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.
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HPN，一种来自红藻红藻的溴苯酚合成类似物：在 C57BL/KsJ-db/db 小鼠中的合成和抗糖尿病作用
DOI：
10.3390/md11020350
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发表时间：
2013-01-30
期刊：
影响因子：
5.4
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Shi D;Guo S;Jiang B;Guo C;Wang T;Zhang L;Li J
3，4-二溴-5-（2-溴-3，4-二羟基-6-（异丙氧基甲基）苄基）苯-1，2-二醇（HPN）是3，4-二溴-5-（2-溴-3，4-二羟基-6-（乙氧甲基）苄基）苯-1，2-二醇（BPN）的合成类似物，从海洋红藻Rhodomela confervoides中分离得到，对蛋白酪氨酸磷酸酶1B（PTP 1B）有较强的抑制作用（IC 50 = 0.84 μmol/L）。体外实验表明，HPN对PTP 1B具有较强的抑制活性，IC 50为0.63 μmol/L，对其它PTPs（T细胞蛋白酪氨酸磷酸酶（TCPTP）、白细胞抗原相关酪氨酸磷酸酶（LAR）、含Src同源2的蛋白酪氨酸磷酸酶-1（SHP-1）和SHP-2）具有较高的选择性。用db/db小鼠模型进行的降血糖实验结果表明，HPN治疗8周后，可显著降低血糖（P < 0.01）。HPN以剂量依赖性方式降低血清甘油三酯和总胆固醇浓度。HPN高、中剂量组均能显著降低HbA 1c水平（P < 0.05）。HPN高剂量组能显著降低胰岛素水平（P < 0.05），但作用不及阳性药罗格列酮。Western blotting结果显示，HPN降低胰腺组织中PTP 1B的水平。最后但并非最不重要的是，Sprague-Dawley大鼠腹腔内葡萄糖耐量试验的结果表明，HPN具有与罗格列酮相似的抗高血糖活性。因此，HPN具有开发为2型糖尿病治疗的潜力。
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 μmol/L). The in vitro assay showed that HPN exhibited enhanced inhibitory activity against PTP1B with IC50 0.63 μmol/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.
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