Discovery of New Iridoids as Farnesoid X Receptor Agonists from Morinda officinalis: Agonistic Potentials and Molecular Stimulation  

作　　者：Zhi-Lin Luan Fei Qiao Wen-Yu Zhao Wen-Hua Ming Zhen-Long Yu Jie Liu Sheng-Yun Dai Shuang-Hui Jiang Chao-Jie Lian Cheng-Peng Sun Bao-Jing Zhang Jian Zheng Shuang-Cheng Ma Xiao-Chi Ma 

机构地区：[1]Dalian Key Laboratory of Metabolic Target Characterization and Traditional Chinese Medicine Intervention,College of Pharmacy,College of Integrative Medicine,Dalian Medical University,Dalian,Liaoning 116044,China [2]National Institutes for Food and Drug Control,Beijing 102629,China

出　　处：《Chinese Journal of Chemistry》2021年第5期1288-1296,共9页中国化学（英文版）

基　　金：the National Natural Science Foundation of China(No.81703679);the Liaoning Provincial Key Research and Development Program(No.2019JH2/10300022);the Natural Science Foundation of Liaoning Province(No.2020-MS-256);the Dalian Young Star of Science and Tech nology(Nos.2019RQ123 and 2019RQ116).

摘　　要：The investigation of Morinda officinalis led to the isolation of twelve compounds(1-12),including three new iridoid glycosides morindallns A-C(1-3)and nine known compounds(4-12).Their structural identifications were conducted using HRMS,1D and 2D NMR,and electronic circular dichroism(ECD)spectra as well as quantum chemical computations.Compound 6 displayed the most significantly agonistic activity against farnesoid X receptor(FXR)with an EC_(50) value of 7.18 μM,and its agonistic effect was verified through the investigation of FXR downstream target genes including small heterodimer partner 1(SHP1),bile salt export pump(BSEP),and organic solute transporter subunit alpha and beta(OSTα and OSTβ).The potential interaction of compound 6 with FXR was analyzed by molecular docking and molecular dynamics stimulation,revealing that amino acid residues Leu287;Thr288,and Ser332 played a crucial role in the activation of compound 6 towards FXR.These findings suggested that compound 6 could be regarded as a potential candidate for the development of FXR agonists.

关 键 词：Morinda officinalis IRIDOID Farnesoid X receptor Agonistic effect 

分 类 号：O62[理学—有机化学]