Leukamenin F suppresses liver fibrogenesis by inhibiting both hepatic stellate cell proliferation and extracellular matrix production
文献类型：期刊论文
| 作者 | Liu, Qiong; Wang, Xu; Zhang, Yu; Li, Chen-jing; Hu, Li-hong; Shen, Xu
|
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2010-07 |
| 卷号 | 31期号:7页码:839-848 |
| 关键词 | Leukamenin F liver fibrosis carbon tetrachloride hepatic stellate cells Akt collagen |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2010.64 |
| 文献子类 | Article |
| 英文摘要 | Aim: To investigate the inhibitory effect of the natural product Leukamenin F on liver fibrosis and explore its potential underlying mechanisms. Methods: Carbon tetrachloride (CCl4)-treated mouse model in vivo and in hepatic stellate cells (HSC) in vitro were used. The effect on CCl4-induced liver fibrosis was studied using histochemical and biochemical analysis, while the inhibition on HSC was assessed using cell proliferation/apoptosis assay and collagen I production using real-time PCR. The inhibitory effects of Leukamenin F on Akt/mTOR/p70S6K and TGF beta/Smad pathways was studied using Western blot and cell image analysis. Results: Leukamenin F (0.1-1 mg/kg, ip, q.d.x28) significantly reduced alpha-SMA and collagen specific Sirius red staining areas in CCl4-treated mouse livers. This compound at 1-2 mu mol/L dose-dependently inhibited a-SMA expression, cell proliferation and type I procollagen mRNA expression in activated HSC. Furthermore it inhibited the Akt/mTOR/p70S6K pathway and suppressed TGF alpha-induced Smad2/Smad3 phosphorylation and nuclear translocation in HSC. Conclusion: Our results demonstrated that Leukamenin F could attenuate CCl4-induced liver fibrogenesis in mice as an efficient inhibitor against both HSC proliferation and ECM production. This natural product provides a valuable structural hint for the development of anti-liver fibrosis reagents. |
| WOS关键词 | FIBROSIS ; GROWTH ; EXPRESSION ; PHOSPHORYLATION ; MECHANISMS ; ACTIVATION ; RAPAMYCIN ; P70(S6K) ; INSIGHTS ; CANCER |
| 资助项目 | State Key Program of Basic Research of China[2010CB912501] ; State Key Program of Basic Research of China[2007CB914304] ; National Natural Science Foundation of China[30890044] ; National Natural Science Foundation of China[20721003] ; Key New Drug Creation and Manufacturing Program[2009ZX09301-001] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:3893620 |
| WOS记录号 | WOS:000279538400010 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278842]  |
| 专题 | 上海中药现代化研究中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药理学第三研究室 |
| 通讯作者 | Hu, Li-hong |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Qiong,Wang, Xu,Zhang, Yu,et al. Leukamenin F suppresses liver fibrogenesis by inhibiting both hepatic stellate cell proliferation and extracellular matrix production[J]. ACTA PHARMACOLOGICA SINICA,2010,31(7):839-848. |
| APA | Liu, Qiong,Wang, Xu,Zhang, Yu,Li, Chen-jing,Hu, Li-hong,&Shen, Xu.(2010).Leukamenin F suppresses liver fibrogenesis by inhibiting both hepatic stellate cell proliferation and extracellular matrix production.ACTA PHARMACOLOGICA SINICA,31(7),839-848. |
| MLA | Liu, Qiong,et al."Leukamenin F suppresses liver fibrogenesis by inhibiting both hepatic stellate cell proliferation and extracellular matrix production".ACTA PHARMACOLOGICA SINICA 31.7(2010):839-848. |
入库方式： OAI收割
来源：上海药物研究所
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