Yang Fei, Zhu Wenjun, Sun Shi, Ai Qing, Edirisuriya Paba, Zhou Kequan
Department of Nutrition and Food Science, Wayne State University, Detroit, Michigan 48202, United States.
J Nat Prod. 2020 Apr 24;83(4):825-833. doi: 10.1021/acs.jnatprod.9b00279. Epub 2020 Feb 21.
An extract of noni () 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, (7,8,7',8')-isoamericanol B () and americanol B (), and two dineolignans, moricitrins A () and B (). Compounds - are new, and the absolute configuration of compound 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 IC 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.
诺丽果提取物对肠道细菌β-葡萄糖醛酸酶具有显著的抑制活性，这可能有助于减轻伊立替康引起的腹泻。在本研究中，通过生物活性测定指导的分离获得了四种细菌β-葡萄糖醛酸酶抑制剂，包括两种倍半木脂素，（7,8,7',8'）-异美登醇B和美登醇B，以及两种双木脂素，桑橙素A和B。化合物-是新的，并且首次确定了化合物的绝对构型。通过高分辨电喷雾电离质谱（HRESIMS）和核磁共振（NMR）光谱阐明了它们的化学结构，并通过比较实验和计算的电子圆二色光谱确定了它们的绝对构型。这些化合物对肠道细菌β-葡萄糖醛酸酶表现出显著的抑制作用，IC值在0.62-6.91μM范围内。这种抑制作用对β-葡萄糖醛酸酶具有特异性，因为所有化合物对α-淀粉酶、α-葡萄糖苷酶和脂肪酶等消化酶均无作用或作用较弱，这表明它们的胃肠道副作用可能会降至最低。这些作为天然膳食化合物的特异性抑制剂可能会被开发成为减轻伊立替康引起腹泻的有前景的候选药物。
