Marine natural product des-O-methyllasiodiplodin effectively lowers the blood glucose level in db/db mice via ameliorating inflammation
文献类型：期刊论文
| 作者 | Zhou, Rong1; Lin, Zhong-hui2; Jiang, Cheng-shi2; Gong, Jing-xu2; Chen, Li-li2 ; Guo, Yue-wei2; Shen, Xu1,2
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2013-10 |
| 卷号 | 34期号:10页码:1325-1336 |
| 关键词 | des-O-methyllasiodiplodin diabetes db/db mice pro-inflammatory cytokine ROS mineralocorticoid receptor aldosterone blood glucose glycosylated hemoglobin (HbA1c) |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2013.47 |
| 文献子类 | Article |
| 英文摘要 | Aim: des-O-methyllasiodiplodin (DML) from Cerbera manghas has shown antagonistic activity against mineralocorticoid receptor (MR). Considering the involvement of MR in the insulin tolerance, we attempted to investigate the potential of DML in the treatment of type 2 diabetes mellitus (T2DM). Methods: Surface plasmon resonance (SPR) technology and reporter gene-based assays were used to study protein-small molecule interactions. HepG2 and 3T3-L1 cells were treated with H2O2 (0.2 mmol/L) or aldosterone (10 nmol/L) for 24 h. The expression of MR in the cells was downregulated with siRNA. The anti-inflammatory effect of the compound was evaluated, respectively. db/db mice were administered DML (30 mg.kg(-1).d(-1)) for 4 weeks. Serum biochemical parameters and insulin sensitivity were examined. The expression levels of pro-inflammatory cytokines (MCP-1, TNF-alpha, and IL-6) and ROS-related genes (NADPH p47 subunit and transcriptional factor PU.1) in adipose tissues and livers were analyzed using real-time RT-PCR. Results: In HepG2 and 3T3-L1 cells, both H2O2 and aldosterone markedly stimulates the expression of MCP-1, TNF alpha, IL-6, p47, and PU.1 genes. Co-treatment with DML (10 mu mol/L) significantly reduced the H2O2- or aldosterone-induced expression of these genes. SPR-based assay confirmed the antagonistic activity of DML against the interaction between SRC-1 and MR-LBD. Furthermore, DML decreased aldosterone-induced MR transcriptional activity in a dose-dependent manner. Downregulation of MR with siRNA in the cells prevented or significantly attenuated aldosterone-stimulated expression of these genes, whereas DML did no longer affect the expression of these genes except that of IL-6. Oral administration of DML effectively reduced the levels of blood glucose and glycosylated hemoglobin (HbA1c) in db/db mice. The treatment also rectified the expression of pro-inflammatory factor and ROS-related genes in db/db mice. Conclusion: DML effectively lowers the blood glucose level in db/db mice possibly via ameliorating the expression of obesity-related pro-inflammatory cytokines, highlighting the potential of the marine natural product as a drug lead for the treatment of metabolic disorders. |
| WOS关键词 | TYPE-2 DIABETES-MELLITUS ; MINERALOCORTICOID RECEPTOR ; INSULIN-RESISTANCE ; PRIMARY ALDOSTERONISM ; METABOLIC SYNDROME ; LIPID-METABOLISM ; CERBERA-MANGHAS ; NADPH OXIDASE ; C-SRC ; OBESITY |
| 资助项目 | National Marine 863 Programme[2011AA09070102] ; National Natural Science Foundation of China[81173105] ; National Natural Science Foundation of China[91213306] ; National Science and Technology Major Project[2012ZX09301001-004] ; National Science and Technology Major Project[2012ZX09103101-18] ; Foundation of Chinese Academy of Sciences[KSCX2-EW-Q-3] ; Science Foundation of Shanghai[11XD1406100] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:4935196 |
| WOS记录号 | WOS:000325276400009 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277442]  |
| 专题 | 生物技术药物研发中心（筹） 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 天然药物化学研究室 药理学第三研究室 |
| 通讯作者 | Chen, Li-li |
| 作者单位 | 1.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China; 2.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhou, Rong,Lin, Zhong-hui,Jiang, Cheng-shi,et al. Marine natural product des-O-methyllasiodiplodin effectively lowers the blood glucose level in db/db mice via ameliorating inflammation[J]. ACTA PHARMACOLOGICA SINICA,2013,34(10):1325-1336. |
| APA | Zhou, Rong.,Lin, Zhong-hui.,Jiang, Cheng-shi.,Gong, Jing-xu.,Chen, Li-li.,...&Shen, Xu.(2013).Marine natural product des-O-methyllasiodiplodin effectively lowers the blood glucose level in db/db mice via ameliorating inflammation.ACTA PHARMACOLOGICA SINICA,34(10),1325-1336. |
| MLA | Zhou, Rong,et al."Marine natural product des-O-methyllasiodiplodin effectively lowers the blood glucose level in db/db mice via ameliorating inflammation".ACTA PHARMACOLOGICA SINICA 34.10(2013):1325-1336. |
入库方式： OAI收割
来源：上海药物研究所
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