RESUMO
A novel galacturonoglucan, named SCP-1, is isolated and purified from Schisandra chinensis fruits. The structure of SCP-1 is systematically investigated by a combination of monosaccharide compositions, absolute Mw, methylation analysis, partial acid hydrolysis, isoamylase degradations, and nuclear magnetic resonance spectroscopy. The structure of SCP-1 is theoretically described as follows: (i) Glc and GalA in a molar ratio of 17:3; (ii) â 4)-α-Glcp-(1â, â4,6)-α-Glcp-(1â, â3,4,6)-α-Glcp-(1â, α-Glcp-(1â, â4)-α-GalAp-6-OMe-(1â, α-GalAp-6-OMe-(1â, ß-Glcp-(1â, â6-)-ß-Glcp-(1 â and â3,4)-ß-Glcp-(1 â in a molar ratio of 48:5:3:3:10:5:12:5:9; (iii) a repeating unit of â4)-α-Glcp-(1 â as a backbone with branched points at C-3 and C-6, substituted by different types of acidic and neutral side chains to form multiple branches; and (iv) a rigid rod configuration deduced from α value of 1.26 in Mark-Houwink equation ([η] = kMα). Anti-tumor assay investigated the effects of SCP-1 on human HepG2 cancer cell lines in vitro. This is for the first time to report a galacturonoglucan in S. chinensis fruits.
Assuntos
Schisandra , Humanos , Schisandra/química , Frutas , Linhagem CelularRESUMO
This study aimed to isolate and identify antibacterial compounds from Schisandra chinensis (S. chinensis) that are effective against the Streptococcus mutans KCCM 40105 strain. First, S. chinensis was extracted using varying concentrations of ethanol, and the resulting antibacterial activity was evaluated. The 30% ethanol extract of S. chinensis showed high activity. The fractionation and antibacterial activity of a 30% ethanol extract from S. chinensis were examined using five different solvents. Upon investigation of the antibacterial activity of the solvent fraction, the water and butanol fractions showed high activity, and no significant difference was found. Therefore, the butanol fraction was chosen for material exploration using silica gel column chromatography. A total of 24 fractions were obtained from the butanol portion using silica gel chromatography. The fraction with the highest antibacterial activity was Fr 7. From Fr 7, thirty-three sub-fractions were isolated, and sub-fraction 17 showed the highest level of antibacterial activity. A total of five peaks were obtained through the pure separation of sub-fraction 17 using HPLC. Peak 2 was identified as a substance exhibiting a high level of antibacterial activity. Based on the results of UV spectrometry, 13C-NMR, 1H-NMR, LC-MS, and HPLC analyses, the compound corresponding to peak number 2 was identified as tartaric acid.
Assuntos
Schisandra , Streptococcus mutans , Schisandra/química , Solventes/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Cromatografia Líquida , Etanol/química , Cromatografia Líquida de Alta Pressão , Antibacterianos/química , ButanóisRESUMO
Purpose: To study the active components, drug targets and mechanism of Schisandra chinensis (S.chinensis) combined with coenzyme Q10 (CQ10) in the treatment of heart failure (HF). Methods: Network pharmacology combined with the gene expression omnibus chip method to analyze the main pathways by which S.chinensis combined with CQ10 functioned to treat heart failure. Subsequently, the biological activities of the major pathway key proteins and their corresponding compounds were verified by molecular docking techniques. Finally, the molecular mechanism of S. chinensis combined with CQ10 for the treatment of heart failure was verified using a rat heart failure model induced by isoproterenol hydrochloride and using hematoxylin-eosin staining, TUNEL, immunohistochemistry and Western blot. Results: Network pharmacology combined with experimental validation suggests that the mechanism of action of S.chinensis combined with CQ10 in the treatment of heart failure may involve CQ10, Citral, Schisandrone, Schisanhenol B, Gomisin O, Schisandrin C and other components, which may synergistically inhibit the PI3K-AKT signaling pathway and affect the expression of AKT1, PIK3CG and other targets on this pathway. In addition, S. chinensis combined with CQ10 could effectively improve the cardiac coefficients of rats with heart failure, reduce the area of myocardial fibrosis and lowered the serum levels of IL-1ß and TNF-α in heart failure rats, as well as reduced cardiac myocyte apoptosis, increased Bcl-2 expression and decreased p-PI3K/PI3K, p-AKT/AKT, P65 and Bax expression in cardiac tissue. Comparison of the results showed that the combination of S.chinensis and CQ10 was more effective compared with CQ10 alone, ie, the ability of S.chinensis combined with CQ10 in improving cardiac function, inhibiting cardiomyocyte apoptosis and reducing inflammatory response lies in the synergistic effect of PI3K/AKT signaling pathway. Conclusion: The therapeutic effect of S.chinensis combined with CQ10 on heart failure, which may occur through the inhibition of PI3K/AKT signaling pathway.
