川芎(伞形科)中的一种主要生物活性成分——洋川芎内酯Ⅰ的药代动力学、组织分布和代谢

Engineering Research Center of Modern Preparation Technology of TCM, Ministry of Education, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China

Ethnopharmacological relevance: Ligusticum chuanxiong Hort. (Umbelliferae) is widely prescribed for treatment of cardiovascular diseases in China for centuries. One of the major bioactive components in L. chuanxiong is senkyunolide I (SEI), which shows pharmacological activities in anti-migraine and anti-oxidative damage. Materials and methods: The aim of this study was to investigate in vivo pharmacokinetics, tissue distribution and metabolism of SEI in rats. The concentrations of SEI in plasma and tissues were determined by a high performance liquid chromatography (HPLC) method, and the pharmacokinetic parameters were calculated using and non-compartmental analysis. The metabolites were identified using high performance liquid chromatography tandem mass (HPLC-ESI-MS/MS) method. Results: After oral and intravenous administration, SEI was quickly eliminated from plasma and its oral bioavailability (BA) was about 37.25%, which was smaller than intraportal BA (81.17%), but similar to intraduodenal BA (36.91%), suggesting that gastric first-pass effect of SEI is negligible, and hepatic first-pass effect was approximately 18.83%. After oral administration, SEI could penetrate blood brain barrier and extensively distribute in tested tissues, with the descending order of AUC being kidney, liver, lung, muscle, brain, heart, thymus, and spleen in rat. The parent compound and nine metabolites were found and identified in rat bile after oral administration of SEI (36 mg/kg). The metabolic mechanism of SEI in rat mainly involves methylation, glucuronidation and glutathione conjugation during the phase II biotransformation pathway in rats. Conclusions: The information gained here may provide a meaningful basis for clinical application of such a bioactive compound of herbal medicines. © 2012 Elsevier Ireland Ltd.

Feng, Y.; Engineering Research Center of Modern Preparation Technology of TCM, Ministry of Education, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China; email: fyi@vip.sina.com