Schisandra Chinensis Baill Research Articles

Anti-inflammatory effects of chicanine on murine macrophage by down-regulating LPS-induced inflammatory cytokines in IκBα/MAPK/ERK signaling pathways

Schisandra chinensis Baill is a Chinese traditional medicine with multiple pharmacological activities. In this study, chicanine, one of the major lignan compounds of S. chinesis, was investigated for suppressive effects on lipopolysaccharide (LPS)-induced inflammatory responses in murine macrophages (RAW 264.7 cells). Chicanine was found to have anti-inflammatory properties with the inhibition of nitric oxide (NO) and Prostaglandin E (2) (PGE2) production and nuclear factor-κB (NF-κB) signaling in LPS-stimulated RAW 264.7 cells with no cytotoxic effects. Treatment of RAW 264.7 cells with chicanine down-regulated LPS-induced expression of pro-inflammatory cytokines including TNFα, IL-1β, MCP-1, G-CSF, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). These inhibitory effects were found with the blockage of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases 1 and 2 (ERK 1/2), and also IκB-α phosphorylation. These results indicated that anti-inflammatory actions of chicanine in macrophages involved inhibition of LPS-induced TLR4-IκBα/MAPK/ERK signaling pathways.

<i>Schisandra Chinensis</i> baill, a chinese medicinal herb, alleviates high-fat-diet-inducing non-alcoholic steatohepatitis in rats

he present study aims to explore whether Schisandra chinensis Baill, a Chinese, medicinal herb can alleviates high-fat-diet-inducing non-alcoholic steatohepatitis in rats. In the study, 24, male Wister rats with body weight between 180-220g, were included. The rats were randomly divided into four groups: model group, normal control group, rosiglitazone group, and Schisandra chinensis Baill group. The treatment lasted for 56, days. The high-fat diet used in the present study includes 25% lard, 2%, cholesterol 0.5%, sodium cholate, and 25%, Tween-80. The hepatic levels of superoxide dismutase (SOD), and malondialdehyde (MDA); the serum levels of total cholesterol (TC), and low-density lipoprotein cholesterol (LDLC), were detected. We found that the hepatic levels of SOD were significantly lower, and the serum levels of TC, LDLC as well as, the hepatic levels of MDA in model group were significantly higher than those of normal control group; rosiglitazone group and Schisandra chinensis Baill group (P<0.05), indicates that non-alcoholic steatohepatitis rats were successfully induced by high-fat diet. Schisandra chinensis Baill group presented a significant lower serum levels of LDLC, than rosiglitazone group (P<0.05); and the hepatic levels of SOD in Schisandra chinensis Baill group were significantly lower than rosiglitazone group (P<0.05). However, no significant difference existed between Schisandra chinensis Baill group, and rosiglitazone group on the hepatic levels of MDA and the serum levels of TC (P>0.05). It is then concluded that Schisandra chinensis Baill can significantly alleviate the non-alcoholic steatohepatitis of the rats induced by high-fat diet, and it may be used as a complementary therapy for rosiglitazone.

Profiling and identification of the absorbed constituents and metabolites of schisandra lignans by ultra‐performance liquid chromatography coupled to mass spectrometry

Schisandra chinensis Baill grows wild in Russia, China, Korea and Japan, and its fruit has been found to be effective in amnesia and insomnia. It is enriched in schisandra lignans (SL) that are major components responsible for therapeutic action. However, there are no reports on the biotransformation analysis of SL. An ultra-performance liquid chromatography/electrospray-ionization high-definition mass spectrometry (UPLC-Q-TOF-HDMS) method was developed to investigate the metabolism of SL in vivo. MS was performed on a Waters Micromass high-definition system with an electrospray ionization source in positive ion mode and automated MetaboLynx software analysis with excellent MS accuracy and enhanced MS data acquisition. An improved mass defect filter (MDF) method employing both drug and core structure filter templates was applied to the processing of UPLC-Q-TOF-HDMS data for the detection and structural characterization of metabolites. In this study, 30 metabolites were detected and identified in vivo, and demethylation and hydroxylation were confirmed as the primacy metabolic pathway for SL in rat plasma. In conclusion, the presently developed methodology was suitable for biotransformation research of SL and will find wide use in metabolic studies for other herbal medicines.

