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

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 EC50 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.