UPLC-ESI-Q-TOF/MS 法在大鼠血浆、胆汁、粪便、尿液和肠道细菌样品中测定原苏木素 B 的代谢产物。

UPLC-ESI-Q-TOF/MS Based Metabolic Profiling of Protosappanin B in Rat Plasma, Bile, Feces, Urine and Intestinal Bacteria Samples.

机构信息

The Second Clinical Medical College, and Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.

State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014, China.

出版信息

Curr Drug Metab. 2021;22(6):491-499. doi: 10.2174/1389200222666210219123846.

DOI:10.2174/1389200222666210219123846

PMID:33605854

Abstract

BACKGROUND

Caesalpinia sappan L. is a traditional medicinal plant that is used to promote blood circulation and treat stroke in China. Protosappanin B (PTB) is a unique homoisoflavone compound isolated from Sappan Lignum (the heartwood of Caesalpinia sappan L). In a previous study, the metabolic fate of PTB remained unknown.

OBJECTIVE

To explore whether PTB is extensively metabolized, the metabolites of PTB in bile, plasma, urine, feces, and intestinal bacteria samples in rats were investigated.

METHODS

The biosamples were investigated by ultraperformance liquid chromatography combined with time-offlight mass spectrometry (UPLC-TOF-MS/MS) with MetabolitePilot software.

RESULTS

28 metabolites were identified in the biosamples: 18 metabolites in rat bile, 8 in plasma, 20 in feces, 7 in urine and 2 in intestinal bacteria samples. Both phase I and phase II metabolites were observed. Metabolite conversion occurred via 9 proposed pathways: sulfate conjugation, glucuronide conjugation, bis-glucuronide conjugation, glucose conjugation, dehydration, oxidation, hydrolysis, methylation and hydroxymethylene loss. The metabolic pathways differed among biosamples and exhibited different distributions. Among these pathways, the most important was sulfate and glucuronide conjugation.

CONCLUSION

The results showed that the small intestinal and biliary routes play an important role in the clearance and excretion of PTB. The main sites of metabolism in the PTB chemical structure were the phenolic hydroxyl and the side-chains on the eight-element ring.

摘要

背景

苏木是一种传统的药用植物，在中国被用来促进血液循环和治疗中风。原苏木素 B（PTB）是从苏木（苏木的心材）中分离出来的一种独特的异黄酮化合物。在之前的研究中，PTB 的代谢物仍不清楚。

目的

为了探讨 PTB 是否广泛代谢，研究了 PTB 在大鼠胆汁、血浆、尿液、粪便和肠道细菌样品中的代谢产物。

方法

采用超高效液相色谱-飞行时间质谱联用（UPLC-TOF-MS/MS）结合MetabolitePilot 软件对生物样品进行分析。

结果

在生物样品中鉴定出 28 种代谢物：18 种在大鼠胆汁中，8 种在血浆中，20 种在粪便中，7 种在尿液中，2 种在肠道细菌样品中。观察到了 I 相和 II 相代谢物。代谢转化通过 9 条提出的途径发生：硫酸盐结合、葡萄糖醛酸结合、双葡萄糖醛酸结合、葡萄糖结合、脱水、氧化、水解、甲基化和羟甲基丢失。代谢途径在生物样品中不同，分布也不同。在这些途径中，最重要的是硫酸盐和葡萄糖醛酸结合。