Assuntos
Medicamentos de Ervas Chinesas , Insuficiência Cardíaca , Schisandra , Ratos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Schisandra/química , Fosfatidilinositol 3-Quinases/metabolismo , Ratos Sprague-Dawley , Simulação de Acoplamento Molecular , Insuficiência Cardíaca/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Hepatocellular carcinoma (HCC) poses a growing challenge to global health efforts. The 5-year survival rate of HCC patients is still dismal. A traditional prescription Qi-Wei-Wan (QWW) comprising Astragali Radix and Schisandra chinensis Fructus has traditionally been used for HCC treatment according to traditional Chinese medicine theory, but the pharmacological basis is not clear. AIM OF THE STUDY: This study aims to investigate the anti-HCC effects of an ethanolic extract of QWW (hereafter, QWWE) and the mechanism of action. MATERIALS AND METHODS: An UPLC-Q-TOF-MS/MS method was developed to control the quality of QWWE. Two human HCC cell lines (HCCLM3 and HepG2) and a HCCLM3 xenograft mouse model were employed to investigate the anti-HCC effects of QWWE. The anti-proliferative effect of QWWE in vitro was determined by MTT, colony formation and EdU staining assays. Apoptosis and protein levels were examined by flow cytometry and Western blotting, respectively. Nuclear presence of signal transducer and activator of transcription 3 (STAT3) was examined by immunostaining. Transient transfection of pEGFP-LC3 and STAT3C plasmids was performed to assess autophagy and determine the involvement of STAT3 signaling in QWWE's anti-HCC effects, respectively. RESULTS: We found that QWWE inhibited the proliferation of and triggered apoptosis in HCC cells. Mechanistically, QWWE inhibited the activation of SRC and STAT3 at Tyr416 and Tyr705, respectively; inhibited the nuclear translocation of STAT3; lowered Bcl-2 protein levels, while increased Bax protein levels in HCC cells. Over-activating STAT3 attenuated the cytotoxic and apoptotic effects of QWWE in HCC cells. Moreover, QWWE induced autophagy in HCC cells by inhibiting mTOR signaling. Blocking autophagy with autophagy inhibitors (3-methyladenine and chloroquine) enhanced the cytotoxicity, apoptotic effect and the inhibitory effect on STAT3 activation of QWWE. Intragastric administration of QWWE at 10 mg/kg and 20 mg/kg potently repressed tumor growth and inhibited STAT3 and mTOR signaling in tumor tissues, but did not significantly affect mouse body weight. CONCLUSION: QWWE exhibited potent anti-HCC effects. Inhibiting the STAT3 signaling pathway is involved in QWWE-mediated apoptosis, while blocking mTOR signaling contributes to QWWE-mediated autophagy induction. Blockade of autophagy enhanced the anti-HCC effects of QWWE, indicating that the combination of an autophagy inhibitor and QWWE might be a promising therapeutic strategy for HCC management. Our findings provide pharmacological justifications for the traditional use of QWW in treating HCC.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Schisandra , Humanos , Animais , Camundongos , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Linhagem Celular Tumoral , Espectrometria de Massas em Tandem , Apoptose , Serina-Treonina Quinases TOR/metabolismo , Autofagia , Proliferação de CélulasRESUMO
Huntington's disease (HD) is a neurodegenerative disease that affects the motor control system of the brain. Its pathological mechanism and therapeutic strategies have not been fully elucidated yet. The neuroprotective value of micrandilactone C (MC), a new schiartane nortriterpenoid isolated from the roots of Schisandra chinensis, is not well-known either. Here, the neuroprotective effects of MC were demonstrated in 3-nitropropionic acid (3-NPA)-treated animal and cell culture models of HD. MC mitigated neurological scores and lethality following 3-NPA treatment, which is associated with decreases in the formation of a lesion area, neuronal death/apoptosis, microglial migration/activation, and mRNA or protein expression of inflammatory mediators in the striatum. MC also inhibited the activation of the signal transducer and activator of transcription 3 (STAT3) in the striatum and microglia after 3-NPA treatment. As expected, decreases in inflammation and STAT3-activation were reproduced in a conditioned medium of lipopolysaccharide-stimulated BV2 cells pretreated with MC. The conditioned medium blocked the reduction in NeuN expression and the enhancement of mutant huntingtin expression in STHdhQ111/Q111 cells. Taken together, MC might alleviate behavioral dysfunction, striatal degeneration, and immune response by inhibiting microglial STAT3 signaling in animal and cell culture models for HD. Thus, MC may be a potential therapeutic strategy for HD.
