Protective Effects of the Ethyl Acetate Fraction of <i>Distylium racemosum</i> Against Metabolic Dysfunction-Associated Steatohepatitis

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 o...

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Main Authors: Young-Hyeon Lee, Min-Ho Yeo, Kyung-Soo Chang, Weon-Jong Yoon, Hye-Sook Kim, Jongwan Kim, Hye-Ran Kim
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Applied Sciences
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Online Access:https://www.mdpi.com/2076-3417/15/13/7238
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author Young-Hyeon Lee
Min-Ho Yeo
Kyung-Soo Chang
Weon-Jong Yoon
Hye-Sook Kim
Jongwan Kim
Hye-Ran Kim
author_facet Young-Hyeon Lee
Min-Ho Yeo
Kyung-Soo Chang
Weon-Jong Yoon
Hye-Sook Kim
Jongwan Kim
Hye-Ran Kim
author_sort Young-Hyeon Lee
collection DOAJ
description 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 <i>Distylium racemosum</i> 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 (<i>FAS</i> and <i>SREBP1c</i>), inflammation <i>(CD68</i>, <i>IL-6</i>, and <i>MCP-1</i>), and fibrosis (<i>COL1A1</i>, <i>COL1A2</i>, and <i>TIMP1</i>). 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 <i>CD36</i> 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.
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spelling doaj-art-01eba8b5db5540e68246c7a6447a4e442025-08-20T03:28:36ZengMDPI AGApplied Sciences2076-34172025-06-011513723810.3390/app15137238Protective Effects of the Ethyl Acetate Fraction of <i>Distylium racemosum</i> Against Metabolic Dysfunction-Associated SteatohepatitisYoung-Hyeon Lee0Min-Ho Yeo1Kyung-Soo Chang2Weon-Jong Yoon3Hye-Sook Kim4Jongwan Kim5Hye-Ran Kim6Department of Clinical Laboratory Science, Catholic University of Pusan, Busan 46252, Republic of KoreaDepartment of Clinical Laboratory Science, Catholic University of Pusan, Busan 46252, Republic of KoreaDepartment of Clinical Laboratory Science, Catholic University of Pusan, Busan 46252, Republic of KoreaClean Bio Business Division, Biodiversity Research Institute (JBRI), Jeju Technopark (JTP), Seogwipo 63608, Republic of KoreaDepartment of International Infectious Diseases Control, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Tsushima-Naka, Kita-Ku, Okayama 700-8530, JapanDepartment of Anatomy, College of Medicine, Dongguk University, Gyeongju 38066, Republic of KoreaDepartment of Biomedical Laboratory Science, Dong-Eui Institute of Technology, Busan 47230, Republic of KoreaMetabolic 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 <i>Distylium racemosum</i> 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 (<i>FAS</i> and <i>SREBP1c</i>), inflammation <i>(CD68</i>, <i>IL-6</i>, and <i>MCP-1</i>), and fibrosis (<i>COL1A1</i>, <i>COL1A2</i>, and <i>TIMP1</i>). 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 <i>CD36</i> 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.https://www.mdpi.com/2076-3417/15/13/7238metabolic dysfunction-associated steatohepatitis<i>Distylium racemosum</i>ethyl acetate fractionextract
spellingShingle Young-Hyeon Lee
Min-Ho Yeo
Kyung-Soo Chang
Weon-Jong Yoon
Hye-Sook Kim
Jongwan Kim
Hye-Ran Kim
Protective Effects of the Ethyl Acetate Fraction of <i>Distylium racemosum</i> Against Metabolic Dysfunction-Associated Steatohepatitis
Applied Sciences
metabolic dysfunction-associated steatohepatitis
<i>Distylium racemosum</i>
ethyl acetate fraction
extract
title Protective Effects of the Ethyl Acetate Fraction of <i>Distylium racemosum</i> Against Metabolic Dysfunction-Associated Steatohepatitis
title_full Protective Effects of the Ethyl Acetate Fraction of <i>Distylium racemosum</i> Against Metabolic Dysfunction-Associated Steatohepatitis
title_fullStr Protective Effects of the Ethyl Acetate Fraction of <i>Distylium racemosum</i> Against Metabolic Dysfunction-Associated Steatohepatitis
title_full_unstemmed Protective Effects of the Ethyl Acetate Fraction of <i>Distylium racemosum</i> Against Metabolic Dysfunction-Associated Steatohepatitis
title_short Protective Effects of the Ethyl Acetate Fraction of <i>Distylium racemosum</i> Against Metabolic Dysfunction-Associated Steatohepatitis
title_sort protective effects of the ethyl acetate fraction of i distylium racemosum i against metabolic dysfunction associated steatohepatitis
topic metabolic dysfunction-associated steatohepatitis
<i>Distylium racemosum</i>
ethyl acetate fraction
extract
url https://www.mdpi.com/2076-3417/15/13/7238
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