| HPN, a Synthetic Analogue of Bromophenol from Red Alga Rhodomela confervoides: Synthesis and Anti-Diabetic Effects in C57BL/KsJ-db/db Mice | |
| Shi, Dayong1,2; Guo, Shuju1,2; Jiang, Bo1,2; Guo, Chao1,2; Wang, Tao3; Zhang, Luyong3; Li, Jingya4; Shi, DY | |
| 2013-02-01 | |
| 发表期刊 | MARINE DRUGS
 |
| ISSN | 1660-3397 |
| 卷号 | 11期号:2页码:350-362 |
| 文章类型 | Article |
| 摘要 | 3,4-Dibromo-5-(2-bromo-3,4-dihydroxy-6-(isopropoxymethyl)benzyl)benzene-1,2-diol (HPN) is a synthetic analogue of 3,4-dibromo-5-(2-bromo-3,4-dihydroxy-6-(ethoxymethyl) benzyl)benzene-1,2-diol (BPN), which is isolated from marine red alga Rhodomela confervoides with potent protein tyrosine phosphatase 1B (PTP1B) inhibition (IC50 = 0.84 mu mol/L). The in vitro assay showed that HPN exhibited enhanced inhibitory activity against PTP1B with IC50 0.63 mu mol/L and high selectivity against other PTPs (T cell protein tyrosine phosphatase (TCPTP), leucocyte antigen-related tyrosine phosphatase (LAR), Src homology 2-containing protein tyrosine phosphatase-1 (SHP-1) and SHP-2). The results of antihyperglycemic activity using db/db mouse model demonstrated that HPN significantly decreased plasma glucose (P < 0.01) after eight weeks treatment period. HPN lowered serum triglycerides and total cholesterol concentration in a dose-dependent manner. Besides, both of the high and medium dose groups of HPN remarkably decreased HbA1c levels (P < 0.05). HPN in the high dose group markedly lowered the insulin level compared to the model group (P < 0.05), whereas the effects were less potent than the positive drug rosiglitazone. Western blotting results showed that HPN decreased PTP1B levels in pancreatic tissue. Last but not least, the results of an intraperitoneal glucose tolerance test in Sprague-Dawley rats indicate that HPN have a similar antihyperglycemic activity as rosiglitazone. HPN therefore have potential for development as treatments for Type 2 diabetes.; 3,4-Dibromo-5-(2-bromo-3,4-dihydroxy-6-(isopropoxymethyl)benzyl)benzene-1,2-diol (HPN) is a synthetic analogue of 3,4-dibromo-5-(2-bromo-3,4-dihydroxy-6-(ethoxymethyl) benzyl)benzene-1,2-diol (BPN), which is isolated from marine red alga Rhodomela confervoides with potent protein tyrosine phosphatase 1B (PTP1B) inhibition (IC50 = 0.84 mu mol/L). The in vitro assay showed that HPN exhibited enhanced inhibitory activity against PTP1B with IC50 0.63 mu mol/L and high selectivity against other PTPs (T cell protein tyrosine phosphatase (TCPTP), leucocyte antigen-related tyrosine phosphatase (LAR), Src homology 2-containing protein tyrosine phosphatase-1 (SHP-1) and SHP-2). The results of antihyperglycemic activity using db/db mouse model demonstrated that HPN significantly decreased plasma glucose (P < 0.01) after eight weeks treatment period. HPN lowered serum triglycerides and total cholesterol concentration in a dose-dependent manner. Besides, both of the high and medium dose groups of HPN remarkably decreased HbA1c levels (P < 0.05). HPN in the high dose group markedly lowered the insulin level compared to the model group (P < 0.05), whereas the effects were less potent than the positive drug rosiglitazone. Western blotting results showed that HPN decreased PTP1B levels in pancreatic tissue. Last but not least, the results of an intraperitoneal glucose tolerance test in Sprague-Dawley rats indicate that HPN have a similar antihyperglycemic activity as rosiglitazone. HPN therefore have potential for development as treatments for Type 2 diabetes. |
| 关键词 | Bromophenol Protein Tyrosine Phosphatase 1b Inhibitor Db/db Mouse Model Anti-diabetes Properties |
| 学科领域 | Pharmacology & Pharmacy |
| DOI | 10.3390/md11020350 |
| URL | 查看原文 |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS研究方向 | Pharmacology & Pharmacy |
| WOS类目 | Chemistry, Medicinal |
| WOS记录号 | WOS:000315396800005 |
| WOS关键词 | TYROSINE-PHOSPHATASE 1B ; PTP1B INHIBITORS ; BIOLOGICAL EVALUATION ; INSULIN SENSITIVITY ; ACID-DERIVATIVES ; DRUGS ; SESQUITERPENES ; DESIGN |
| WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://ir.qdio.ac.cn/handle/337002/16704 |
| 专题 | 海洋生物技术研发中心 |
| 通讯作者 | Shi, DY |
| 作者单位 | 1.Chinese Acad Sci, Inst Oceanol, Qingdao 266071, Peoples R China 2.Chinese Acad Sci, Nantong Branch, Inst Oceanol, Nantong 226006, Peoples R China 3.China Pharmaceut Univ, Jiangsu Ctr Drug Screening, Nanjing 210009, Jiangsu, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Inst Biol Sci, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China |
| 第一作者单位 | 中国科学院海洋研究所 |
| 推荐引用方式 GB/T 7714 | Shi, Dayong,Guo, Shuju,Jiang, Bo,et al. HPN, a Synthetic Analogue of Bromophenol from Red Alga Rhodomela confervoides: Synthesis and Anti-Diabetic Effects in C57BL/KsJ-db/db Mice[J]. MARINE DRUGS,2013,11(2):350-362. |
| APA | Shi, Dayong.,Guo, Shuju.,Jiang, Bo.,Guo, Chao.,Wang, Tao.,...&Shi, DY.(2013).HPN, a Synthetic Analogue of Bromophenol from Red Alga Rhodomela confervoides: Synthesis and Anti-Diabetic Effects in C57BL/KsJ-db/db Mice.MARINE DRUGS,11(2),350-362. |
| MLA | Shi, Dayong,et al."HPN, a Synthetic Analogue of Bromophenol from Red Alga Rhodomela confervoides: Synthesis and Anti-Diabetic Effects in C57BL/KsJ-db/db Mice".MARINE DRUGS 11.2(2013):350-362. |
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