start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=13 article-no= start-page=7238 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250627 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Protective Effects of the Ethyl Acetate Fraction of Distylium racemosum Against Metabolic Dysfunction-Associated Steatohepatitis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Metabolic dysfunction-associated steatohepatitis (MASH), previously referred to as non-alcoholic steatohepatitis (NASH), which is a progressive non-alcoholic fatty liver disease, is accompanied by hepatic steatosis, inflammation, and fibrosis. Despite its increasing prevalence, available treatment options for MASH are limited. Here, we investigated the protective effects of the Distylium racemosum ethyl acetate fraction (DRE) using MASH models and explored its key physiologically active components. Palmitic acid (PA)-induced AML12 hepatocytes and high-fat methionine- and choline-deficient-fed C57BL/6 mice were used as MASH models. Lipid accumulation was evaluated via triglyceride measurement, oil red O staining, and histological analysis. Lipid accumulation, inflammation, and fibrosis-associated gene expression were evaluated via real-time polymerase chain reaction. The physiologically active components of DRE were identified via high-performance liquid chromatography. Lipid accumulation and triglyceride levels were significantly reduced in PA-treated AML12 cells following DRE treatment. Additionally, DRE inhibited the expression of genes involved in lipogenesis (FAS and SREBP1c), inflammation (CD68, IL-6, and MCP-1), and fibrosis (COL1A1, COL1A2, and TIMP1). DRE reduced the liver weight, liver-to-body weight ratio, and hepatic steatosis in MASH model mice. It increased carnitine palmitoyltransferase-1 levels and decreased CD36 and transforming growth factor-β levels in the MASH mouse liver. High-performance liquid chromatography revealed that the extract contained rutin flavonoid family members. Overall, DRE was involved in lipid metabolism, inflammation, and fibrosis regulation, exerting potent hepatoprotective effects partly attributed to rutin and serving as a potential preventive candidate for MASH. en-copyright= kn-copyright= en-aut-name=LeeYoung-Hyeon en-aut-sei=Lee en-aut-mei=Young-Hyeon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YeoMin-Ho en-aut-sei=Yeo en-aut-mei=Min-Ho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ChangKyung-Soo en-aut-sei=Chang en-aut-mei=Kyung-Soo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoonWeon-Jong en-aut-sei=Yoon en-aut-mei=Weon-Jong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KimHye-Sook en-aut-sei=Kim en-aut-mei=Hye-Sook kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KimJongwan en-aut-sei=Kim en-aut-mei=Jongwan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KimHye-Ran en-aut-sei=Kim en-aut-mei=Hye-Ran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Clinical Laboratory Science, Catholic University of Pusan kn-affil= affil-num=2 en-affil=Department of Clinical Laboratory Science, Catholic University of Pusan kn-affil= affil-num=3 en-affil=Department of Clinical Laboratory Science, Catholic University of Pusan kn-affil= affil-num=4 en-affil=Clean Bio Business Division, Biodiversity Research Institute (JBRI), Jeju Technopark (JTP) kn-affil= affil-num=5 en-affil=Department of International Infectious Diseases Control, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Anatomy, College of Medicine, Dongguk University kn-affil= affil-num=7 en-affil=Department of Biomedical Laboratory Science, Dong-Eui Institute of Technology kn-affil= en-keyword=metabolic dysfunction-associated steatohepatitis kn-keyword=metabolic dysfunction-associated steatohepatitis en-keyword=Distylium racemosum kn-keyword=Distylium racemosum en-keyword=ethyl acetate fraction kn-keyword=ethyl acetate fraction en-keyword=extract kn-keyword=extract END