Isolation and Structural Characterization of Specific Bacterial β-Glucuronidase Inhibitors from Noni (Morinda citrifolia) Fruits

An extract of noni (Morinda citrifolia) fruits has shown potent inhibitory activity on gut bacterial β-glucuronidase, which could help reduce irinotecan-induced diarrhea. In this study, four bacterial β-glucuronidase inhibitors were obtained following bioactive assay-guided isolation, including two sesquineolignans, (7S,8S,7'R,8'R)-isoamericanol B (1) and americanol B (2), and two dineolignans, moricitrins A (3) and B (4). Compounds 2-4 are new, and the absolute configuration of compound 1 was determined for the first time. Their chemical structures were elucidated through HRESIMS and NMR spectra, and their absolute configurations were established via the comparison of the experimental and calculated electronic circular dichroism spectra. These compounds showed potent inhibition against gut bacterial β-glucuronidase with IC50 values in the range 0.62-6.91 μM. The inhibition presented specificity for β-glucuronidase, as all the compounds showed no or weak effects on digestive enzymes such as α-amylase, α-glucosidase, and lipase, suggesting that their gastrointestinal side effects could be minimized. These specific inhibitors as naturally occurring dietary compounds may be developed as promising candidates to alleviate irinotecan-induced diarrhea.