Hollow fiber cell fishing with high performance liquid chromatography for screening bioactive compounds from traditional Chinese medicines

A novel hollow fiber cell fishing method with high performance liquid chromatography was proposed and used to screen, isolate, and analyze bioactive compounds from Traditional Chinese Medicines (TCMs). The active compounds that interact with the living cells acceptor inside the hollow fiber lumen were screened and isolated from the TCM extracts in phosphate buffer solution (pH 7.4). Subsequently, the active compounds bound to the cells were desorbed with methanol, and were analyzed using HPLC. HFCF with HPLC was introduced for the screening and analysis of lignans in Schisandra chinensis (Turcz) Baill and coumarins in Fructus Cnidii and Fructus Psoraleae. The surface properties of the hollow fibers filled with living cells were characterized. The nonspecific binding between the active centers of the hollow fibers and the bioactive compounds were investigated. The cell survival rates were determined before and after the screening. The repeatability of the method was tested. Some structures of the lignans and coumarins screened from TCMs were identified by the comparison to the retention times of the reference substances. HFCF-HPLC is a simple, fast, effective, and reliable method for the screening and analysis of bioactive compounds, and it can be extended to screen other bioactive compounds from TCMs.

Aqueous two-phase system coupled with ultrasound for the extraction of lignans from seeds of Schisandra chinensis (turcz.) Baill

Total lignans were extracted using an aqueous two-phase system combined with an ultrasound-assisted extraction method from Schisandra chinensis Baill (SCB) seeds. The three main functional components, schizandrin (SA), schisantherin A (SAA) and deoxyschizandrin (DSA), were selected as markers. Initially, the phase separation ability of various salts and ethanol were compared, then response surface methodology (RSM) experiments were used to investigate the effects of extraction time, ultrasound power and solvent to solid ratio on extraction efficiency. The partition coefficient and recovery of three markers indicated that a system based on ethanol and (NH4)2SO4 was the best system. The optimal phase composition was 25% (w/w) (NH4)2SO4 and 19% (w/w) ethanol, and the partition coefficients of SA, SAA and DSA were 77.09, 76.73 and 86.99, respectively, with a recovery of >93%. The optimal conditions for total lignan extraction was selected as 20:1 (solvent:solid), 800W and 61.1min, which resulted in yields for SA, SAA and DSA of 13.10, 1.87 and 1.84mg/g, respectively. Compared with an 80% ethanol (v/v) extraction method, this method has the advantages of combining extraction with purification in a single step and yields higher purity total lignans from the seeds of SCB.

Response Surface Modeling and Optimization of Accelerated Solvent Extraction of Four Lignans from Fructus Schisandrae

A new method based on accelerated solvent extraction (ASE) combined with response surface methodology (RSM) modeling and optimization has been developed for the extraction of four lignans in Fructus Schisandrae (the fruits of Schisandra chinensis Baill). The RSM method, based on a three level and three variable Box-Behnken design (BBD), was employed to obtain the optimal combination of extraction condition. In brief, the lignans schizandrin, schisandrol B, deoxyschizandrin and schisandrin B were optimally extracted with 87% ethanol as extraction solvent, extraction temperature of 160 °C, static extraction time of 10 min, extraction pressure of 1,500 psi, flush volume of 60% and one extraction cycle. The 3D response surface plot and the contour plot derived from the mathematical models were applied to determine the optimal conditions. Under the above conditions, the experimental value of four lignans was 14.72 mg/g, which is in close agreement with the value predicted by the model.

