Arctigenin induces activated HSCs quiescence via AMPK-PPARγ pathway to ameliorate liver fibrosis in mice
文献类型：期刊论文
| 作者 | Lv, Mengjia1,2,3; Chen, Shiyi1,2,3; Shan, Mengwen1,2,3; Si, Yuan1,2; Huang, Chenggang2 ; Chen, Jing1,2,3; Gong, Likun1,2,3
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| 刊名 | EUROPEAN JOURNAL OF PHARMACOLOGY
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| 出版日期 | 2024-07-05 |
| 卷号 | 974页码:10 |
| 关键词 | Liver fibrosis Arctigenin Hepatic stellate cell (HSC) AMPK PPAR gamma |
| ISSN号 | 0014-2999 |
| DOI | 10.1016/j.ejphar.2024.176629 |
| 通讯作者 | Huang, Chenggang(cghuang@simm.ac.cn) ; Chen, Jing(jingchen@simm.ac.cn) ; Gong, Likun(lkgong@simm.ac.cn) |
| 英文摘要 | Arctigenin (ATG), a traditional Chinese herbal medicine, is a natural lignan compound extracted from the seeds of burdock (Arctium lappa L, Asteraceae). As a natural product with multiple biological activities, the effect and mechanism of ATG against liver fibrosis are not fully elucidated yet. In current work, we first discovered that ATG could improve CCl4-induced liver injury reflected by lower plasma ALT and AST levels, liver coefficient and pathological scoring of ballooning. Furthermore, it also could reduce the positive areas of Masson, Sirius red and alpha-SMA staining, inhibit the expression of fibrosis-related genes (Col1a1, Col3a1, Acta2), and decrease the content of hydroxyproline, indicated ATG treatment had benefits in alleviating CCl4-induced liver fibrosis. In vitro, we observed that ATG can inhibit collagen production stimulated by TGF-beta 1 in LX2 cells. By analysis of the information obtained from SymMap and GeneCards databases and in vitro validation experiments, ATG was proven to be an indirect PPAR gamma agonist and its effect on collagen production was dependent on PPAR gamma. Subsequently, we confirmed that ATG activating AMPK was the contributor of its effect on PPAR gamma and collagen production. Finally, the transformation of activated hepatic stellate cells was determined after treated with ATG, in which ATG treatment could return activated LX2 cells to quiescence because of the elevated quiescent markers and lipid droplets. Our work has highlighted the potential of ATG in the treatment of liver fibrosis and clarified that ATG can activate AMPK/PPAR gamma pathway to restore the activated hepatic stellate cell to quiescence thereby improving liver fibrosis. |
| WOS关键词 | HEPATIC STELLATE CELLS |
| 资助项目 | National Natural Science Foundation of China[82370575] ; Foundation of Shanghai Science and Technology Committee[21DZ2291100] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001237319800001 |
| 出版者 | ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/311800]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Huang, Chenggang; Chen, Jing; Gong, Likun |
| 作者单位 | 1.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201203, Peoples R China 3.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China |
| 推荐引用方式 GB/T 7714 | Lv, Mengjia,Chen, Shiyi,Shan, Mengwen,et al. Arctigenin induces activated HSCs quiescence via AMPK-PPARγ pathway to ameliorate liver fibrosis in mice[J]. EUROPEAN JOURNAL OF PHARMACOLOGY,2024,974:10. |
| APA | Lv, Mengjia.,Chen, Shiyi.,Shan, Mengwen.,Si, Yuan.,Huang, Chenggang.,...&Gong, Likun.(2024).Arctigenin induces activated HSCs quiescence via AMPK-PPARγ pathway to ameliorate liver fibrosis in mice.EUROPEAN JOURNAL OF PHARMACOLOGY,974,10. |
| MLA | Lv, Mengjia,et al."Arctigenin induces activated HSCs quiescence via AMPK-PPARγ pathway to ameliorate liver fibrosis in mice".EUROPEAN JOURNAL OF PHARMACOLOGY 974(2024):10. |
入库方式： OAI收割
来源：上海药物研究所
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