Erdenebileg, Saruul Kim, Myung Suk Nam, Yunseong Cha, Kwang Hyun Le, Tam Thi Jung, Sang Hoon Nho, Chu Won 2024-06-14T05:00:14Z 2024-06-14T05:00:14Z 2024-06-13 2024-10 0378-8741 https://pubs.kist.re.kr/handle/201004/150082 Ethnopharmacological relevance Artemisia argyi (AA), a herbal medicine traditionally used in Asian countries, to treat inflammatory conditions such as eczema, dermatitis, arthritis, allergic asthma and colitis. However, the mechanism of action of this plant with regard to hepatitis and other liver-related diseases is still unclear. Aim This study aimed to investigate the effects of AA ethanol extract on NASH-related fibrosis and gut microbiota in a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD)-induced mouse model. Methods Male C57BL/6J mice were fed CDAHFD, with or without AA ethanol extract treatment. Biochemical markers, lipid profiles, hepatic mRNA expression levels of key genes, and the fibrosis area were assessed. In vitro, TGF-β-stimulated human hepatic stellate LX-2 cells and mouse primary hepatic stellate cells (mHSCs) were used to elucidate the effects of AA ethanol extract on fibrosis and steatosis. 16S rRNA sequencing, QIIME2, and PICRUST2 were employed to analyze gut microbial diversity, composition, and functional pathways. Results Treatment with the AA ethanol extract improved plasma and liver lipid profiles, modulated hepatic mRNA expression levels of antioxidant, lipolytic, and fibrosis-related genes, and significantly reduced CDAHFD-induced hepatic fibrosis. Gut microbiota analysis revealed a marked decrease in Acetivibrio ethanolgignens abundance upon treatment with the AA ethanol extract, and its functional pathways were significantly correlated with NASH/fibrosis markers. The AA ethanol extract and its active components (jaceosidin, eupatilin, and chlorogenic acid) inhibited fibrosis-related markers in LX-2 and mHSC. Conclusion The AA ethanol extract exerted therapeutic effects on CDAHFD-induced liver disease by modulating NASH/fibrosis-related factors and gut microbiota composition. Notably, AA treatment reduced the abundance of the potentially profibrotic bacterium (A. ethanolgignens). These findings suggest that AA is a promising candidate for treating NASH-induced fibrosis. English Elsevier BV Artemisia argyi ethanol extract ameliorates nonalcoholic steatohepatitis-induced liver fibrosis by modulating gut microbiota and hepatic signaling Article 10.1016/j.jep.2024.118415 1 Journal of Ethnopharmacology, v.333 Journal of Ethnopharmacology 333 N scie scopus 001253763900001 Plant Sciences Chemistry, Medicinal Integrative & Complementary Medicine Pharmacology & Pharmacy Plant Sciences Pharmacology & Pharmacy Integrative & Complementary Medicine Article KUPFFER CELLS DISEASE COMBINATION MECHANISMS EXPRESSION RESOLUTION STEATOSIS EUPATILIN STRESS MODEL Fibrosis Nonalcoholic steatohepatitis Artemisia argyi Choline-deficient-L-amino-acid-defined High -fat diet Gut microbiome