A new approach to catalytic hydrolysis of ester-bound biphenyl cyclooctene lignans from the fruit of Schisandra chinensis Baill by ion exchange resin

In this study, a novel approach was developed to hydrolyze ester-bound biphenyl cyclooctene lignans (EBBCL) from the fruits of Schisandra chinensis Baill into free-state biphenyl cyclooctene lignans (FSBCL) using ion exchange resin. The results of static hydrolysis tests showed that SK1B (H-type strongly acidic cation exchange resin) was the best acidic hydrolysis catalyst and 201×7 (OH-type strongly basic anion exchange resin) was the best basic hydrolysis catalyst. According to the underlying mechanism for hydrolytic degradation, the hydrolysis effect of basic catalyst is more obviously. The dynamic hydrolysis efficiency of 201×7 (146.7±5.0%) was higher than that of SK1B (131.5±4.7%). Compared with the purity of FSBCL (3.52±0.06%) catalytic hydrolysis by traditional catalyst NaOH, the purity of FSBCL (5.85±0.04%) hydrolysis by 201×7 resin was much higher, increased 2.94-fold under the optimization hydrolysis conditions.

Ionic liquid-based microwave-assisted extraction of essential oil and biphenyl cyclooctene lignans from Schisandra chinensis Baill fruits

Ionic liquid-based microwave-assisted extraction (ILMAE) has been successfully applied in extracting essential oil and four kinds of biphenyl cyclooctene lignans from Schisandra chinensis Baill. 0.25 M 1-lauryl-3-methylimidazolium bromide ionic liquid is selected as solvent. The optimum parameters of dealing with 25.0 g sample are 385 W irradiation power, 40 min microwave extraction time and 1:12 solid-liquid ratio. The yields of essential oil and lignans are 12.12±0.37 ml/kg and 250.2±38.2 mg/kg under the optimum conditions. The composition of the essential oil extracted by hydro-distillation, steam-distillation and ILMAE is analyzed by GC-MS. With ILMAE method, the energy consumption time has not only been shortened to 40 min (hydro-distillation 3.0 h for extracting essential oil and reflux extraction 4.0 h for extracting lignans, respectively), but also the extraction efficiency has been improved (extraction of lignans and distillation of essential oil at the same time) and reduces the environmental pollution. S. chinensis materials treated by different methods are observed by scanning electronic microscopy. Micrographs provide more evidence to prove that ILMAE is a better and faster method. The experimental results also indicate that ILMAE is a simple and efficient technique for sample preparation.

Study on ionic liquid-based ultrasonic-assisted extraction of biphenyl cyclooctene lignans from the fruit of Schisandra chinensis Baill

The ionic liquid-based ultrasonic-assisted extraction (ILUAE) has been successfully applied in extracting four biphenyl cyclooctene lignans from the fruit of Schisandra chinensis Baill. Seventeen different types of ionic liquids with different cations and anions have been investigated. 0.8 M 1-lauryl-3-methylimidazolium bromide ([C12mim]Br) solution was selected as solvent. In addition, the ultrasonic parameters including ultrasonic power, time for ultrasonic treatment and solid–liquid ratio have been optimized by Response Surface Method (RSM). Compared with the conventional solvent extraction, the efficiency of the approach proposed in this work is about 3.5 times as much as that of the conventional solvent extraction method. With the proposed extraction method, the extraction time has been reduced to 30 min, whereas the conventional extraction method requires about 6.0 h. The experimental results presented in this work indicate that the ILUAE is a simple and efficient technique for sample preparation. The proposed method is reproducible.

Non-thermal extraction of effective ingredients from Schisandra chinensis Baill and the antioxidant activity of its extract

