Protective effects of Cordyceps militaris against hepatocyte apoptosis and liver fibrosis induced by high palmitic acid diet

BackgroundFatty Liver Disease (FLD) progresses from steatosis to steatohepatitis and, if left untreated, can lead to irreversible conditions such as cirrhosis and hepatocarcinoma. The etiology of FLD remains unclear, but factors such as overconsumption, poor diet, obesity, and diabetes contribute to...

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Main Authors: Wan-Ting Tsai, Jiro Hasegawa Situmorang, Wei-Wen Kuo, Chia-Hua Kuo, Shinn-Zong Lin, Chih-Yang Huang, Tsung-Jung Ho
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2024.1438997/full
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author Wan-Ting Tsai
Wan-Ting Tsai
Jiro Hasegawa Situmorang
Wei-Wen Kuo
Wei-Wen Kuo
Wei-Wen Kuo
Chia-Hua Kuo
Shinn-Zong Lin
Shinn-Zong Lin
Chih-Yang Huang
Chih-Yang Huang
Chih-Yang Huang
Chih-Yang Huang
Chih-Yang Huang
Tsung-Jung Ho
Tsung-Jung Ho
Tsung-Jung Ho
Tsung-Jung Ho
author_facet Wan-Ting Tsai
Wan-Ting Tsai
Jiro Hasegawa Situmorang
Wei-Wen Kuo
Wei-Wen Kuo
Wei-Wen Kuo
Chia-Hua Kuo
Shinn-Zong Lin
Shinn-Zong Lin
Chih-Yang Huang
Chih-Yang Huang
Chih-Yang Huang
Chih-Yang Huang
Chih-Yang Huang
Tsung-Jung Ho
Tsung-Jung Ho
Tsung-Jung Ho
Tsung-Jung Ho
author_sort Wan-Ting Tsai
collection DOAJ
description BackgroundFatty Liver Disease (FLD) progresses from steatosis to steatohepatitis and, if left untreated, can lead to irreversible conditions such as cirrhosis and hepatocarcinoma. The etiology of FLD remains unclear, but factors such as overconsumption, poor diet, obesity, and diabetes contribute to its development. Palmitic acid (PA) plays a significant role in FLD progression by inducing apoptosis, inflammation, oxidative stress, and endoplasmic reticulum (ER) stress in hepatocytes. Cordyceps militaris (CM), a fungus with various biological activities, including antioxidant properties is examined both in vitro and in vivo to assess its effectiveness in mitigating PA-induced hepatocyte apoptosis and preventing FLD progression.PurposeThis study aims to investigate the potential and mechanism of CM in combating FLD, particularly in inhibiting hepatocyte apoptosis.MethodsIn vitro studies utilized Clone9 hepatocytes treated with PA to simulate FLD conditions. The effects of CM ethyl acetate extract (EAECM) on apoptosis, mitochondrial function, ER stress, inflammation, and oxidative stress were evaluated. In vivo experiments involved FVB mice fed a NASH diet containing high levels of PA to induce FLD, with powdered CM administered orally to assess its impact on body weight, fasting blood glucose level, liver health, fibrosis, and markers of ER stress, inflammation, and oxidative stress.ResultsEAECM demonstrated protective effects against PA-induced apoptosis, mitochondrial dysfunction, ER stress, inflammation, and oxidative stress in vitro. In vivo, powdered CM supplementation attenuated body weight gain, improved fasting blood glucose level, prevented hepatomegaly, reduced serum triglycerides, and inhibited liver fibrosis. Furthermore, powdered CM treatment mitigated ER stress, inflammation, and oxidative stress in the liver of mice receiving a NASH diet.ConclusionC. militaris holds promise as a therapeutic agent for FLD, as evidenced by its ability to alleviate PA-induced hepatocytes damage and hinder FLD progression in mice. Further research is warranted to identify the active compounds responsible for its beneficial effects and to explore its potential clinical applications in treating FLD.
