Anti-inflammatory effects of anemonin on acute ulcerative colitis via targeted regulation of protein kinase C-θ

Background: Ulcerative colitis (UC) is an inflammatory bowel disease that causes continuous mucosal inflammation. Anemonin is a natural molecule from the Ranunculaceae and Gramineae plants that exerts anti-inflammatory properties. This study aimed to explore the effects and mechanisms of anemonin on UC. Methods: C57BL/6 mice were administered dextran sulphate sodium (DSS; 3% [w/v]) to establish an animal model of UC. Mice were treated with an intraperitoneal injection of anemonin. Body weight and the disease activity index (DAI) were recorded. Haematoxylin and eosin staining, RT-qPCR, ELISA, and western blotting were performed to evaluate the histopathological changes and tissue inflammation. HT-29 cells were treated with lipopolysaccharide (LPS) and anemonin. Cell inflammation was evaluated using RT-qPCR and western blotting. The target proteins of anemonin were predicted using bioinformatics analysis and confirmed in vitro and in vivo. Results: Anemonin improved DSS-induced body weight loss, shortened colon length, increased DAI, and induced pathological changes in the colon tissue of mice. Anemonin inhibited DSS-induced colon tissue inflammation as the release of IL-1 beta, INF-alpha, and IL-6 was significantly suppressed. Additionally, anemonin attenuated LPS-induced cytokine production in HT-29 cells. PKC-theta was predicted as a target protein of anemonin. Anemonin did not affect PRKCQ gene transcription, but inhibited its translation. PRKCQ overexpression partially reversed the protective effects of anemonin on HT-29 cells. Adeno-associated virus delivery of the PRKCQ vector significantly reversed the protective effects of anemonin on the mouse colon. Conclusions: Anemonin has the potential to treat UC. The anti-inflammatory effects of anemonin may be mediated through targeting PKC-theta.

Automated summary

The study found that anemonin can improve body weight loss, shortened colon length, increased DAI, and induced pathological changes in the colon tissue of UC mice. Anemonin inhibits DSS-induced colon tissue inflammation and also attenuates LPS-induced cytokine production in HT-29 cells. The anti-inflammatory effects of anemonin may be mediated through targeting PKC-theta.