Swertianin Suppresses M1 Macrophage Polarization and Inflammation in Metabolic Dysfunction-Associated Fatty Liver Disease via PPARG Activation.

Background: Metabolic dysfunction-associated fatty liver disease (MASLD) is closely associated with immune dysregulation and macrophage-driven inflammation. The activation of PPARG plays a critical role in modulating macrophage polarization and lipid metabolism, suggesting its potential as a therapeutic target for MASLD. Methods: We used UPLC-Q/TOF-MS and network pharmacology to investigate the key components and targets of Swertia davidi Franch, focusing on Swertianin. In vitro experiments on macrophages were conducted to assess the modulation of M1 polarization, and a mouse model of MASLD was utilized to explore the therapeutic effects of Swertianin. Results: Swertianin activated PPARG, leading to significant inhibition of M1 macrophage polarization, a reduction in lipid accumulation, and decreased inflammatory marker levels both in vitro and in vivo. The treatment significantly improved liver pathology in mice, indicating its therapeutic potential for MASLD. Conclusions: Swertianin's activation of PPARG provides a novel mechanism for treating MASLD, targeting both macrophage polarization and inflammation.