Pharmacokinetics of Schizandrin and Its Pharmaceutical Products Assessed Using a Validated LC–MS/MS Method

Abstract

Schisandra chinensis has been used as an important component in various prescriptions in traditional Chinese medicine and, more recently, in Western-based medicine for its anti-hepatotoxic effect. The aim of this study was to develop a selective, rapid, and sensitive ultra-performance liquid chromatography-tandem mass spectrometry method for pharmacokinetic studies of schizandrin in rats. Liquid-liquid extraction was used for plasma sample preparation. A UHPLC reverse-phase C18e column (100 mm × 2.1 mm, 2 μm) coupled with a mobile phase of methanol-0.1% formic acid (85:15, v/v) was used for sample separation. A triple quadrupole tandem mass spectrometer was used to detect the analytes in the selected reaction monitoring mode. The linear range of schizandrin in rat plasma was 5.0–1000 ng/mL (r2 > 0.999), with a lower limit of quantification of 5 ng/mL. The method was validated with regard to accuracy, intra-day and inter-day precision, linearity, stability, recovery, and matrix effects in rat plasma, which were acceptable according to the biological method validation guidelines developed by the FDA. This method was successfully applied to a pharmacokinetic study after oral administration of 3 g/kg and 10 g/kg of Schisandra chinensis products, which yielded a maximum concentration of schizandrin of 0.08 ± 0.07 and 0.15 ± 0.09 μg/mL, respectively. A parallel study design was used to investigate the oral bioavailability of single compound of schizandrin and the herbal extract, the single compound of pure schizandrin (10 mg/kg, i.v.), pure schizandrin (10 mg/kg, p.o.), and the herbal extract of Schisandra chinensis (3 g/kg and 10 g/kg, p.o.) were given individually. The dose of Schisandra chinensis (3 g/kg) equivalent to schizandrin (5.2 mg/kg); the dose of Schisandra chinensis (10 g/kg) equivalent to schizandrin (17.3 mg/kg). The result demonstrated that the oral bioavailability of schizandrin was approximately 15.56 ± 10.47% in rats, however the oral bioavailability of herbal extract was higher than single compound. The method was successfully applied to the pharmacokinetic study of pure schizandrin after oral administration of its pharmaceutical industry products in rats.

Assaying Chlamydia pneumoniae persistence in monocyte-derived macrophages identifies schisandrin lignans as phenotypic switchers

“…To date, only a few drug-like molecules have been described as phenotypic switchers reverting persister bacteria from dormancy to active growth 2, 54, 55 and to our knowledge, the schisandrin lignans represent the first phenotypic switchers described to be active on intracellular bacteria. Based on rodent bioavailability studies, micromolar plasma concentrations of the lignans can be achieved after a single oral dose 56 , indicating the potential of the lignans as leads for orally administered drugs. Furthermore, our in vitro cell viability data (Supplementary information, 29, 42 and the numerous in vivo studies on these compounds 45 indicate the lack of acute or subacute toxicity of the lignans.…”

Assaying Chlamydia pneumoniae Persistence in Monocyte-Derived Macrophages Identifies Dibenzocyclooctadiene Lignans as Phenotypic Switchers

“…To date, only a few drug-like molecules have been described as phenotypic switchers reverting persister bacteria from dormancy to active growth [4,26,27] and to our knowledge, the schisandrin lignans represent the first phenotypic switchers described to be active on intracellular bacteria. Based on rodent bioavailability studies, micromolar plasma concentrations of the lignans can be achieved after a single oral dose [28], indicating the potential of the lignans as scaffolds for orally administered drugs. Furthermore, our in vitro cell viability data (Table 2) and the numerous in vivo studies on these compounds [29] indicate the lack of acute or subacute toxicity of the lignans.…”

Antioxidant Effects of Schisandra chinensis Fruits and Their Active Constituents

“…The bioavailability studies of S. chinensis products were mainly performed in animals. A maximum concentration of schisandrin of 0.08 ± 0.07 and 0.15 ± 0.09 μg/mL was achieved after oral administration of 3 g/kg and 10 g/kg of S. chinensis fruit extract in rats [ 15 ]. In a parallel study, schisandrin (10 mg/kg, administered intravenously (i.v.)…”

“…and the herbal extract of S. chinensis (3 g/kg and 10 g/kg, p.o.) were given indivi-dually to rats [ 15 ]. The dose of S. chinensis (3 g/kg) was equivalent to schisandrin (5.2 mg/kg), whereas the dose of S. chinensis (10 g/kg) was equivalent to schisandrin (17.3 mg/kg) [ 15 ].…”