Dihydromyricetin ameliorates Salmonella enteritidis-induced pyroptosis and intestinal damage in chickens via modulating NLRP3 inflammasome.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Vine tea, as a non-camellia tea and ethnic medicine in China, exhibits an array of pharmacological effects. It exerts the effect of clearing heat and removing toxins, used to treat acute gastroenteritis, gastric ulcer, fever and hepatitis widely. Dihydromyricetin (DHM), abundant in vine tea, have been identified to have anti-inflammatory effect and antioxidant activity. Our prior research demonstrated that DHM mitigated intestinal damage induced by LPS in chickens. However, its potential mechanisms of action in Salmonella enteritidis (SE)-induced intestinal injury remain unclear. AIM OF THE STUDY: To investigate whether DHM ameliorate intestinal function and cellular damage in chicken challenged by SE and further elucidate potential mechanisms. MATERIALS AND METHODS: The metabolomics approach was applied to explore the specific metabolites and metabolic pathways. Subsequently, network pharmacology was employed to predict the potential regulatory pathways of DHM against salmonella enteritis. Meanwhile, it was validated using Hy-Line white-feathered broiler and HD11 cells. RESULTS: DHM significantly alleviated SE-induced intestinal pathological damage and serum metabolic disorders, reduced levels of pyroptosis-related factors LDH, IL-18 and IL-1β in chickens. Moreover, Network pharmacology analysis demonstrated that DHM might delay salmonella enteritis via pyroptosis by modulating inflammatory response and NOD-like receptor signaling pathway, with the NLRP3 inflammasome as a key target. Additionally, DHM reduced ROS levels and mitigated damage to cellular ultrastructure in SE-infected cells. Furthermore, DHM inhibited the activation of the NLRP3 inflammasome, thereby reducing the activation of caspase-1 and the expression of the pyroptosis effector protein GSDMA in vivo and in vitro. CONCLUSIONS: DHM could ameliorate chicken serum metabolic disorders and inhibit pyroptosis and intestinal damage, possibly via modulating NLRP3 inflammasome.