Schisandra chinensis (Turcz.) Baill has been used as a traditional Chinese medicine in China and Japan. It has been used as an anti-aging drug, a stimulant, a sedative and a tonic drug. Its active components are lignans, including deoxyschisandrin, γ-schisandrin, schizandrin, gomisin A, and so on. Both deoxyschisandrin and γ-schisandrin were proved to have the effect of protection against CCl4-induced hepatic damage. The extraction of deoxyschisandrin and γ-schisandrin from S. chinensis using classical methods, however, are tedious and time consuming. So, ultrahigh pressure extraction (UHPE) was used to extract deoxyschisandrin and γ-schisandrin from S. chinensis. At the same time, heat reflux and ultrasonic extraction methods were chosen as the comparative methods. UHPE optimum extraction conditions were as follows: 400 MPa pressure, 90% ethanol–water solution, 90 : 1 liquid : solid ratio, 5 min extraction time; the extraction yields of deoxyschisandrin and γ-schisandrin were 0.3132 and 0.0612%. The extraction yields of deoxyschisandrin and γ-schisandrin with heat reflux and ultrasonic extraction methods were 0.280 and 0.0483%, 0.272 and 0.0505%, and the extraction times were 2 h and 20 min, respectively. UHPE had the highest extraction yields with the shortest extraction time of the three extraction methods. Furthermore, the UHPE extract had the highest antioxidant activity. So UHPE can not only shorten the extraction time, but also mostly protect the extracts' bioactivities. In a word, UHPE is an efficient extraction method for the extraction of effective ingredients from S. chinensis.

Induction of the Phase II Detoxification Enzyme NQO1 in Hepatocarcinoma Cells by Lignans from the Fruit ofSchisandra chinensisthrough Nuclear Accumulation of Nrf2

The upregulation of phase II detoxification genes is believed to play an important role in cancer prevention. The molecular mechanism underlying the changes in gene expression that accompany cancer prevention involves activation of the transcription factor, NF-E2-related factor 2 (Nrf2). In traditional medicine, the fruit of Schisandra chinensis Baill is used as a tonic, an anti-tussive and an anti-aging drug. In the current study, nine lignans were isolated from S. chinensis and tested for their ability to induce quinone reductase (QR) activity in Hepa1c1c7 mouse hepatocarcinoma cells. Tigloylgomisin H (TGH) and angeloylgomisin H (AGH) significantly induced QR activity and exhibited a relatively high chemoprevention index (CI) (10.80 and 4.59, respectively) as compared to control. TGH also induced QR activity in BPrc1 mouse hepatocarcinoma cells as well, which are defective in aryl hydrocarbon nuclear translocator (Arnt). In HepG2 human hepatocarcinoma cells, TGH significantly activated gene expression mediated by the antioxidant response element (ARE), a key regulatory region in the promoters of detoxification enzymes, through the nuclear accumulation of Nrf2. The results of the current study suggest that TGH functions as a novel monofunctional inducer that specifically upregulates phase II enzymes through the Nrf2-ARE pathway. TGH thus represents a potential liver cancer prevention agent.

Resolution of Two-Way Chromatographic Data of Schisandra chinensis Baill. Using a Modified Slice-Scan Method for Direct Determination of the Components in Overlapping Peaks

Slice-scan method (SS) scans the two-way chromatographic data at each retention time point, and hence obtains the corresponding spectral "slice"s. Then, the spectral slices are transformed into new spectral profiles by spectral transformation, based on which qualitative and quantitative analysis of the overlapping chromatographic peaks could be done. In this work, a new strategy for directly determining the component of interest in the overlapping chromatographic peak is presented, which takes advantage of the selective spectral slices of the determined component and establishes the best calibration curve by applying the new generated spectral profiles after spectral transformation. Meanwhile, the contents of four bioactive lignans, schisandrin, schisantherin, deoxyschizandrin and gamma-schizandrin in Schisandra chinensis Baill., a famous herb in China were determined using SS together with the new quantitative strategy, and satisfactory results have been obtained.

Effects of schisandrin on transcriptional factors in lipopolysaccharide-pretreated macrophages

Schisandrin is the main active ingredient isolated from Schisandra chinensis Baill. Recent studies have demonstrated that schisandrin exhibits anti-inflammatory effects in vivo and in vitro. In this study, we examined whether the order of lipopolysaccharide (LPS) treatment affects the mechanism of schisandrin anti-inflammatory activity. We found that the antiinflammatory mechanisms are not the same depending on whether macrophages were treated with schisandrin before or after LPS. The main difference is that inhibitor kappaBalpha (IkappaBalpha) degradation was not inhibited when macrophages were pretreated by LPS before schisandrin and was weakly inhibited when macrophages were pretreated by schisandrin before LPS.

