Dimeric styrylpyrones with stimulating GLP-1 secretion activities from Alpinia kwangsiensis
文献类型： 外文期刊
作者： Wu, Meng-Zhen 1 ; GongPan, Pian-Chou 2 ; Dai, Meng -Yuan 4 ; Sun, Peng 2 ; Xiao, Chun-Fen 2 ; Li, Jia 1 ; Sun, Yi-Li 3 ; Ji, Kai-Long 2 ;
作者机构： 1.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Jiangsu, Peoples R China
2.Chinese Acad Sci, CAS Key Lab Trop Plant Resources & Sustainable Use, Xishuangbanna Trop Bot Garden, 88 Xuefu Rd, Kunming 650223, Yunnan, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai 201203, Peoples R China
4.Yunnan Acad Agr Sci, Ind Crop Res Inst, Kunming 650223, Yunnan, Peoples R China
5.Bohai Rim Adv Res Inst Drug Discovery, Yantai 264000, Shandong, Peoples R China
关键词： Glucagon-like peptide-1; Type 2 diabetes; Alpinia kwangsiensis; Dimeric styrylpyrones
期刊名称：TETRAHEDRON （ 影响因子：2.388； 五年影响因子：2.134 ）
ISSN： 0040-4020
年卷期： 2022 年 120 卷
页码：
收录情况： SCI
摘要： Stimulating glucagon-like peptide-1 (GLP-1) secretion is an important approach for the treatment of type 2 diabetes. Chemical investigation of Alpinia kwangsiensis rhizomes produced six dimeric styrylpyrones (1-6), including two new degraded ones (1 and 2). Compounds 1-4 were identified as four pairs of enantiomers and successfully prepared by chiral HPLC separation. These compounds incorporate the distinctive cyclobutane moiety via [2 + 2] cycloaddition, a key step in the biosynthetic pathway. The bioactivities of isolates in stimulating GLP-1 secretion in STC-1 cells were evaluated. Results showed that compounds (+)-1, (+)-2, (-)-2, (-)-4, 5 and 6 significantly increased GLP-1 secretion, and compound (+)-1 exhibited the strongest activity with EC50 value of 6.51 mM. In addition, compounds (+)-2, (-)-4 and 5 promoted GLP-1 secretion by increasing intracellular calcium concentration dependent on the PKA pathway, which could provide a chemical basis for the development of diabetes drugs especially that directly promote GLP-1 secretion.
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