Assuntos
Doença de Huntington , Doenças Neurodegenerativas , Schisandra , Animais , Microglia/metabolismo , Doença de Huntington/metabolismo , Doenças Neurodegenerativas/metabolismo , Fator de Transcrição STAT3/metabolismo , Meios de Cultivo Condicionados/farmacologiaRESUMO
The pathogenicity of foodborne Vibrio parahaemolyticus is a major concern for global public health. This study aimed to optimize the liquid-solid extraction of Wu Wei Zi extracts (WWZE) against Vibrio parahaemolyticus, identify its main components, and investigate the anti-biofilm action. The extraction conditions optimized by the single-factor test and response surface methodology were ethanol concentration of 69%, temperature at 91 °C, time of 143 min, and liquid-solid ratio of 20:1 mL/g. After high performance liquid chromatography (HPLC) analysis, it was found that the main active ingredients of WWZE were schisandrol A, schisandrol B, schisantherin A, schisanhenol, and schisandrin A-C. The minimum inhibitory concentration (MIC) of WWZE, schisantherin A, and schisandrol B measured by broth microdilution assay was 1.25, 0.625, and 1.25 mg/mL, respectively, while the MIC of the other five compounds was higher than 2.5 mg/mL, indicating that schisantherin A and schizandrol B were the main antibacterial components of WWZE. Crystal violet, Coomassie brilliant blue, Congo red plate, spectrophotometry, and Cell Counting Kit-8 (CCK-8) assays were used to evaluate the effect of WWZE on the biofilm of V. parahaemolyticus. The results showed that WWZE could exert its dose-dependent potential to effectively inhibit the formation of V. parahaemolyticus biofilm and clear mature biofilm by significantly destroying the cell membrane integrity of V. parahaemolyticus, inhibiting the synthesis of intercellular polysaccharide adhesin (PIA), extracellular DNA secretion, and reducing the metabolic activity of biofilm. This study reported for the first time the favorable anti-biofilm effect of WWZE against V. parahaemolyticus, which provides a basis for deepening the application of WWZE in the preservation of aquatic products.
Assuntos
Schisandra , Vibrio parahaemolyticus , Vibrio parahaemolyticus/genética , BiofilmesRESUMO
The present study optimized the ethanol extraction process of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus drug pair by network pharmacology and Box-Behnken method. Network pharmacology and molecular docking were used to screen out and verify the potential active components of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus, and the process evaluation indexes were determined in light of the components of the content determination under Ziziphi Spinosae Semen and Schisandrae Sphenantherae Fructus in the Chinese Pharmacopoeia(2020 edition). The analytic hierarchy process(AHP) was used to determine the weight coefficient of each component, and the comprehensive score was calculated as the process evaluation index. The ethanol extraction process of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus was optimized by the Box-Behnken method. The core components of the Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus drug pair were screened out as spinosin, jujuboside A, jujuboside B, schisandrin, schisandrol, schisandrin A, and schisandrin B. The optimal extraction conditions obtained by using the Box-Behnken method were listed below: extraction time of 90 min, ethanol volume fraction of 85%, and two times of extraction. Through network pharmacology and molecular docking, the process evaluation indexes were determined, and the optimized process was stable, which could provide an experimental basis for the production of preparations containing Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus.
