Pharmacokinetic comparisons of schizandrin after oral administration of schizandrin monomer, Fructus Schisandrae aqueous extract and Sheng-Mai-San to rats

Abstract

Sheng-Mai-San (SMS) is a famous traditional Chinese medicine (TCM) recipe, containing Radix Ginseng (Panax ginseng C.A. Mey., Araliaceae), Radix Ophiopogonis (Ophiopogon japonicus (Thunb.) Ker-Gawl., Liliaceae) and Fructus Schisandrae (Schisandra chinensis (Turcz.) Baill., Magnoliaceae), and has been used more than one thousand years. In this research, pharmacokinetics of one component of this TCM recipe was studied. Schizandrin is the main absorbed effective ingredient of Fructus Schisandrae and its pharmacokinetics were studied following oral administration of pure schizandrin, Fructus Schisandrae aqueous extract, and SMS decoction in rats with approximately the same dose of 5 mg/kg. At different time points (0, 0.083, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 h) after administration, the concentrations of schizandrin in rat plasma were determined by LC–MS, and main pharmacokinetic parameters were estimated. It was found that both AUC_0-tn and T_1/2 of schizandrin in Fructus Schisandrae aqueous extract and in SMS decoction were increased significantly (p < 0.05) comparing with that in monomer. The content assay also revealed that the concentrations of lignans would increase when SMS decocting, comparing with Fructus Schisandrae. These results indicate that some ingredients in SMS may increase the dissolution of schizandrin when decocting in vitro, and delay its elimination and enhance its bioavailability in rat.

Introduction

Traditional Chinese medicine (TCM), which uses natural therapeutic agents under the guidance of the theory of traditional Chinese medical science and has been applied by TCM practitioners for years, attracts extra attention in recent years. Studies on standardizations of compound prescriptions are essential, and pharmacokinetics is usually considered as one of the limited points in this process. Because of the complexity of chemicals and unknown effective ingredients in compound prescriptions, pharmacokinetic studies of TCM are faced with many difficulties. However, there were more and more reports on that appeared lately. Most of the published reports selected one or several representative compounds as the targets to investigate the pharmacokinetics of the whole prescription (Rath et al., 2004, Liao et al., 2005) and elucidate the mechanism of compatibility of compound recipe through pharmacokinetic processes. Several papers focused on how the individual component in the compound prescription interact with other ingredients (Zuo et al., 2003, Bochu et al., 2005, Di et al., 2006, Lu et al., 2007).

Sheng-Mai-San (SMS), a traditional Chinese formula containing Radix Ginseng (Panax ginseng C.A. Mey., Araliaceae), Radix Ophiopogonis (Ophiopogon japonicus (Thunb.) Ker-Gawl., Liliaceae) and Fructus Schisandrae (Schisandra chinensis (Turcz.) Baill., Magnoliaceae), is officially recorded in Chinese Pharmacopoeia (State Pharmacopoeia Committee, 2005). It has long been used for the treatment of loss of essence-energy and excessive body fluid, and is especially prescribed for coronary artery disease in China (Wang et al., 2002). Fructus Schisandrae is called in mandarin “wu-wei-zi”, in Japanese “Gomishi” and in Korean “Omicha”. It is always used as an antihepatotoxic, antioxidative, detoxical, antiasthmatic, anticarcinogenic, antidiabetic, sedative and tonic agent, and lignans are usually considered as the main pharmacological effective compounds (Wagner and Bauer, 1996, Hancke et al., 1999) in it. Among them, schizandrin has been used as a phytochemical marker for the quality control of Fructus Schisandrae in Chinese Pharmacopoeia.

Pharmacokinetic studies on lignans, such as schizandrin (Cui and Wang, 1992, Ikeya et al., 1995, Ono et al., 1995, Xu et al., 2005, Xu et al., 2007), γ-schizandrin (Gu et al., 2001, Wang et al., 2004a, Wang et al., 2004b) and gomisin A (Matsuzaki et al., 1991) in some prescriptions, have been carried out. However, the pharmacokinetic influence of other herbs on them in Fructus Schisandrae (herb–herb interaction) was seldom reported. The pharmacokinetic effect of the combination with Radix Salvia Miltiorrhizae (Salvia miltiorrhiza Bge., Labiate) on lignans (Wang et al., 2004a, Wang et al., 2004b) was studied and the result indicated that metabolic rates of schizandrin and γ-schizandrin in mouse were lower than that of non-combination. The aim of this research is to study the possible pharmacokinetic differences of the compounds after oral administration of monomer, Fructus Schisandrae aqueous extract and SMS decoction to rats and explore whether there are some herb-herb interactions on lignans in SMS by determining the absorbed lignans in SMS decoction.