np9b00279_si_001.pdf (5 MB)
Isolation and Structural Characterization of Specific Bacterial β‑Glucuronidase Inhibitors from Noni (Morinda citrifolia) Fruits
journal contribution
posted on 2020-02-21, 20:14 authored by Fei Yang, Wenjun Zhu, Shi Sun, Qing Ai, Paba Edirisuriya, Kequan ZhouAn 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.