Assuntos
Farmacologia em Rede , Extratos Vegetais , Tecnologia Farmacêutica , Etanol , Simulação de Acoplamento Molecular , Sementes/química , Ziziphus/química , Extratos Vegetais/química , Schisandra/química , Frutas/químicaRESUMO
The kidney-shaped, red-colord fruit from the plant, Schisandra chinensis (Turcz.) Baill, which belongs to the Schisandraceae family, is among the most popular remedies used in traditional Chinese medicine. The English name of the plant is "Chinese magnolia vine". It has been used in Asia since ancient times to treat a variety of ailments, including chronic cough and dyspnea, frequent urination, diarrhea, and diabetes. This is because of the wide range of bioactive constituents, such as lignans, essential oils, triterpenoids, organic acids, polysaccharides, and sterols. In some cases, these constituents affects the pharmacological efficacy of the plant. Lignans with a dibenzocyclooctadiene-type skeleton are considered to be the major constituents and main bioactive ingredients of Schisandra chinensis. However, because of the complex composition of Schisandra chinensis, the extraction yields of lignans are low. Thus, it is particularly important to study pretreatment methods used during sample preparation for the quality control of traditional Chinese medicine. Matrix solid-phase dispersion extraction (MSPD) is a comprehensive process involving destruction, extraction, fractionation, and purification. The MSPD method is simple, it requires only a small number of samples and solvents, it does not require any special experimental equipments or instruments, and it can be used to prepare liquid, viscous, semi-solid, solid samples. In this study, a method combining matrix solid-phase dispersion extraction with high performance liquid chromatography (MSPD-HPLC) was established for the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis. The target compounds were separated on a C18 column with a gradient elution of 0.1% (v/v) formic acid aqueous solution and acetonitrile as the mobile phases, and detection was performed at a wavelength of 250 nm. First, the effects of 12 adsorbents, including silica gel, acidic alumina, neutral alumina, alkaline alumina, Florisil, Diol, XAmide, Xion, and the inverse adsorbents, C18, C18-ME, C18-G1, and C18-HC, on the extraction yields of lignans were investigated. Second, effects of the mass of the adsorbent, the type of eluent, and volume of eluent on the extraction yields of lignans were investigated. Xion was chosen as an adsorbent for MSPD-HPLC analysis of lignans from Schisandra chinensis. Optimization of the extraction parameters showed that the MSPD method had a high lignan extraction yield with Schisandra chinensis powder (0.25 g) as a fixed value, Xion as the adsorbent (0.75 g), and methanol as the elution solvent (15 mL). Analytical methods were developed for five lignans from Schisandra chinensis and these methods showed good linearity (correlation coefficients (R2)≥ 0.9999) for each target analyte. The limits of detection and quantification ranged from 0.0089 to 0.0294 µg/mL and 0.0267 to 0.0882 µg/mL, respectively. Lignans were tested at low, medium, and high levels. The average recovery rates were 92.2% to 111.2%, and the relative standard deviations were 0.23% to 3.54%. Both intra-day and inter-day precisions were less than 3.6%. Compared with hot reflux extraction and ultrasonic extraction methods, MSPD has the advantages of combined extraction and purification, being less time-consuming, and requiring lower solvent volumes. Finally, the optimized method was successfully applied to analyze five lignans from Schisandra chinensis samples from 17 cultivation areas.
