Pharmacokinetic interaction among co-existing herbal ingredients
leading to high plasma concentrations of Z-butylidenephthalide, a
minor ingredient in Rhizoma Chuanxiong, in rat.
Running title: Pharmacokinetics of Z-butylidenephthalide in rat
Keywords: Z-butylidenephthalide; Rhizoma Chuanxiong; pharmacokinetics; first-pass
metabolism; hydration; ligustilide; interaction
Pharmacokinetic interaction among co-existing herbal ingredients leading to high
plasma concentrations of Z-butylidenephthalide, a minor ingredient in Rhizoma
Chuanxiong, in rat.
Ru Yan1, 2, Nga Ling Ko1, Bin Ma1, Yun Kau Tam3 and Ge Lin1*
1
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong
Kong, Shatin, N.T., Hong Kong, SAR; 2Institute of Chinese Medical Sciences, University
of Macau, Taipa, Macau, SAR; 3Sinoveda Canada Inc., Edmonton, Alberta, Canada
Abstract
Pharmacokinetics (PK) study of herbal medicines is a great challenge, because which
component(s) is(are) the bioactive ingredients in individual herbs is largely unknown.
Most of the reported PK studies of herbal medicines were conducted on the major
ingredients regardless of their activities. However, PK of components with low content
in herbs is often ignored. The present study investigated PK of Z-butylidenephthalide
(BuPh), a bioactive phthalide present in a significantly low quantity in Rhizoma
Chuanxiong, a medicinal herb widely prescribed for the treatment of cardiovascular
disorders. PK of BuPh was investigated in rats using Chuanxiong extract, a fraction
containing BuPh and ligustilide, a major bioactive phthalide in the herb, and pure BuPh,
respectively. The results demonstrated that BuPh exhibited rapid intestinal absorption,
wide distribution and quick elimination with a low oral bioavailability (16-19%) due to
extensive first-pass metabolism. Interestingly, AUC of BuPh via intake of the fraction
(9-fold) and the extract (4-fold) was significantly greater than that obtained fro pure
BuPh, which was evidenced to be due to metabolic conversion from ligustilide. Our
findings demonstrated that although naturally presented in low amount BuPh reached
significant systemic concentrations by PK interaction via metabolic convention from
ligustilide, a major component in the herb. Therefore, study of herbal medicines should
be more appropriate to focus on in vivo profile of the ingredients co-existed in herbs.