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

Abstract

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 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 (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.

Physiological and transcriptomic analysis reveals the potential mechanism of Morinda officinalis How in response to freezing stress

“…The roots of MO have been often used as a tonic or traditional Chinese medicine attributed to its unique effects of tonifying kidney-yang, strengthening muscles and bones, and eliminating wind dampness [ 1 ]. Researches showed that MO contained many bioactive components, such as oligosaccharides, polysaccharides, iridoids and anthraquinones [ 2 – 5 ]. Among them, nystose of the oligosaccharide component had attracted extensive attention owing to its high content, anti-depression and anti-osteoporosis effects [ 6 – 8 ].…”