Supplementary file 1_Artemisia scoparia extract inhibits oxidative stress and ferroptosis to ameliorate MASH through AGE-RAGE and JAK1-STAT3 signaling.docx

BackgroundMetabolic dysfunction-associated steatohepatitis (MASH) is the most prevalent chronic liver disease worldwide; however, few effective therapeutic options are available for MASH. Artemisia scoparia is a medicinal plant that has been widely utilized in traditional medicine to treat liver-related ailments. Nonetheless, the effects and underlying mechanisms of A. scoparia in the context of MASH remain poorly understood.
Aim of the studyThe objective of this research was to assess the protective effects and further mechanisms of A. scoparia extract (AS) on a MASH mice model.
MethodsThe protective effects of AS were evaluated both in vivo and in vitro, with the therapeutic efficacy of AS being characterized through the detection of biochemical markers, histological analysis, and Oil red O staining. To elucidate the underlying mechanisms and pharmacodynamic basis of AS, a comprehensive set of techniques were applied, including transcriptomics, metabolomics, Western blotting, and immunofluorescence staining.
ResultsAS reduced the blood lipid indices and inflammatory levels in the MASH mouse model and decreased lipid droplet accumulation in FFA-induced HepG2 cells. Transcriptomic and metabolomic analyses indicated that AS regulates 30 dysregulated genes (e.g., Gm15622, Pdia6, and Derl3) and controls 60 metabolic metabolites (e.g., heptadecanoic acid, 5b-cyprinol sulfate, and taurodeoxycholic acid) to ultimately affect core pathways involved in lipid metabolism and inflammation. Furthermore, AS was proven to exert a hepatoprotective effect by inhibiting inflammation and ferroptosis, along with weakening the advanced glycation end product–receptor for advanced glycation end products (AGE–RAGE) pathway and the Janus kinase–signal transducer and activator of transcription (JAK–STAT) pathway in vivo and in vitro.
ConclusionThis study first elucidates the mechanism through which AS ameliorates MASH through integrated multi-omics analysis, providing experimental evidence for further development of natural therapeutic agents.