: The purpose of this study was to evaluate the effects and possible mechanisms of sinomenine resistance against DSS-induced inflammation in vitro and in vivo.

Materials and methods: The UC model was induced by treating female mice with 3% DSS in vivo and human colonic epithelial cells (Hcoepic) with 0.8 mg/ml DSS in vitro. The mice and Hcoepic were then treated with sinomenine. Inflammatory factors were detected using ELISA and qRT-PCR. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 and 14-3-3θ were analyzed by bioinformatic analysis and verified by western blotting, immunofluorescent staining or immunohistochemistry.

Results: DSS-induced Hcoepic underwent high inflammation and oxidative stress conditions, whereas sinomenine reduced the uncontrolled immune microenvironment by suppressing NF-κB signaling and targeting 14-3-3θ. Knockdown of 14-3-3θ decreased the protective effect of sinomenine against DSS-induced inflammation in vitro. Moreover, sinomenine promoted 14-3-3θ protein expression and inhibited NF-κB p65 signaling in DSS-induced mice.

Conclusion: These findings suggest that 14-3-3θ plays an important role in sinomenine against DSS treatment, and sinomenine could be considered a potential drug for the treatment of UC.

Keywords: 14-3-3θ; Inflammation; NF-κB; Sinomenine; Ulcerative colitis.