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Discovery of New Iridoids as Farnesoid X Receptor Agonists from Morinda officinalis : Agonistic Potentials and Molecular Stimulation
Author(s) -
Luan ZhiLin,
Qiao Fei,
Zhao WenYu,
Ming WenHua,
Yu ZhenLong,
Liu Jie,
Dai ShengYun,
Jiang ShuangHui,
Lian ChaoJie,
Sun ChengPeng,
Zhang BaoJing,
Zheng Jian,
Ma ShuangCheng,
Ma XiaoChi
Publication year - 2021
Publication title -
chinese journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.28
H-Index - 41
eISSN - 1614-7065
pISSN - 1001-604X
DOI - 10.1002/cjoc.202000654
Subject(s) - chemistry , farnesoid x receptor , circular dichroism , agonistic behaviour , stereochemistry , officinalis , biochemistry , nuclear receptor , gene , transcription factor , psychology , psychiatry , aggression , linguistics , philosophy
Main observation and conclusion The investigation of Morinda officinalis led to the isolation of twelve compounds (1—12), including three new iridoid glycosides morindalins 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.