Wang Qi, Qiao Xue, Qian Yi, Liu Chun-fang, Yang Yan-fang, Ji Shuai, Li Jun, Guo De-an, Ye Min
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Mar 1;983-984:39-46. doi: 10.1016/j.jchromb.2014.12.028. Epub 2015 Jan 12.
Coumarins are an important group of bioactive constituents in licorice (Glycyrrhiza uralensis), a worldwide popular herbal medicine. This study aims to elucidate the metabolism of two major licorice coumarins, glycyrin and glycyrol in rats. After oral administration of 40mg/kg glycyrin, neither the parent compound nor its metabolites could be detected in rats plasma or urine samples, indicating that glycyrin had poor oral bioavailability. Two hydroxylated metabolites, 4″-hydroxyl glycyrin and 5″-hydroxyl glycyrin, were detected in rat liver microsome incubation system. Among them, the major metabolite 4″-hydroxyl glycyrin, which is a new compound, was obtained by microbial transformation of Syncephalastrum racemosum AS 3.264. Its structure was fully identified by 1D and 2D NMR. Meanwhile, glycyrol, together with three metabolites, were detected in rats urine and fecal samples after oral administration (40mg/kg). Their structures were tentatively characterized by LC/MS. Glycyrol mainly undertakes hydroxylation metabolism, accompanied by hydration and dehydrogenation as minor reactions. This is the first systematic study on metabolism of glycyrin and glycyrol. The results could be valuable to evaluate druggability of these bioactive natural products.
香豆素是甘草（Glycyrrhiza uralensis）中一类重要的生物活性成分，甘草是一种在全球广受欢迎的草药。本研究旨在阐明甘草中两种主要香豆素——甘草素和光甘草醇在大鼠体内的代谢情况。口服给予40mg/kg甘草素后，在大鼠血浆或尿液样本中均未检测到母体化合物及其代谢产物，这表明甘草素口服生物利用度较差。在大鼠肝微粒体孵育体系中检测到两种羟基化代谢产物，4″-羟基甘草素和5″-羟基甘草素。其中，主要代谢产物4″-羟基甘草素是一种新化合物，可以通过总状毛霉AS 3.264微生物转化获得，并通过一维和二维核磁共振波谱对其结构进行了全面鉴定。同时，口服给予（40mg/kg）后，在大鼠尿液和粪便样本中检测到光甘草醇及其三种代谢产物，其结构通过液相色谱/质谱进行了初步表征。光甘草醇主要进行羟基化代谢，同时伴有少量的水化和脱氢反应。这是首次对甘草素和光甘草醇代谢进行的系统研究。该结果对于评估这些生物活性天然产物的成药潜力具有重要价值。
