Chemical Constituent of β-Glucuronidase Inhibitors from the Root of Neolitsea acuminatissima.
Neolitsea acuminatissima (Lauraceae) is an endemic plant in Taiwan. One new carboline alkaloid, demethoxydaibucarboline A (1), two new eudesmanolide-type sesquiterpenes, methyl-neolitacumone A (2), neolitacumone E (3), and twelve known compounds (4-15) were isolated from the root of Neolitsea acuminatissima. Their structures were elucidated by spectroscopic analysis. Glucuronidation represents a major metabolism process of detoxification for carcinogens in the liver. However, intestinal bacterial β-Glucuronidase (βG) has been considered pivotal to colorectal carcinogenesis. To develop specific bacterial-βG inhibitors with no effect on human βG, methanolic extract of roots of N. acuminatissima was selected to evaluate their anti-βG activity. Among the isolates, demethoxydaibucarboline A (1) and quercetin (8) showed a strong bacterial βG inhibitory effect with an inhibition ratio of about 80%. Methylneolitacumone A (2) and epicatechin (10) exhibited a moderate or weak inhibitory effect and the enzyme activity was less than 45% and 74%, respectively. These four compounds specifically inhibit bacterial βG but not human βG. Thus, they are expected to be used for the purpose of reducing chemotherapy-induced diarrhea (CID). The results suggest that the constituents of N. acuminatissima have the potential to be used as CID relief candidates. However, further investigation is required to determine their mechanisms of action.
['Lin|Chu-Hung|CH|', 'Chou|Hsiao-Jung|HJ|', 'Chang|Chih-Chi|CC|', 'Chen|Ih-Sheng|IS|', 'Chang|Hsun-Shuo|HS|0000-0003-2745-139X', 'Cheng|Tian-Lu|TL|', 'Kuo|Yueh-Hsiung|YH|0000-0001-5935-6755', 'Ko|Horng-Huey|HH|']
D004353:Drug Evaluation, Preclinical D004791:Enzyme Inhibitors D029968:Escherichia coli Proteins D005966:Glucuronidase D006801:Humans D019770:Lauraceae D015394:Molecular Structure D010936:Plant Extracts D018517:Plant Roots D012717:Sesquiterpenes
β-Glucuronidase root Neolitsea acuminatissima Lauraceae carboline chemotherapy-induced diarrhea (CID) eudesmanolide