Corosolic acid alleviates NAFLD mice reduced by high-fat diet by regulating cGAS-STING pathway via the microbiota-gut-liver axis

Corosolic acid (CRA) is a bioactive compound commonly utilized as a functional ingredient in health food formulations. However, its effects on the pathophysiology of non-alcoholic fatty liver disease (NAFLD) and the associated gut microbiota have remained largely uninvestigated. The study demonstrated that CRA administration reduced fat accumulation, attenuated body weight gain, and normalized serum lipid levels in NAFLD mice in a dose-dependent manner. Mechanistically, CRA appeared to modulate the gut-liver axis by enriching the growth of beneficial, short-chain fatty acids (SCFAs)-producing beneficial gut microbiota (e.g., Bacteroides, Prevotellaceae_UCG-001) while concurrently suppressing harmful bacteria implicated in liver pathology (Lachnoclostridium, Ileibacterium, Colidextribacter). Additionally, CRA enhanced the production of SCFAs in both gut contents and liver tissue. Transcriptomic analysis further elucidated CRA’s anti-inflammatory role, revealing its capacity to suppress inflammation by regulating pyroptosis and downregulating IL-1β expression. Moreover, these anti-inflammatory effects were attributed to the modulation of the cGAS-STING pathway and subsequent reduction in NLRP3 and IL-1β expression, ultimately leading to alleviation of liver inflammation. Collectively, these findings highlight CRA’s potential as a dietary supplement for NAFLD prevention and management.