PTP1B inhibitors from the seeds of Iris sanguinea and their insulin mimetic activities via AMPK and ACC phosphorylation

被引:22
|
作者
Yang, Jun Li [1 ,2 ,3 ]
Thi Kim Quy Ha [1 ]
Lee, Ba Wool [1 ]
Kim, Jinwoong [1 ]
Oh, Won Keun [1 ]
机构
[1] Seoul Natl Univ, Coll Pharm, Res Inst Pharmaceut Sci, Korea Bioact Nat Mat Bank, Seoul 08826, South Korea
[2] Chinese Acad Sci, Lanzhou Inst Chem Phys, CAS Key Lab Chem Northwestern Plant Resources, Lanzhou 730000, Gansu, Peoples R China
[3] Chinese Acad Sci, Lanzhou Inst Chem Phys, Key Lab Nat Med Gansu Prov, Lanzhou 730000, Gansu, Peoples R China
基金
新加坡国家研究基金会;
关键词
Iris sanguinea; Triterpene; PTP1B; AMPK; Glucose uptake; PROTEIN-TYROSINE PHOSPHATASES; TRITERPENOIDS; CONSTITUENTS; SESQUITERPENES; DEFICIENCY; DISCOVERY; FLOWERS; LEAVES;
D O I
10.1016/j.bmcl.2017.09.031
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
To find PTP1B inhibitors from natural products, two new compounds (1 and 2), along with nine known compounds (3-11), were isolated from a methanol-soluble extract of Iris sanguinea seeds. The structures of compounds 1 and 2 were determined based on extensive spectroscopic data analysis including UV, IR, NMR, and MS. The IC50 value of compound 5 on protein tyrosine phosphatase 1B (PTP1B) inhibitory activity is 7.30 +/- 0.88 mu M with a little activity compared to the IC50 values of the tested positive compound. Compound 5 significantly enhanced glucose uptake and activation of pACC, pAMPK and partially Erk1/2 signaling. These results suggest that compound 5 from Iris sanguinea seeds are utilized as both PTP1B inhibitors and regulators of glucose uptake. These beneficial effects could be applied to treat metabolic diseases such as diabetes and obesity. (C) 2017 Elsevier Ltd. All rights reserved.
引用
收藏
页码:5076 / 5081
页数:6
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