Chuangpeng Shen1, Zhisen Pan2, Shuangcheng Wu2, Mingxuan Zheng3, Chong Zhong4, Xiaoyi Xin5, Shaoyang Lan6, Zhangzhi Zhu6, Min Liu6, Haoxiang Wu6, Qingyin Huang6, Junmei Zhang6, Zhangzhou Liu6, Yuqi Si2, Haitao Tu6, Zhijun Deng7, Yuanyuan Yu8, Hong Liu9, Yanhua Zhong10, Jiewen Guo11, Jiazhong Cai12, Shaoxiang Xian13. 1. The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China; Department of Endocrinology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China; The First People's Hospital of Kashgar Prefecture, Kashgar, Xinjiang Uygur Autonomous Region, China; The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China. 2. The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China. 3. Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical University, Xuzhou, China. 4. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. 5. The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China. 6. Department of Endocrinology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. 7. Department of Science and Education, Guangzhou Hospital of Traditional Chinese Medicine, Guangzhou, China. 8. Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China. 9. Department of Ophthalmology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. 10. Department of Acupuncture-rehabilitation, Guangzhou-Liwan Hospital of Chinese Medicine, Guangzhou, China. Electronic address: 281700518@qq.com. 11. Department of Science and Education, Guangzhou Hospital of Traditional Chinese Medicine, Guangzhou, China. Electronic address: gzszyykjk@gz.gov.cn. 12. Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China. Electronic address: jiazhongcai@gzucm.edu.cn. 13. The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China. Electronic address: zhongyfy@126.com.
Abstract
BACKGROUND: Cassia mimosoides Linn (CMD) is a traditional Chinese herb that clears liver heat and dampness. It has been widely administered in clinical practice to treat jaundice associated with damp-heat pathogen and obesity. Emodin (EMO) is a major bioactive constituent of CMD that has apparent therapeutic efficacy against obesity and fatty liver. Here, we investigated the protective effects and underlying mechanisms of EMO against high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD). OBJECTIVE: We aimed to investigate whether EMO activates farnesoid X receptor (FXR) signaling to alleviate HFD-induced NAFLD. MATERIALS AND METHODS: In vivo assays included serum biochemical indices tests, histopathology, western blotting, and qRT-PCR to evaluate the effects of EMO on glucose and lipid metabolism disorders in wild type (WT) and FXR knockout mice maintained on an HFD. In vitro experiments included intracellular triglyceride (TG) level measurement and Oil Red O staining to assess the capacity of EMO to remove lipids induced by oleic acid and palmitic acid in WT and FXR knockout mouse primary hepatocytes (MPHs). We also detected mRNA expression of FXR signaling genes in MPHs. RESULTS: After HFD administration, body weight and serum lipid and inflammation levels were dramatically increased in the WT mice. The animals also presented with impaired glucose tolerance, insulin resistance, and antioxidant capacity, liver tissue attenuation, and pathological injury. EMO remarkably reversed the foregoing changes in HFD-induced mice. EMO improved HFD-induced lipid accumulation, insulin resistance, inflammation, and oxidative stress in a dose-dependent manner in WT mice by inhibiting FXR expression. EMO also significantly repressed TG hyperaccumulation by upregulating FXR expression in MPHs. However, it did not improve lipid accumulation, insulin sensitivity, or glucose tolerance in HFD-fed FXR knockout mice. CONCLUSIONS: The present study demonstrated that EMO alleviates HFD-induced NAFLD by activating FXR signaling which improves lipid accumulation, insulin resistance, inflammation, and oxidative stress.
BACKGROUND: Cassia mimosoides Linn (CMD) is a traditional Chinese herb that clears liver heat and dampness. It has been widely administered in clinical practice to treat jaundice associated with damp-heat pathogen and obesity. Emodin (EMO) is a major bioactive constituent of CMD that has apparent therapeutic efficacy against obesity and fatty liver. Here, we investigated the protective effects and underlying mechanisms of EMO against high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD). OBJECTIVE: We aimed to investigate whether EMO activates farnesoid X receptor (FXR) signaling to alleviate HFD-induced NAFLD. MATERIALS AND METHODS: In vivo assays included serum biochemical indices tests, histopathology, western blotting, and qRT-PCR to evaluate the effects of EMO on glucose and lipid metabolism disorders in wild type (WT) and FXR knockout mice maintained on an HFD. In vitro experiments included intracellular triglyceride (TG) level measurement and Oil Red O staining to assess the capacity of EMO to remove lipids induced by oleic acid and palmitic acid in WT and FXR knockout mouse primary hepatocytes (MPHs). We also detected mRNA expression of FXR signaling genes in MPHs. RESULTS: After HFD administration, body weight and serum lipid and inflammation levels were dramatically increased in the WT mice. The animals also presented with impaired glucose tolerance, insulin resistance, and antioxidant capacity, liver tissue attenuation, and pathological injury. EMO remarkably reversed the foregoing changes in HFD-induced mice. EMO improved HFD-induced lipid accumulation, insulin resistance, inflammation, and oxidative stress in a dose-dependent manner in WT mice by inhibiting FXR expression. EMO also significantly repressed TG hyperaccumulation by upregulating FXR expression in MPHs. However, it did not improve lipid accumulation, insulin sensitivity, or glucose tolerance in HFD-fed FXR knockout mice. CONCLUSIONS: The present study demonstrated that EMO alleviates HFD-induced NAFLD by activating FXR signaling which improves lipid accumulation, insulin resistance, inflammation, and oxidative stress.