Assuntos
Lignanas , Schisandra , Cromatografia Líquida de Alta Pressão , Solventes , Óxido de AlumínioRESUMO
In the present study, a novel and green temperature-responsive deep eutectic solvent (TRDES) system was developed and applied for the simultaneous extraction and separation of different polar active phytochemicals from Schisandra chinensis (Turcz.) Baill. The TRDES, consisting of amino alcohols and phenolic compounds, was chosen as the switching medium, and an upper critical solution temperature (UCST) type switchable solvent was obtained by adding an inorganic salt solution. The switchable phase diagram was plotted based on the relationship between the phase change temperature, the concentration and the amount of sodium chloride solution. Under optimal parameters, the yields with TRDES for different polar active phytochemicals (lignanoids and polysaccharides) from the dried fruit of Schisandra chinensis (DFSC) were 1.62 â¼ 1.17-fold and 1.39-fold to those with conventional solvents. Also, the TRDES system was still effective on extraction of DFSC lignanoids and polysaccharides after four cycles of extraction. The separated polysaccharides and lignanoids both had strong antioxidant activities with IC50 values of 1.92 mg/ mL and 0.10 mg/ mL against 2,2'-Azinobis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS), respectively. The extraction mechanism of TRDES was postulated by Density functional theory (DFT) calculations the hydrogen bonding in TRDES was the main factor to the higher extraction yield. This temperature-responsive deep eutectic solvent could be widely used for the efficient extraction and separation of multi-polar components. As a green and recyclable solvents, TRDES has great potential for the lower cost production from plants.
Assuntos
Solventes Eutéticos Profundos , Schisandra , Temperatura , Compostos Fitoquímicos , Solventes , Extratos VegetaisRESUMO
In order to establish structural-fingerprinting of polysaccharides for improvement of quality assessment, a sample preparation method based on microwave assisted free radical degradation (MFRD) of plant polysaccharides was proposed to produce oligosaccharides and small Mw polysaccharides. As a case study of Schisandra chinensis and S. sphenanthera fruit polysaccharides (SCP and SSP), the MFRD condition (i.e., 100 °C, 30 s and 80 W) was confirmed to be optimal. The potential structures of the MFRD products of SCP and SSP were further discussed by combinations of HILIC-ESI--QTOF-MSE and HILIC-ESI--Q-OT-IT-MS/MS. As followed, multivariable statistical analysis shows a clear separation of SCP and the SSP in PCA and OPLS-DA plots based HILIC-ESI--QTOF-MSE data. The VIP plot unveils several key Q-markers (e.g., peaks 3, 8, 9, 10, 15, 25, 26, 28, 29 and 30) with significant differences and stable emergences. Furthermore, a low-polymerization compositional fingerprinting was successfully constructed for SCP and SSP using a high-performance anion-exchange chromatography with pulsed amperometric detection. Compared to the conventional sample preparation methods, the MFRD took only a few thousandth of the time to accomplish degradations of plant polysaccharides. It significantly improves sample preparations and is generally applicable to various polysaccharide samples.
Assuntos
Schisandra , Schisandra/química , Espectrometria de Massas em Tandem , Micro-Ondas , Polissacarídeos/química , Radicais LivresRESUMO
Schisandra chinensis, a traditional Chinese medicinal herb, is rich in chemical constituents, including lignans, triterpenes, polysaccharides, and volatile oils. Clinically, it is commonly used to treat cardiovascular, cerebrovascular, liver, gastrointestinal, and respiratory diseases. Modern pharmacological studies have shown that S. chinensis extract and monomers have multiple pharmacological activities in lowering liver fat, alleviating insulin resistance, and resisting oxidative stress, and have good application prospects in alleviating nonalcoholic fatty liver disease(NAFLD). Therefore, this study reviewed the research progress on chemical constituents of S. chinensis and its effect on NAFLD in recent years to provide references for the research on S. chinensis in the treatment of NAFLD.
