UFLC–MS/MS method for simultaneous determination of six lignans of Schisandra chinensis (Turcz.) Baill. in normal and insomniac rats brain microdialysates and homogenate samples: towards an in‐depth study for its sedative‐hypnotic activity

Abstract

Schisandra chinensis (Turcz.) Baill., a traditional Chinese medicine, has been clinically used for the treatment of insomnia for centuries. The insomnia mechanism and the possible active ingredients of S. chinensis remain largely unknown. The objective of this study was to develop a method to detect its components which could pass through the blood brain barrier (BBB) by determining the brain microdialysate and brain tissue homogenate samples and then obtain the pharmacokinetic profile in brain for comprehensive understanding of its hypnotic clinical efficacy. Therefore, an efficient, sensitive and selective ultra fast liquid chromatography/tandem mass spectrometry method for the simultaneous determination of six sedative and hypnotic lignans (schisandrin, schisandrol B, schisantherin A, deoxyshisandrin, γ-schisandrin and gomisin N) of Schisandra chinensis (Turcz.) Baill. in rat brain tissue homogenate and brain microdialysates has been developed and validated. The analysis was performed on a Shim-pack XR-ODS column (75 mm × 3.0 mm, 2.2 µm) using gradient elution with the mobile phase consisting of acetonitrile and 0.1% formic acid water. The method was validated in brain homogenate and microdialysate samples, which all showed good linearity over a wide concentration range (r(2)> 0.99), and the obtained lower limit of quantification was 0.1 ng · ml(-1) for the analytes in brain microdialysate samples. The intra- and inter-day assay variability was less than 15% for all analytes. The study proved the six lignans, as sedative and hypnotic ingredients, could pass through the BBB with brain targeting, distributed mainly in the hypothalamus and possessed complete pharmacokinetics process in brain. The results also indicated that significant difference in pharmacokinetic parameters of the analytes was observed between two groups, while absorptions of these analytes in insomniac group were significantly better than those in normal group.

In silico Analysis and Experimental Validation of Lignan Extracts from Kadsura longipedunculata for Potential 5-HT1AR Agonists

“…For example, the typical lignan honokiol is able to cross the BBB and the blood-cerebrospinal fluid barrier, and it exerts an anticancer effect [47,48]. Furthermore, six lignans have been detected directly in rat brain tissue after oral administration of lignan extracts [49]. Therefore, the present investigations showed that lignans have the greatest potential for crossing the BBB and modulating the nervous system via a 5-HT1AR agonist-like mechanism.…”

Current knowledge of Schisandra chinensis (Turcz.) Baill. (Chinese magnolia vine) as a medicinal plant species: a review on the bioactive components, pharmacological properties, analytical and biotechnological studies

“…The newest methods applied to determine lignans are: ultra-performance liquid chromatography (UPLC) (Guo et al 2012; Kim et al 2014b; Sun et al 2013b; Yan et al 2014; Zhou et al 2011) and ultra-fast liquid chromatography (UFLC) (Wei et al 2013). Both techniques provide better possibilities than in HPLC but obtained in different ways.…”

Schisandrin C Ameliorates Learning and Memory Deficits by Aβ1-42-induced Oxidative Stress and Neurotoxicity in Mice

“…Blood–brain barrier (BBB) is a main obstacle to the effective delivery of drugs to the brain, which directly impacts on the efficacy of drugs. Previous study showed that the amount of SCH‐C could be detected in rat brain was very low (0.17 ng/mL in brain homogenate) after oral administration (Wei et al ., ). Our view was that compared with the peripheral administration, SCH‐C injected directly into the brain may lead to a better bioavailability and consequently a more potent neuroprotective effect in brain.…”