Anti-inflammatory effects of schisandrin on modulation of NF-κB, JNK and p38 MAP kinases

Schisandrin is the main active lignan isolated from Schisandra chinensis Baill. (Schisandraceae). Recent studies have demonstrated that schisandrin exhibits anti-inflammatory effects in vivo and in vitro [1]. In this study, we found that the anti-inflammatory mechanisms are not totally the same according to whether macrophages are pretreated with schisandrin before LPS (Lipopolysaccharide) or not. Schisandrin (50µM) increased the activation of JNK and p38 by transient stimulation of LPS and decreased the activation of those two by persistent stimulation of LPS. Moreover, schisandrin (50 and 100µM) inhibited the activation of NF-κB. These results suggest that schisandrin might be involved in anti-proliferation of cells. The data also demonstrate that schisandrin inhibits proliferation of A549 cancer cells through modulating p38 and JNK activation and reducing ERK activation [2] http://www.ncbi.nlm.nih.gov/sites/entrez? Db=pubmed&amp;Cmd=Search&amp;Term=%22Ip SP%22%5B Author%5D&amp;itool=EntrezSystem2. PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus.

Anti-inflammatory effects of schisandrin isolated from the fruit of Schisandra chinensis Baill

Schisandrin is the main active ingredient isolated from the fruit of Schisandra chinensis Baill. Recent studies have demonstrated that schisandrin exhibits anti-oxidative effects in vivo. In the present study, the effect of schisandrin on plasma nitrite concentration in lipopolysaccharide (LPS)-treated mice was evaluated. It also significantly inhibited carrageenan-induced paw edema and acetic acid-induced vascular permeability in mice. Furthermore, schisandrin had a protective effect on lipopolysaccharide (LPS)-induced sepsis. In vitro, our results are the first that show that the anti-inflammatory properties of schisandrin result from the inhibition of nitric oxide (NO) production, prostaglandin E 2 (PGE 2) release, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, which in turn results from the inhibition of nuclear factor-kappaB (NF-κB), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) activities in a RAW 264.7 macrophage cell line.

High throughput screening and antioxidant assay of dibenzo[a,c]cyclooctadiene lignans in modified‐ultrasonic and supercritical fluid extracts of Schisandra chinensis Baill by liquid chromatography–mass spectrometry and a free radical‐scavenging method

Dibenzo[a,c]cyclooctadiene lignans of Schisandra chinensis Baill are well known because of their hepatoprotective activity, antioxidant activity, and anticancer effect. For the isolation of the dibenzo[a,c]cyclooctadiene lignans of Schisandra chinensis Baill two extraction methods were used: modified-ultrasonic extraction and supercritical fluid extraction. A specific and fast analytical method for structure identification is established for quality control because structure elucidation could be accomplished by means of liquid chromatography-mass spectrometry (LC-MS) technologies. The separation and identification of the compounds were completed by: (i) a water-acetonitrile gradient system using a C18 reversed-phase column; (ii) UV detection at 225 nm; (iii) MS/MS experiments with electrospray ionization interface (ESI) ion trap mass spectrometry in the positive mode. Normalized collision energy was used to obtain fragment ions of structural relevance in the LC-MS/MS. These results provided a reliable LC-MS/MS method for the determination of the dibenzo[a,c]cyclooctadiene lignans from Schisandra chinensis Baill. Finally, we also detected 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging effects (%) of the modified-ultrasonic and supercritical fluid extracts of Schisandra chinensis Baill compared with 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox). The antioxidant activities of the modified-ultrasonic and supercritical fluid extracts were lower than that of trolox.

