Discovery Of New Iridoids As Farnesoid X Receptor Agonists From Morinda Officinalis: Agonistic Potentials And Molecular Stimulation

Main observation and conclusionThe 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 mu M, 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 (OST alpha and OST beta). 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.