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spelling doaj-art-804efd15bc6b426ab632525d932ca2b82025-08-20T03:49:03ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011510.3389/fphar.2024.14389971438997Protective effects of Cordyceps militaris against hepatocyte apoptosis and liver fibrosis induced by high palmitic acid dietWan-Ting Tsai0Wan-Ting Tsai1Jiro Hasegawa Situmorang2Wei-Wen Kuo3Wei-Wen Kuo4Wei-Wen Kuo5Chia-Hua Kuo6Shinn-Zong Lin7Shinn-Zong Lin8Chih-Yang Huang9Chih-Yang Huang10Chih-Yang Huang11Chih-Yang Huang12Chih-Yang Huang13Tsung-Jung Ho14Tsung-Jung Ho15Tsung-Jung Ho16Tsung-Jung Ho17Office of Superintendent, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, TaiwanInstitute of Medical Sciences, Tzu Chi University, Hualien, TaiwanCenter for Biomedical Research, National Research and Innovation Agency (BRIN), Cibinong, IndonesiaDepartment of Biological Science and Technology, College of Life Sciences, China Medical University, Taichung, TaiwanPh.D. Program for Biotechnology Industry, China Medical University, Taichung, TaiwanSchool of Pharmacy, China Medical University, Taichung, TaiwanDepartment of Sports Sciences, University of Taipei, Taipei, TaiwanBioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien, TaiwanDepartment of Neurosurgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan0Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan1Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan2Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan3Department of Biotechnology, Asia University, Taichung, Taiwan4Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien, TaiwanInstitute of Medical Sciences, Tzu Chi University, Hualien, Taiwan5Integration Center of Traditional Chinese and Modern Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan6Department of Chinese Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan7School of Post-Baccalaureate Chinese Medicine, College of Medicine, Tzu Chi University, Hualien, TaiwanBackgroundFatty Liver Disease (FLD) progresses from steatosis to steatohepatitis and, if left untreated, can lead to irreversible conditions such as cirrhosis and hepatocarcinoma. The etiology of FLD remains unclear, but factors such as overconsumption, poor diet, obesity, and diabetes contribute to its development. Palmitic acid (PA) plays a significant role in FLD progression by inducing apoptosis, inflammation, oxidative stress, and endoplasmic reticulum (ER) stress in hepatocytes. Cordyceps militaris (CM), a fungus with various biological activities, including antioxidant properties is examined both in vitro and in vivo to assess its effectiveness in mitigating PA-induced hepatocyte apoptosis and preventing FLD progression.PurposeThis study aims to investigate the potential and mechanism of CM in combating FLD, particularly in inhibiting hepatocyte apoptosis.MethodsIn vitro studies utilized Clone9 hepatocytes treated with PA to simulate FLD conditions. The effects of CM ethyl acetate extract (EAECM) on apoptosis, mitochondrial function, ER stress, inflammation, and oxidative stress were evaluated. In vivo experiments involved FVB mice fed a NASH diet containing high levels of PA to induce FLD, with powdered CM administered orally to assess its impact on body weight, fasting blood glucose level, liver health, fibrosis, and markers of ER stress, inflammation, and oxidative stress.ResultsEAECM demonstrated protective effects against PA-induced apoptosis, mitochondrial dysfunction, ER stress, inflammation, and oxidative stress in vitro. In vivo, powdered CM supplementation attenuated body weight gain, improved fasting blood glucose level, prevented hepatomegaly, reduced serum triglycerides, and inhibited liver fibrosis. Furthermore, powdered CM treatment mitigated ER stress, inflammation, and oxidative stress in the liver of mice receiving a NASH diet.ConclusionC. militaris holds promise as a therapeutic agent for FLD, as evidenced by its ability to alleviate PA-induced hepatocytes damage and hinder FLD progression in mice. Further research is warranted to identify the active compounds responsible for its beneficial effects and to explore its potential clinical applications in treating FLD.https://www.frontiersin.org/articles/10.3389/fphar.2024.1438997/fullfatty liver diseaseCordyceps militarisliver fibrosispalmitic acidhepatocyte apoptosismitochondrial dysfunction
spellingShingle Wan-Ting Tsai
Wan-Ting Tsai
Jiro Hasegawa Situmorang
Wei-Wen Kuo
Wei-Wen Kuo
Wei-Wen Kuo
Chia-Hua Kuo
Shinn-Zong Lin
Shinn-Zong Lin
Chih-Yang Huang
Chih-Yang Huang
Chih-Yang Huang
Chih-Yang Huang
Chih-Yang Huang
Tsung-Jung Ho
Tsung-Jung Ho
Tsung-Jung Ho
Tsung-Jung Ho
Protective effects of Cordyceps militaris against hepatocyte apoptosis and liver fibrosis induced by high palmitic acid diet
Frontiers in Pharmacology
fatty liver disease
Cordyceps militaris
liver fibrosis
palmitic acid
hepatocyte apoptosis
mitochondrial dysfunction
title Protective effects of Cordyceps militaris against hepatocyte apoptosis and liver fibrosis induced by high palmitic acid diet
title_full Protective effects of Cordyceps militaris against hepatocyte apoptosis and liver fibrosis induced by high palmitic acid diet
title_fullStr Protective effects of Cordyceps militaris against hepatocyte apoptosis and liver fibrosis induced by high palmitic acid diet
title_full_unstemmed Protective effects of Cordyceps militaris against hepatocyte apoptosis and liver fibrosis induced by high palmitic acid diet
title_short Protective effects of Cordyceps militaris against hepatocyte apoptosis and liver fibrosis induced by high palmitic acid diet
title_sort protective effects of cordyceps militaris against hepatocyte apoptosis and liver fibrosis induced by high palmitic acid diet
topic fatty liver disease
Cordyceps militaris
liver fibrosis
palmitic acid
hepatocyte apoptosis
mitochondrial dysfunction
url https://www.frontiersin.org/articles/10.3389/fphar.2024.1438997/full
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