Pharmacokinetics, tissue distribution and metabolism of senkyunolide I, a major bioactive component in Ligusticum chuanxiong Hort. (Umbelliferae).
BACKGROUND
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.


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.
Engineering Research Center of Modern Preparation Technology of TCM, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China.
Chun-Yong
CY
He
Shuo
S
Wang
Yi
Y
Feng
Shuang
S
Liang
Xiao
X
Lin
De-Sheng
DS
Xu
Ke-Feng
KF
Ruan
D000818:Animals; D001572:Benzofurans / Q000097:blood / Q000493:pharmacokinetics*; D001646:Bile / Q000737:chemistry; D030004:Ligusticum; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D001572:Benzofurans; C576743:senkyunolide I