HPN, a Synthetic Analogue of Bromophenol from Red Alga Rhodomela confervoides: Synthesis and Anti-Diabetic Effects in C57BL/KsJ-db/db Mice

	HPN, a Synthetic Analogue of Bromophenol from Red Alga Rhodomela confervoides: Synthesis and Anti-Diabetic Effects in C57BL/KsJ-db/db Mice
	Shi, Dayong 1,2; Guo, Shuju 1,2; Jiang, Bo 1,2; Guo, Chao 1,2; Wang, Tao 3; Zhang, Luyong 3; Li, Jingya 4
刊名	MARINE DRUGS
	2013-02-01
卷号	11 期号:2 页码:350-362
关键词	bromophenol protein tyrosine phosphatase 1B inhibitor db/db mouse model anti-diabetes properties
ISSN号	1660-3397
通讯作者	Shi, DY
中文摘要	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.
英文摘要	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.
学科主题	Pharmacology & Pharmacy
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Chemistry, Medicinal
研究领域[WOS]	Pharmacology & Pharmacy
关键词[WOS]	TYROSINE-PHOSPHATASE 1B ; PTP1B INHIBITORS ; BIOLOGICAL EVALUATION ; INSULIN SENSITIVITY ; ACID-DERIVATIVES ; DRUGS ; SESQUITERPENES ; DESIGN
收录类别	SCI
原文出处	10.3390/md11020350
语种	英语
WOS记录号	WOS:000315396800005
公开日期	2014-07-17
内容类型	期刊论文
源URL	[http://ir.qdio.ac.cn/handle/337002/16704]
专题	海洋研究所_海洋生物技术研发中心
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
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.,...&Li, Jingya.(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.