Xu Man, Guo Hui, Han Jian, Sun Shi-feng, Liu Ai-hua, Wang Bao-rong, Ma Xiao-chi, Liu Peng, Qiao Xue, Zhang Zi-chuan, Guo De-an
The State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, No. 38 Xueyuan Road, Beijing 100083, PR China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Oct 15;858(1-2):184-98. doi: 10.1016/j.jchromb.2007.08.032. Epub 2007 Aug 30.
This study was conducted to compare the in vivo metabolites of salvianolic acid B (Sal B) between normal rats and antibiotic-treated rats and to clarify the role of intestinal bacteria on the absorption, metabolism and excretion of Sal B. A valid method using LC-MS(n) analysis was established for identification of rat biliary and fecal metabolites. And isolation of normal rat urinary metabolites by repeated column chromatography was applied in this study. Four biliary metabolites and five fecal metabolites in normal rats were identified on the basis of their MS(n) fragmentation patterns. Meanwhile, two normal rat urinary metabolites were firstly identified on the basis of their NMR and MS data. In contrast, no metabolites were detected in antibiotic-treated rat urine and bile, while the prototype of Sal B was found in antibiotic-treated rat feces. The differences of in vivo metabolites between normal rats and antibiotic-treated rats were proposed for the first time. Furthermore, it was indicated that the intestinal bacteria showed an important role on the absorption, metabolism and excretion of Sal B. This investigation provided scientific evidence to infer the active principles responsible for the pharmacological effects of Sal B.
本研究旨在比较正常大鼠和抗生素处理大鼠体内丹酚酸B(Sal B)的代谢产物,并阐明肠道细菌在Sal B吸收、代谢和排泄中的作用。建立了一种使用液相色谱-质谱联用(LC-MS(n))分析的有效方法来鉴定大鼠胆汁和粪便代谢产物。本研究采用反复柱色谱法分离正常大鼠尿液代谢产物。根据正常大鼠胆汁和粪便代谢产物的质谱(MS(n))裂解模式,鉴定出4种胆汁代谢产物和5种粪便代谢产物。同时,根据核磁共振(NMR)和质谱数据首次鉴定出2种正常大鼠尿液代谢产物。相比之下,抗生素处理大鼠的尿液和胆汁中未检测到代谢产物,而在抗生素处理大鼠的粪便中发现了Sal B的原型。首次提出了正常大鼠和抗生素处理大鼠体内代谢产物的差异。此外,研究表明肠道细菌在Sal B的吸收、代谢和排泄中发挥着重要作用。本研究为推断Sal B药理作用的活性成分提供了科学依据。