Traditional Chinese Medicines Wu Wei Zi (Schisandra chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch) Activate Pregnane X Receptor and Increase Warfarin Clearance in Rats

The traditional Chinese medicines (TCMs) are essential components of alternative medicines. Many TCMs are known to alter the expression of hepatic drug-metabolizing enzymes and transporters. The molecular mechanism by which TCMs and/or their constituents regulate enzyme and transporter expression, however, has remained largely unknown. In this report, we show that two TCMs, Wu Wei Zi (Schisandra chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch), and their selected constituents activate the xenobiotic orphan nuclear receptor pregnane X receptor (PXR). Treatment with TCM extracts and the Schisandrol and Schisandrin constituents of Wu Wei Zi induced the expression of drug-metabolizing enzymes and transporters in reporter gene assays and in primary hepatocyte cultures. The affected enzymes and transporters include CYP3A and 2C isozymes and the multidrug resistance-associated protein 2. In transient transfection and reporter gene assays, the Schisandrin constituents of Wu Wei Zi had an estimated EC50 of 2 and 1.25 microM on hPXR and mPXR, respectively. Interestingly, mutations that were intended to alter the pore of the ligand-binding cavity of PXR had species-specific effects on the activities of the individual Schisandrols and Schisandrins. In rats, the administration of Wu Wei Zi and Gan Cao increased the metabolism of the coadministered warfarin, reinforcing concerns involving the safe use of herbal medicines and other nutraceuticals to avoid PXR-mediated drug-drug interactions. Meanwhile, the activation of PXR and induction of detoxifying enzymes provide a molecular mechanism for the hepatoprotective effects of certain TCMs.

Preparative Separation and Purification of Schisandrin and Schisantherin from Schisandra Chinensis (Turcz) Baill by High Speed Countercurrent Chromatography

High speed countercurrent chromatography (HSCCC) was successfully applied to the preparative separation and purification of schisandrin and schisantherin from Schisandra chinensis (Turcz) Baill by microwave‐assisted extraction. The petroleum ether extract was separated with a two‐phase solvent system composed of n‐hexane‐ethyl acetate‐methanol‐water (22:8:20:20, v/v). The analysis of HPLC for each fraction from preparative HSCCC showed that the purity of schisandrin (16 mg) was over 98% and schisantherin (6 mg) was over 96% from the 100 mg of petroleum ether extract in a one‐step separation.

Separation and determination of active components inSchisandra chinensis Baill. and its medicinal preparations by non-aqueous capillary electrophoresis

A simple, economical and effective non-aqueous capillary electrophoresis separation and detection method was developed for the quantification of deoxyschizandrin and gamma-schizandrin in Schisandra chinensis Baill. and its medicinal preparations for the first time. After optimization of separation conditions, a buffer of 140 mmol/L sodium cholate in methanol was selected for separating the two analytes, but baseline separation of SA and SB in real samples was not obtained. Therefore second-order derivative electropherograms were applied for resolving overlapping peaks. Regression equations revealed good linear relationships (correlation coefficients 0.9975--0.9988) between peak heights in second-order derivative electropherograms and concentrations of the two analytes. The relative standard deviations (RSD) of the migration times and the peak height of the two constituents were in the ranges 0.62--0.79% and 0.25--2.17% (intra-day) and 1.43--2.06 and 4.08--5.72% (inter-day), respectively. The recoveries of the two constituents ranged from 93.2 to 103.0%. The results indicated that baseline separation of the analytes was sometimes hard to obtain in real samples and second-order derivative electropherograms were applicable for the resolution and analysis of overlapping peaks.

Kadsuranin: a lignan from the fruit ofSchisandra chinensis

The title compound, kadsuranin or 5,6,7,8-tetra­hydro-1,2,3,13-tetra­methoxy-6,7-di­methyl­benzo­[3,4]­cyclo­octa­[1,2-f][1,3]benzodioxole, C23H28O6, is a dibenzo­cyclo­octa­diene-type lignan which was isolated from a Chinese medicine, Schisandra chinensis (the fruit of Schisandra chinensis Baill.). The mol­ecule contains two six-membered aromatic rings, one five-membered ring, and an eight-membered ring with a twisted-boat–chair conformation.