Assuntos
Resistência à Insulina , Lignanas , Hepatopatia Gordurosa não Alcoólica , SchisandraRESUMO
Background: Diabetic kidney disease (DKD) is a major cause of end-stage renal disease (ESRD), and inflammation is the main causative mechanism. Schisandra chinensis fruit Mixture (SM) is an herbal formulation that has been used for a long time to treat DKD. However, its pharmacological and molecular mechanisms have not been clearly elucidated. The aim of this study was to investigate the potential mechanisms of SM for the treatment of DKD through network pharmacology, molecular docking and experimental validation. Methods: The chemical components in SM were comprehensively identified and collected using liquid chromatography-tandem mass spectrometry (LC-MS) and database mining. The mechanisms were investigated using a network pharmacology, including obtaining SM-DKD intersection targets, completing protein-protein interactions (PPI) by Cytoscape to obtain key potential targets, and then revealing potential mechanisms of SM for DKD by GO and KEGG pathway enrichment analysis. The important pathways and phenotypes screened by the network analysis were validated experimentally in vivo. Finally, the core active ingredients were screened by molecular docking. Results: A total of 53 active ingredients of SM were retrieved by database and LC-MS, and 143 common targets of DKD and SM were identified; KEGG and PPI showed that SM most likely exerted anti-DKD effects by regulating the expression of AGEs/RAGE signaling pathway-related inflammatory factors. In addition, our experimental validation results showed that SM improved renal function and pathological changes in DKD rats, down-regulated AGEs/RAGE signaling pathway, and further down-regulated the expression of TNF-α, IL-1ß, IL-6, and up-regulated IL-10. Molecular docking confirmed the tight binding properties between (+)-aristolone, a core component of SM, and key targets. Conclusion: This study reveals that SM improves the inflammatory response of DKD through AGEs/RAGE signaling pathway, thus providing a novel idea for the clinical treatment of DKD.
Assuntos
Farmacologia em Rede , Schisandra , Animais , Ratos , Simulação de Acoplamento Molecular , Frutas , Transdução de Sinais , Produtos Finais de Glicação AvançadaRESUMO
Schisandra chinensis (S. chinensis) is an herbal medicine used for the treatment of Alzheimer's disease (AD). The purified polysaccharide fraction, namely SCP2, was previously isolated from S. chinensis crude polysaccharide (SCP) and its structure and in vitro activity were investigated. However, the in vivo activity of SCP2 and its potential mechanism for the treatment of AD have yet to be determined. This study used a combination of microbiomics and metabolomics to comprehensively explore the microbiota and metabolic changes in AD rats under SCP2 intervention, with the aim of elucidating the potential mechanisms of SCP2 in the treatment of AD. SCP2 showed significant therapeutic effects in AD rats, as evidenced by improved learning and memory capacity, reduced neuroinflammation, and restoration of the integrity of the intestinal barrier. Fecal metabolomic and microbiomic analyses revealed that SCP2 significantly modulated 19 endogenous metabolites and reversed gut microbiota disorders in AD rats. Moreover, SCP2 significantly increased the content of short-chain fatty acid (SCFAs) in the AD rats. Correlation analysis showed a significant correlation between gut microbes, metabolites and the content of SCFAs. Collectively, these findings will provide the basis for further development of SCP2.
Assuntos
Doença de Alzheimer , Microbioma Gastrointestinal , Schisandra , Ratos , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Schisandra/química , Metabolômica , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Polissacarídeos/química , Fezes/químicaRESUMO
Platelet-derived growth factor receptor ß (PDGFRß) plays an important role in hepatic fibrosis and is closely associated with hepatic stellate cells (HSCs) activation. Previously, by modeling PDGFRß affinity chromatography, we found that gomisin D can target PDGFRß. However, whether gomisin D has anti-fibrosis effects through targeting PDGFRß remained unclear. In this study, the effect of gomisin D on hepatic fibrosis was evaluated in vivo and vitro. HSC cell lines and primary HSC were cultured and functionally we found that gomisin D promotes HSC apoptosis, inhibits HSCs activation and proliferation. A male BALB/c mouse liver fibrosis model was established to comfirm gomisin D (especially in 50 mg/kg) could improve liver fibrosis by inhibiting HSCs activation. In addition, gomisin D had a good binding ability with PDGFRß (KD = 3.3e-5 M). Mechanically, gomisin D regulated PDGF-BB/PDGFRß signaling pathway by targeting PDGFRß, further more inhibited HSC activation, subsequently inhibited inflammatory factors, ultimately improved CCl4-induced liver fibrosis. Overall, gomisin D could inhibit HSC proliferation and activation, promote HSC apoptosis, and alleviate CCl4-induced hepatic fibrosis by targeting PDGFRß and regulating PDGF-BB/PDGFRß signaling pathway. This study provides a new drug for anti-liver firbosis therapy, and elucidates the deeper mechanism of gomisin D against HSCs activation by targeting PDGFRß.
