Atractylenolide III ameliorates Non-Alcoholic Fatty Liver Disease by activating Hepatic Adiponectin Receptor 1-Mediated AMPK Pathway
文献类型：期刊论文
| 作者 | Li, Qian2; Tan, Jia-Xin2; He, Yong3; Bai, Fang1,4; Li, Shi-Wei1,4; Hou, Yi-Wen2; Ji, Long-Shan2; Gao, Ya-Ting2; Zhang, Xin2; Zhou, Zhen-Hua5 |
| 刊名 | INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
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| 出版日期 | 2022 |
| 卷号 | 18期号:4页码:1594-1611 |
| ISSN号 | 1449-2288 |
| 关键词 | ATL III AdipoR1 oxidative stress inflammation AMPK SIRT1 |
| DOI | 10.7150/ijbs.68873 |
| 通讯作者 | Gao, Yue-Qiu(gaoyueqiu@hotmail.com) ; Li, Man(liman121000@shutcm.edu.cn) |
| 英文摘要 | Background: Nonalcoholic fatty liver disease (NAFLD) is the most frequent cause of chronic liver diseases worldwide. At present, there are no effective pharmacological therapies for NAFLD except lifestyle intervention-mediated weight loss. Atractylenolide III (ATL III), the major bioactive component found in Atractylode smacrocephala Koidz, has been shown to exert anti-oxidant, anti-tumor, anti-allergic response, anti-bacterial effects and cognitive protection. Here we investigate the therapeutic potential and underlying mechanisms of ATL III for the treatment of NAFLD. Methods: Male C57BL/6J mice were fed a high-fat diet (HFD) and treated with ATL III. Lipid accumulation was analyzed by Oil Red O staining in liver tissues and free fatty acids (FFAs)-treated hepatocytes. AMP-activated protein (AMPK) and sirtuin 1(SIRT1) signaling pathways were inhibited by Compound C and EX527 in vitro, respectively. Small-interfering RNA (siRNA) was used to knockdown adiponectin receptor 1 (AdipoR1) expression in HepG2 cells. Results: ATL III treatment ameliorated liver injury and hepatic lipid accumulation in the HFD-induced NAFLD mouse model as demonstrated by that ATL III administration significantly reduced serum levels of alanine aminotransferase, glutamic oxaloacetic transaminase, triglycerides, total cholesterol and low-density lipoprotein. Furthermore, treatment with ATL III alleviated hepatic oxidative stress, inflammation and fibrosis in the HFD feeding model. To study the underlying mechanisms, we performed Computer Aided Design assay and found that open-formed AdipoR1 and adiponectin receptor 2 were the potential receptors targeted by ATL III. Interestingly, HFD feeding or FFAs treatment only reduced hepatic AdipoR1 expression, while such reduction was abolished by ATL III administration. In addition, in vitro treatment with ATL III activated the AdipoR1 downstream AMPK/SIRT1 signaling pathway and reduced lipid deposition in HepG2 cells, which was diminished by silencing AdipoR1. Finally, inhibition of AMPK or SIRT1, the AdipoR1 downstream signaling, abolished the protective effects of ATL III on lipid deposition and oxidative stress in FFAs-treated HepG2 cells. Conclusion: Our findings suggest that ATL III is a therapeutic drug for the treatment of NAFLD and such protective effect is mediated by activating hepatic AdipoR1-mediated AMPK/SIRT1 signaling pathway. |
| WOS关键词 | ACCURATE DOCKING ; OXIDATIVE STRESS ; PROTEIN-KINASE ; IN-VITRO ; METABOLISM ; STEATOHEPATITIS ; ASSOCIATION ; THERAPY ; GLIDE ; CELLS |
| 资助项目 | National Natural Science Foundation of China (China)[82074155] ; National Natural Science Foundation of China (China)[81874436] ; National Natural Science Foundation of China (China)[81973773] ; Shuguang Program - Shanghai Education Development Foundation ; Shanghai Municipal Education Commission (China)[18SG39] ; Program of Shanghai Academic/Technology Research Leader (China)[SHDC2020CR3089B] ; Clinical Research Plan of SHDC (China)[SHDC2020CR3089B] ; Shanghai Key Clinical Specialty Construction Project (China)[shslczdzk01201] ; Shanghai Frontier Research Base of Disease and Syndrome Biology of inflammatory cancer transformation (China)[2021KJ03-12] ; Shanghai Sailing Program (China)[20YF1450200] ; Si Ming Foundation of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (China)[SGKJ-201912] ; Shanghai Key Laboratory of Traditional Chinese Medicine (Shanghai University of Traditional Chinese Medicine) , Ministry of Education ; Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine) , Ministry of Education |
| WOS研究方向 | Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics |
| 语种 | 英语 |
| 出版者 | IVYSPRING INT PUBL |
| WOS记录号 | WOS:000754823800021 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/300324]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Gao, Yue-Qiu; Li, Man |
| 作者单位 | 1.Shanghai Tech Univ, Shanghai Inst Adv Imrnunocherrt Studies, Shanghai, Peoples R China 2.Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Lab Cellular Immun, Shanghai, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China 4.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 5.Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Dept Hepatopathy, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Qian,Tan, Jia-Xin,He, Yong,et al. Atractylenolide III ameliorates Non-Alcoholic Fatty Liver Disease by activating Hepatic Adiponectin Receptor 1-Mediated AMPK Pathway[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,2022,18(4):1594-1611. |
| APA | Li, Qian.,Tan, Jia-Xin.,He, Yong.,Bai, Fang.,Li, Shi-Wei.,...&Li, Man.(2022).Atractylenolide III ameliorates Non-Alcoholic Fatty Liver Disease by activating Hepatic Adiponectin Receptor 1-Mediated AMPK Pathway.INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,18(4),1594-1611. |
| MLA | Li, Qian,et al."Atractylenolide III ameliorates Non-Alcoholic Fatty Liver Disease by activating Hepatic Adiponectin Receptor 1-Mediated AMPK Pathway".INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES 18.4(2022):1594-1611. |
入库方式： OAI收割
来源：上海药物研究所
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