Emodin palliates high-fat diet-induced nonalcoholic fatty liver disease in mice via activating the farnesoid X receptor pathway
| Autor: | Yuqi Si, Xiaoyi Xin, Zhijun Deng, Zhisen Pan, Shaoxiang Xian, Jiazhong Cai, Shuangcheng Wu, Qingyin Huang, Haoxiang Wu, Junmei Zhang, Hong Liu, Haitao Tu, Chuangpeng Shen, Chong Zhong, Zhangzhi Zhu, Min Liu, Mingxuan Zheng, Zhangzhou Liu, Shaoyang Lan, Yuanyuan Yu, Jiewen Guo, Yanhua Zhong |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.medical_specialty Emodin Cassia Receptors Cytoplasmic and Nuclear Diet High-Fat medicine.disease_cause Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Insulin resistance Non-alcoholic Fatty Liver Disease Internal medicine Drug Discovery Nonalcoholic fatty liver disease medicine Animals Oil Red O RNA Messenger Triglycerides 030304 developmental biology Inflammation Mice Knockout Pharmacology 0303 health sciences Dose-Response Relationship Drug Triglyceride Chemistry Fatty liver Lipid Metabolism medicine.disease Mice Inbred C57BL Oxidative Stress Glucose Endocrinology 030220 oncology & carcinogenesis Knockout mouse Hepatocytes Farnesoid X receptor Insulin Resistance Oxidative stress |
| Zdroj: | Journal of Ethnopharmacology. 279:114340 |
| ISSN: | 0378-8741 |
| DOI: | 10.1016/j.jep.2021.114340 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect