Schisandrol A, the main active ingredient of Schisandrae Chinensis Fructus, inhibits pulmonary fibrosis through suppression of the TGF-ß signaling pathway as revealed by UPLC-Q-TOF/MS, network pharmacology and experimental verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis decoction derived from the book of Waitai Miyao (Tao Wang, Tang dynasty) is often used in the treatment of idiopathic pulmonary fibrosis (IPF), which is included in the Grand Ceremony of Chinese formulae (Huairen Peng, 1994). Schisandrae Chinensis Fructus (Sch) is one of the most important herbs in this formula. According to the "Shennong's Herbal Classicherbal" of the Han Dynasty, Sch has sour taste, warm nature, which has the effect of tonifying qi and curing cough. In addition, according to the "Compendium of Materia Medica" of the Ming Dynasty, Sch is used to treat cough and asthma, which has the effect of moistening the lung and tonifying the kidney. However, the active ingredients of Sch absorption into the plasma and its pharmacological mechanism of treatment for IPF still remained unclear. AIM OF THE STUDY: Our research aimed at identifying the absorbed active ingredients and metabolized of Sch in rat plasma and the mechanism of anti-IPF based on serum pharmacochemistry. MATERIALS AND METHODS: First, the rats were divided into control group and Sch group. Sch sample was orally administrated to the rats for seven days. The blood samples were drawn into an Eppendorf tube after the last dosing. The ultrahigh performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (UPLC-Q-TOF/MS) was applied to identify the absorption components and metabolites of Sch in rat plasma. Second, the network pharmacology combined with molecular docking analysis was further investigated to illuminate its potential mechanism of treatment for IPF by the biological targets regulating related pathways. Finally, the mechanism of action was verified by experimental in vitro and in vivo. RESULTS: A total of 78 compounds, consist of 13 prototype lignans and 65 metabolites (including isomers) were identified. Network pharmacology study and molecular docking analysis indicated that schisandrol A (L1) play an anti-fibrosis role by regulating the TGF-ß signaling pathway. Experimental in vitro and in vivo verified that the schisandrol A could inhibiting pulmonary fibrosis through TGF-ß signaling pathway. The effect and mechanism of schisandrol A inhibiting pulmonary fibrosis were reported for the first time. CONCLUSIONS: In this study, the absorption active ingredients of Sch in rat plasma were combined with the network pharmacology investigation and experimental in vitro and in vivo to elucidate its biological mechanism of treatment for IPF. The results provided a theoretical support for understanding the bioactive compounds and the pharmacological mechanism of Sch.

Hepatoprotective Constituents of Total Dibenzocyclooctadiene Lignans from Schisandra chinensis Based on the Spectrum-Effect Relationship.

To scientifically clarify the hepatoprotective constituents of Fructus Schizandrae chinensis, eleven batches samples of total dibenzocyclooctadiene lignans (TDL) from Schisandra chinensis were prepared by using the optimum extraction technique. Characteristic high-performance liquid chromatography (HPLC) chromatograms were obtained through HPLC analysis technology, and the hepatoprotective effects of the eleven batches of TDL were evaluated by MTT assay. Based on the chemical and biological activity results, the spectrum-effect relationship between the characteristic HPLC fingerprints and the hepatoprotective effect of TDL was established using Minitab 16.0 data analysis software. On the basis of the spectrum-effect relationship, thirteen compounds (1-13) were obtained from the TDL by chemical natural product chemical separation and purification technology, and their structures were identified on the basis of the spectral data and the literature. Based on these compounds, thirteen common peaks among the thirty-three chromatographic peaks in the above HPLC fingerprints were identified. Our findings showed that some components, including, schisandrin B (2), schisandrin A (3), and schisandrol B (7) had significant roles in promoting hepatoprotective activity. Preliminary verification of the spectrum-effect relationship of TDL from S. chinensis was carried out, and the results confirmed that the activity of a composite of these three key components in optimal ratios was better than that of any individual compound, which potentially confirmed the reliability of the spectrum-effect relationship and the synergistic effects of traditional Chinese medicine.

Schizandrin A ameliorates cognitive functions via modulating microglial polarisation in Alzheimer's disease mice.

CONTEXT: Schizandrin A (Sch A) is a major phytochemical from Schisandra chinensis (Turcz.) Baill. (Schisandraceae), which exerts a neuroprotective effect in Alzheimer's disease (AD). OBJECTIVE: To investigate the mechanism of Sch A in AD. MATERIALS AND METHODS: AD group: APP/PS1 transgenic mice served as AD models; AD + SCH group: APP/PS1 received 2 mg/kg Sch A by intragastric administration; WT: C57BL/6 mice were used as control. For in vitro assay, mouse microglial BV2 cells were treated with 0.5 µg/mL lipopolysaccharide or combined with 10 µmol/L Sch A for 24 h. The cognitive function and apoptosis in the mice was estimated. Microglial polarisation in the mice and cells was analysed. RESULTS: Sch A treatment effectively improved spatial learning and memory ability and suppressed apoptosis in the brain tissues of APP/PS1 mice. APP/PS1 mice exhibited an increase in the levels of Aß1-42 (2367.9 ± 431.1 pg/mg) and Aß1-40 (1753.3 ± 253.4 pg/mg), which was abolished by Sch A treatment. Moreover, Sch A treatment repressed the proportions of iNOS+/Iba-1+ cells and IL-6 expression, while enhanced the proportions of Arg-1+/Iba-1+ cells and IL-10 expression in APP/PS1 mice. In vitro, Sch A treatment reduced the proportions of CD16/32+ cells, iNOS expression and IL-6 levels (25.7 ± 5.3 pg/mL) repressed M1 polarisation, and enhanced the proportions of CD206 cells, Arg-1 expression and IL-10 levels (75.9 ± 12.8 pg/mL) in BV2 cells. CONCLUSIONS: This research confirms the neuroprotective effect of Sch A in AD, suggesting that Sch A may become a potential anti-AD agent.

Biomineralized separation, concentration, and evaluation of the effectiveness of Schisandra chinensis fruit extract.

Here, we detail the biomineralization-assisted separation and concentration of crude food extract and an evaluation of its effectiveness. Schisandra chinensis fruit extract was used as a model plant extract. Hybrid grape-like mineral was assembled by calcium carbonate mineralization. The hybrid particles of S. chinensis mineral were fully characterized using field emission scanning electron microscopy, X-ray diffraction, thermogravimetric analysis, and particle size analysis. Data including the Brunauer-Emmett-Teller surface area, single point total pore volume, and adsorption/desorption analysis of pore size were also investigated. Organic molecules, including lipids such as palmitic acid, stearic acid, and linolenic acid in the Schisandra chinensis fruit, affect the formation of complex structures involving the CaCO3 mineralization pathway by inhibiting crystallization. However, the cosmetic active primary components were entrapped in a similar proportion in the preserved extract, and were efficiently separated without additional filtering and concentration steps for purification. In addition, the hybrid mineral was enriched (10.5 times) in Gomisin N, a representative component of S. chinensis fruit, relative to its concentration in the initial extract samples. The hybrid mineral inhibited both intracellular and extracellular melanin production and increased the 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity. The data provide the first evidence of the potential use of fruit extract for obtaining hybrid minerals and the effectiveness of the biomineralization-based separation and concentration strategy.

Mechanisms dissection of the combination GRS derived from ShengMai preparations for the treatment of myocardial ischemia/reperfusion injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Recently, a new drug combination GRS comprising ginsenoside Rb1 (G-Rb1), ruscogenin (R-Rus) and schisandrin (S-SA) was screened based on ShengMai preparations, which exhibited a prominent cardioprotective effects against myocardial ischemia/reperfusion (MI/R) injury. AIM OF THE STUDY: To investigate their systemic and individual mechanism of each compound in combination GRS. MATERIALS AND METHODS: The mice model of MI/R and hypoxia/reoxygenation (H/R)-induced cardiomyocytes injury were performed to explore the respective characteristics of each compound in GRS against myocardial injury. RESULTS: Each component in the combination GRS attenuated MI/R injury as evidenced by decreased myocardial infarct size, ameliorated histological features, and improved biochemical indicators. Meanwhile, ingredient G, R and S in combination also individually performed a significant decrease of apoptotic index in MI/R mice and H/R-induced cardiomyocytes injury. Mechanistically, component G in GRS could markedly increase the ATP content in cardiomyocytes through activation of AMPKα phosphorylation. Interestingly, the anti-apoptotic actions of G were profoundly attenuated by knockdown of AMPKα, while no alteration was observed on composition R and S. Moreover, component R in GRS significantly reduced the IL-6 and TNF-α mRNA expression, as well as the content of IL-6 via the modulation of NF-κB signaling pathway. Further, component S exhibited the most powerful anti-oxidative capacity in GRS and remarkably decreased the production of MDA and ROS, and potential mechanisms might at least in part through activating the Akt-14-3-3 signaling pathway and inhibiting the phosphorylation of Bad and ERK1/2. CONCLUSIONS: Our results indicated that the respective mechanism of each compound in combination GRS against MI/R injury might closely associated with energy metabolism modulation, suppression of inflammation and oxidative stress.

CYP2C19 is involved in the effect of Wuzhi tablet (Schisandra sphenanthera extract) and its constituents on the pharmacokinetics of intravenous voriconazole.

The co-administration of voriconazole (VCZ) and Wuzhi tablet (WZ) is frequently prescribed for solid organ transplantation patients in China. However, the pharmacokinetic interactions between VCZ and WZ as well as its bioactive constituents, such as schisandrin A and schisandrol B, remain unknown. Therefore, the effects of WZ and the two lignans on the metabolism of VCZ and the potential role of cytochromeP450 (CYP450), especially cytochrome P450 2C19 (CYP2C19), were investigated. The results showed that WZ extensively inhibited the activities of CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4. Noteworthy, 2.5 mg/mL WZ almost completely inhibited the activity of 2C19, and the inhibition ratio reached 78.6±3% and 63.5±4.6% for schisandrin A and schisandrol B at concentrations 100 µM, respectively. In addition, rats were treated with a single or consecutive 14 day oral dose of WZ (250 mg/kg), schisandrol B (10 mg/kg) and schisandrin A (10 mg/ kg). In rats treated with WZ, the AUC0-∞ value for intravenous VCZ dosing was increased by 80.2% (single dose, p < 0.05) and 66.4% (dosage for 14 day, p < 0.05) and the Cmax was increased by 10.5% (p < 0.05) and (20.6%, p < 0.05), respectively, much greater than that when VCZ (28 mg/kg) was given alone. Unexpectedly, the AUC and Cmax values after schisandrol B and schisandrin A treatment were significantly increased. However, the mRNA expression of liver CYP2C19 and the protein expression of liver CYP2C19 were surprisingly increased after treatment with WZ, schisandrol B and schisandrin A in rats. Therefore, attention should be paid to when WZ and VCZ are administered concomitantly, as dosage adjustment might become necessary. Further clinical study is warranted to validate the interaction between WZ and VCZ.

Preventive Effects of Schisandrin A, A Bioactive Component of Schisandra chinensis, on Dexamethasone-Induced Muscle Atrophy.

Muscle wasting is caused by various factors, such as aging, cancer, diabetes, and chronic kidney disease, and significantly decreases the quality of life. However, therapeutic interventions for muscle atrophy have not yet been well-developed. In this study, we investigated the effects of schisandrin A (SNA), a component extracted from the fruits of Schisandra chinensis, on dexamethasone (DEX)-induced muscle atrophy in mice and studied the underlying mechanisms. DEX+SNA-treated mice had significantly increased grip strength, muscle weight, and muscle fiber size compared with DEX+vehicle-treated mice. In addition, SNA treatment significantly reduced the expression of muscle degradation factors such as myostatin, MAFbx (atrogin1), and muscle RING-finger protein-1 (MuRF1) and enhanced the expression of myosin heavy chain (MyHC) compared to the vehicle. In vitro studies using differentiated C2C12 myotubes also showed that SNA treatment decreased the expression of muscle degradation factors induced by dexamethasone and increased protein synthesis and expression of MyHCs by regulation of Akt/FoxO and Akt/70S6K pathways, respectively. These results suggest that SNA reduces protein degradation and increases protein synthesis in the muscle, contributing to the amelioration of dexamethasone-induced muscle atrophy and may be a potential candidate for the prevention and treatment of muscle atrophy.

Study on the potential effective ingredients of Xiaosheng prescription for dry eye disease.

Xiaosheng prescription (XSP) has been used for dry eye disease (DED) for more than 10 years in Eye Hospital of China Academy of Chinese Medicine Sciences. However, the effective ingredients involved have remained unclear, which was investigated in this study by the correlation of ingredient and therapeutic activity. Human corneal epithelial cells (HCEC) cultured with 110 mM NaCl solution in vitro and C57BL/6 mice injected subcutaneously with scopolamine hydrobromide were used to establish dry eye models, and the therapeutic effect of XSP extract 1 was better than that of XSP extract 2 significantly. Then, UPLC-Q-TOF/MS and data analysis program Progenesis QI and Makerlynx XS were used to analyze the potential effective ingredients of XSP, and 4 compounds were speculated and identified, in which Schisandrin and 1 µM of Schisantherin A could obviously increase the cell survival rate of injured cells on the cell model. It can be indicated that Schisandrin and Schisantherin A are probably the potential effective ingredients in XSP for DED.

Decoding biomass recalcitrance: Dispersion of ionic liquid in aqueous solution and efficient extraction of lignans with microwave magnetic field.

Alkaline ionic liquid aqueous solutions were used to extract biphenyl cyclooctene lignans derivatives, and hydrolyze to the free-state biphenyl cyclooctene lignans simultaneously from Schisandra chinensis by microwave-assisted heating. The hydrogen bonds formatted between ionic liquid and water molecular attacks the amorphous region of cellulose. Selective heating by microwave produce the more polar regions, which results in swelling and fragmentation of raw materials near the hot spots. Therefore, ionic liquid-microwave-assisted extraction method of free-state biphenyl cyclooctene lignans was set up. The solid residue after treatment was characterized by infrared spectroscopy and scanning electron microscopy, which showed that cellulose, hemicellulose, and lignin were removed partially. The water content of ionic liquid solution affected its viscosity and diffusivity, and in turns the extraction efficiency of lignans. The IL solutions with different mole fractions of IL were detected by FTIR and Raman spectroscopy, the result shows that IL solutions with higher water contents (>0.6) won't form clusters. The optimum hydrolysis conditions were 0.2 g of ionic liquid catalyst per 5.0 g of S. chinensis fruits, a microwave irradiation power of 600 W, and heating time of 12 min, which gave a yield of free-state biphenyl cyclooctene lignans of 4.12±0.37 mg g-1. Besides, a hydrolysis mechanism of ester-bond biphenyl cyclooctene lignans and decreasing "biomass recalcitrance effect" by ionic liquid microwave-assisted method was proposed.

Chemical constituents isolated from stems of Schisandra chinensis and their antifeedant activity against Tribolium castaneum.

One new sesquiterpene (α-iso-cubebenol acetate, 8), together with 9 known compounds (1-7, 9, 10) were isolated from the stems of Schisandra chinensis (Turcz.) Baill. by repeated silica gel column chromatography. Based on the results of MS, NMR spectra and comparing with literature data, the six dibenzocyclooctadiene lignans were identified as schizandrin A to C (1-3), schizandrin (4), schisantherin A (5) and gomisin J (6), the two sesquiterpenes were identified as α-iso-cubebenol (7) and α-iso-cubebenol acetate (8), while the two triterpenic acids were identified as ganwuweizic acid (9) and kadsuric acid (10). The antifeedant activity of the 10 compounds against Tribolium castaneum adults was tested. Gomisin J (6) exhibited activity at 1500 ppm concentration with 40.3% antifeeding index percentages. As for the dibenzocyclooctene lignans (compounds 1-3, 6), the number of methylenedioxies and the position of hydroxyl groups were the main factors to affect their antifeedant activities.

Schizandrin B Mitigates Rifampicin-Induced Liver Injury by Inhibiting Endoplasmic Reticulum Stress.

Schisandra chinensis is widely used and effective in protecting liver. There are many mechanisms of drug-induced hepatocyte injury, among which endoplasmic reticulum (ER) stress-induced cell injury plays an important role. However, little is known about whether schisandra chinensis can inhibit rifampicin (RFP)-induced hepatocyte injury by affecting ER stress. In our study, firstly, L02 cells were treated with different concentrations of RFP for different time intervals, and the apoptosis, survival rate and endoplasmic reticulum stress gene and protein expressions of glucose-regulated protein 78 (GRP 78), PKR-like ER kinase (PERK), activating transcription factor (ATF)4, C/EBP-homologus protein (CHOP), ATF6, arginine-rich, mutated in early stage tumors (ARMET), p-inositol-requiring enzyme 1 (IRE1) and X-box binding protein 1 (XBP-1) were measured. We found that RFP increased apoptosis of L02 cells, decreased cell survival, and increased the gene and protein expression levels of GRP78, PERK, ATF4, CHOP, ATF6, ARMET, p-IRE1 and XBP-1, suggesting that RFP could induce hepatocyte injury, and the degree of injury was positively correlated with the dose and time of RFP. Next, we treated RFP-damaged hepatocytes with schizandrin B. We found that schizandrin B increased cell survival rate in dose-dependent and time-dependent manner, decreased cell apoptosis rate, and reduced protein and gene expression levels of GRP78, PERK, ATF4, CHOP, ATF6, ARMET and XBP-1. These results indicate that schizandrin B alleviates RFP-induced injury in L02 cells by inhibiting ER stress.

Hepatoprotective Tetrahydrobenzocyclooctabenzofuranone Lignans from Kadsura longipedunculata.

Three new tetrahydrobenzocyclooctabenzofuranone lignan glucosides, longipedunculatins A-C (1-3), a new dibenzocyclooctadiene lignan glucoside, longipedunculatin D (4), a new dibenzocyclooctadiene lignan (5), five new tetrahydrobenzocyclooctabenzofuranone lignans (6-10), and two new simple lignans (11, 12) were isolated from the roots of Kadsura longipedunculata. Their structures and absolute configurations were established using a combination of MS, NMR, and experimental and calculated electronic circular dichroism data. Compound 7 showed moderate hepatoprotective activity against N-acetyl-p-aminophenol-induced toxicity in HepG2 cells with a cell survival rate at 10 µM of 50.8%. Compounds 2, 7, and 12 showed significant in vitro inhibitory effects with an inhibition rate of 55.1%, 74.9%, and 89.8% on nitric oxide production assays at 10 µM.

Determination of Schisandrin A and Schisandrin B in Traditional Chinese Medicine Preparation Huganpian Tablet by RP-HPLC.

A reverse phase (RP)-HPLC method for separation and determination of Schisandrin A and Schisandrin B was presented, using a C18 Bondclone column, with methanol-water (v/v = 68 : 32) as mobile phase at a flow-rate of 1.00 mL·min-1, and UV detection at 220 nm. The tested parameters included mobile phase composition and UV detection wavelength. Good linearities were observed within concentration ranges of Schisandrin A 0.008-4.8 mg·L-1 (r = 0.9996), and Schisandrin B 0.005-3.1 mg·L-1 (r = 0.9994), respectively. The limit of detection (LOD) (S/N = 3) were 0.005 mg·L-1 Schisandrin A and 0.002 mg·L-1 Schisandrin B, respectively. The method was applied to determine the 2 compounds in a traditional Chinese medicine preparation for treatment of hepatic diseases, Huganpian tablet. To eliminate matrix effect, Oasis hydrophilic lipophilic balance (HLB) solid-phase extraction (SPE) was used to purify the ultra-sonicately extracted solution of the drug sample. Combined with the HLB SPE purification procedure, the HPLC method gave satisfactory results for quantitation of Schisandrin A and Schisandrin B in 3 types of Huganpian tablet samples, with spiking recoveries ca. 98% (relative standard deviation (R.S.D.) ≤ 3.5%) (n = 5).

Stereoisomers of Schisandrin B Are Potent ATP Competitive GSK-3ß Inhibitors with Neuroprotective Effects against Alzheimer's Disease: Stereochemistry and Biological Activity.

Glycogen synthase kinase-3ß (GSK-3ß) is a key enzyme in hyperphosphorylation of tau proteins and is a promising therapeutic target in Alzheimer's disease (AD). Here, we reported, for the first time, that the stereoisomers of Schisandrin B (Sch B), (+)-1, (-)-1, (+)-2, and (-)-2, were potent GSK-3ß inhibitors. They were demonstrated to selectively target GSK-3ß in an orthosteric binding mode, with IC50 values of 340, 290, 80, and 70 nM, respectively. Further study showed that these stereoisomers can significantly increase the expression of p-GSK-3ß (Ser9) and decrease the expressions of p-GSK-3ß (Tyr216) and p-GSK-3ß (Tyr279). Finally, these compounds can alleviate the cell injury induced by Aß, and the cognitive disorders in AD mice, especially (+)-2 and (-)-2. Collectively, the stereoisomers of Sch B, especially (+)-2 and (-)-2, were found to be potential selective ATP-competitive GSK-3ß inhibitors, which further affected their anti-AD effects. These promising findings explained the biological target of Sch B in AD, and bring a new understanding in the stereochemistry and bioactivities of Sch B.

Impact of dibenzocyclooctadiene lignans from Schisandra chinensis on the redox status and activation of human innate immune system cells.

Redox signaling has been established as an essential component of inflammatory responses, and redox active compounds are of interest as potential immunomodulatory agents. Dibenzocyclooctadiene lignans isolated from Schisandra chinensis, a medicinal plant with widespread use in oriental medicine, have been implicated to possess immunomodulatory properties but their effects on the human innate immune system cells have not been described. In this contribution, data are presented on the impact of schisandrin, schisandrin B and schisandrin C on human monocytic cell redox status, as well as their impact on dendritic cell maturation and T cell activation capacity and cytokine production. In THP-1 cells, levels of intracellular reactive oxygen species (ROS) were elevated after 1 h exposure to schisandrin. Schisandrin B and schisandrin C decreased cellular glutathione pools, which is a phenotype previously reported to promote anti-inflammatory functions. Treatment of human primary monocytes with the lignans during their maturation to dendritic cells did not have any effect on the appearance of surface markers HLA-DR and CD86 but schisandrin B and schisandrin C suppressed the secretion of cytokines interleukin (IL)-6, IL-10 and IL-12 by the mature dendritic cells. Dendritic cells maturated in presence of schisandrin C were further cocultured with naïve CD4+ T cells, resulting in reduced IL-12 production. In THP-1 cells, schisandrin B and schisandrin C reduced the IL-6 and IL-12 production triggered by E. coli lipopolysaccharide and IL-12 production induced by an infection with Chlamydia pneumoniae. In conclusion, the studied lignans act as immunomodulatory agents by altering the cytokine secretion, but do not interfere with dendritic cell maturation. And the observed effects may be associated with the ability of the lignans to alter cellular redox status.

Schisantherin A alleviated alcohol-induced liver injury by the regulation of alcohol metabolism and NF-kB pathway.

Schisantherin A (SinA), one of the most abundant active ingredients of Schisandra chinensis, was reported to protect and benefit the liver, however, its effect on alcohol-induced liver injury (ALI) was still not clear. In the present study, an ALI mice model was induced by feeding mice an alcohol-containing liquid diet for four weeks. Then, 100 mg/kg or 200 mg/kg SinA was administered to mice every day by gavage for the last two weeks. Histopathological analysis showed that alcohol-induced liver lipid vacuoles were reduced by SinA. The activities of aspartate aminotransferase (AST, 61.90 ± 14.65 vs. 93.65 ± 20.50, 50.46 ± 13.21 vs. 93.65 ± 20.50) and alanine transaminase (ALT, 41.29 ± 9.20 vs. 64.04 ± 18.13, 36.52 ± 7.71 vs. 64.04 ± 18.13) in the serum of ALI mice were significantly reduced by 100 mg/kg or 200 mg/kg SinA when compared with control mice. Alcohol-induced oxidative stress and the inflammatory response in the liver were suppressed by SinA in a dose-dependent manner. Meanwhile, treatment with SinA decreased alcohol dehydrogenase (ADH) activity and increased acetaldehyde dehydrogenase (ALDH) activity in ALI mice. Alcohol-induced upregulation of CYP2E1 and CYP1A2 in the liver was inhibited by SinA. Further, SinA suppressed activation of the NF-kB pathway in ALI mice. In conclusion, our findings demonstrate that SinA is able to protect against ALI, and this may be, at least in part, caused by regulation of alcohol metabolism and the NF-kB pathway. Our data suggest a therapeutic potential of SinA in the treatment of ALI.

Evaluation of neuroactive effects of ethanol extract of Schisandra chinensis, Schisandrin, and Schisandrin B and determination of underlying mechanisms by zebrafish behavioral profiling.

Schisandra chinensis, a traditional Chinese medicine (TCM), has been used to treat sleep disorders. Zebrafish sleep/wake behavioral profiling provides a high-throughput platform to screen chemicals, but has never been used to study extracts and components from TCM. In the present study, the ethanol extract of Schisandra chinensis and its two main lignin components, schisandrin and schisandrin B, were studied in zebrafish. We found that the ethanol extract had bidirectional improvement in rest and activity in zebrafish. Schisandrin and schisandrin B were both sedative and active components. We predicted that schisandrin was related to serotonin pathway and the enthanol extract of Schisandra chinensis was related to seoronin and domapine pathways using a database of zebrafish behaviors. These predictions were confirmed in experiments using Caenorhabditis elegans. In conclusion, zebrafish behavior profiling could be used as a high-throughput platform to screen neuroactive effects and predict molecular pathways of extracts and components from TCM.

An overview of neuroprotective and cognitive enhancement properties of lignans from Schisandra chinensis.

Schisandra chinensis fruits have been traditionally used for thousands of years in Korea, China and Japan to treat various ailments. The fruits contain a variety of bioactive metabolites, especially lignan components have been reported to have various biological activities and have potential in the treatment of numerous neurodegenerative diseases. The lignans from S. chinensis are mainly grouped under dibenzocyclooctadiene lignans. Previous studies have reported that the crude extracts and the isolated pure lignan components effectively protect the neuronal cell damage and significantly enhance the cognitive performances. The experimental findings support the extracts and lignan components from S. chinensis can be used as new therapeutic agents to treat various neurodegenerative diseases. In the current review, we highlight the lignans from S. chinensis as promising resources for the development of natural and effective agents for neuroprotective and cognitive enhancement effects. The lignan extracts and individual compounds from S. chinensis were summarized in relation to their neuroprotective and cognitive enhancement activities.

Anti-melanogenic effect of gomisin N from Schisandra chinensis (Turcz.) Baillon (Schisandraceae) in melanoma cells.

Overproduction and accumulation of melanin in the skin can lead to pigmentation disorders, such as freckles and melasma. Many researchers are studying the regulation of melanogenesis in the skin with the aim of developing whitening cosmetics. In this study, bioactivity-guided separation of the hexane fraction of Schisandra chinensis (Turcz.) Baillon extract yielded five major compounds, ß-chamigrenal, α-ylangenol, gomisin N, gomisin A, and schisandrin. The structures were identified by using 1H-NMR and 13C-NMR spectroscopy and comparing the spectral data with published data. Melanogenesis inhibitory activity assay in alpha-melanocyte-stimulating hormone (α-MSH)-induced B16F10 mouse melanoma cells revealed that gomisin N was the active component and significantly inhibited melanin synthesis in a concentration-dependent manner. Thus, we evaluated the mechanism underlying its anti-melanogenic effect. Gomisin N inhibited the expression of tyrosinase and microphthalmia-associated transcription factor (MITF) in B16F10 cells, while it did not affect cAMP response element binding protein (CREB) phosphorylation. Additionally, gomisin N activated AKT phosphorylation, which inhibits MITF expression. Thus, our results strongly suggest that the active compound, gomisin N, has potential for use in cosmetics to reduce hyperpigmentation.