(P04-018-24) Artemisia argyi Ameliorates Nonalcoholic Steatohepatitis by Modulating Fibrosis-Related Factors and Gut Microbiota

Objectives: The absence of effective pharmaceutical interventions for non-alcoholic steatohepatitis (NASH), a major contributor to fibrosis and end-stage liver disease, highlights the potential of medicinal plants in drug development. Artemisia argyi (AA), an herbal medicine originating from East Asia, shows diverse biological effects. This study aims to investigate the effects of AA ethanol extract and its active components on NASH-related fibrosis and gut microbiota in a mouse model induced by a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD).

Methods: CDAHFD was administered to male C57BL/6J mice for ten weeks with or without treatment of AA extract. In this study, we evaluated biochemical markers, lipid profiles, hepatic mRNA levels, and fibrosis area. AA extract and its active components (jaceosidin, eupatilin, chlorogenic acid) were examined in vitro on human hepatic stellate LX-2 cells and mouse primary hepatic stellate cells (mHSCs). 16S rRNA sequencing, QIIME2, and PICRUST2 were employed to analyze gut microbial diversity, composition, and functional pathways.

Results: In CDAHFD-fed mice, triglyceride levels increased until 50 nmol/g (p < 0.001), while AA extract treatment decreased these levels to 41 nmol/g (p < 0.05) in the liver. Following CDAHFD-fed mice, fibrosis-related gene expression changed more than 10-fold (p < 0.01), and after AA extract treatment, it decreased 7 to 5-fold (p < 0.01, p < 0.05). In addition, AA extract treatment resulted in a significant reduction in Acetivibrio ethanolgignens abundance in the gut microbiota of CDAHFD-fed mice. The AA extract and its active components (jaceosidin, eupatilin, chlorogenic acid) inhibited fibrosis-related gene expression similarly to the control group (p < 0.01), such as Col1a1 and Acta2, which increased 2-fold upon activation of TGF-β1 in LX-2 and mHSC cells in vitro.

Conclusions: AA extract and its active components modulated NASH/fibrosis-related factors and gut microbiota composition in CDAHFD-induced liver disease. Notably, AA treatment reduced the abundance of a potentially pro-fibrotic bacterium (A. ethanolgignens). These findings support AA as a promising candidate for NASH-induced fibrosis therapy.

Funding Sources: Korea Institute of Science and Technology, grant number 2Z07021