Assuntos
Indóis , Lignanas , Fígado , Schisandra , Schisandra/química , Lignanas/farmacologia , Indóis/farmacologia , Masculino , Camundongos , Animais , Camundongos Endogâmicos BALB C , Células-Tronco Hematopoéticas/metabolismo , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Fibrose/metabolismo , Tetracloreto de Carbono , Transdução de Sinais , HumanosRESUMO
Due to green and environment-friendly characteristics, ultra-high-performance supercritical fluid chromatography has been widely used in analytical fields in recent years, but until now few reports are available for monosaccharide compositional analysis of macromolecule polysaccharides. In this study, an ultra-high-performance supercritical fluid chromatography technology with an unusual binary modifier is used to determine the monosaccharide compositions of natural polysaccharides. Each carbohydrate herein is simultaneously labeled as 1-pheny-3-methyl-5-pyrazolone and acetyl-derivative via pre-column derivatizations aiming to increase UV absorption sensitivity and decrease water solubility. Ten common monosaccharides are fully separated and detected on ultra-high-performance supercritical fluid chromatography combined with a photo-diode array detector by systematic optimization of multiple relevant parameters, for example, column stationary phases, organic modifiers, additives, flow rates, and so on. Compared with carbon dioxide as a mobile phase, the addition of a binary modifier increases the resolution of analytes. Additionally, this method has the advantages of small consumption of organic solvent, safety, and being environmental-friendly. It has been successfully applied for full monosaccharide compositional analysis of heteropolysaccharides from Schisandra chinensis fruits. To sum up, a new alternative approach is provided for monosaccharide compositional analysis of natural polysaccharides.
Assuntos
Cromatografia com Fluido Supercrítico , Schisandra , Monossacarídeos/análise , Cromatografia com Fluido Supercrítico/métodos , Frutas/química , PolissacarídeosRESUMO
Schisandra chinensis (S. chinensis) berries, originally a component of traditional herbal medicine in China, Korea, and other east Asian countries, are also valuable agents in modern phototherapy. S. chinensis berry preparations, including extracts and their chemical components, demonstrate anti-cancer, hepatoprotective, anti-inflammatory, and antioxidant properties, among others. These valuable properties, and their therapeutic potential, are conditioned by the unique chemical composition of S. chinensis berries, particularly their lignan content. About 40 of these compounds, mainly dibenzocyclooctane type, were isolated from S. chinensis. The most important bioactive lignans are schisandrin (also denoted as schizandrin or schisandrol A), schisandrin B, schisantherin A, schisantherin B, schisanhenol, deoxyschisandrin, and gomisin A. The present work reviews newly-available literature concerning the cardioprotective potential of S. chinensis berries and their individual components. It places special emphasis on the cardioprotective properties of the selected lignans related to their antioxidant and anti-inflammatory characteristis.
Assuntos
Lignanas , Schisandra , Schisandra/química , Frutas/química , Antioxidantes/farmacologia , Lignanas/farmacologia , Anti-Inflamatórios/farmacologiaRESUMO
BACKGROUND: Suanzaoren-Wuweizi herb-pair (SWHP), composed of Zizyphi Spinosi Semen (Suanzaoren in Chinese) and Schisandrae Chinensis Fructus (Wuweizi in Chinese), is a traditional herbal formula that has been extensively used for the treatment of insomnia. The study aimed to explore the targets and signal pathways of Suanzaoren-Wuweizi (S-W) in the treatment of anxiety by network pharmacology, and to verify the pharmacodynamics and key targets of SWHP in mice. METHODS: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) as well as literature mining were used to obtain the main chemical ingredients of Suanzaoren and Wuweizi. The SwissTargetPrediction platform was used to predict drug-related targets. The GeneCards, TTD, DisGeNET and OMIM databases were used to obtain potential targets for the treatment of anxiety with the chemical components of S-W. Drug-disease intersection genes were selected, and a protein-protein interaction (PPI) network was constructed using STRING. The core targets of S-W in the treatment of anxiety were selected according to the topological parameters, and GO functional enrichment as well as KEGG pathways enrichment analyses were performed for potential targets. The relationship network of the "drug-active ingredient-disease-target-pathway" was constructed through Cytoscape 3.8.0. The pharmacodynamics of SWHP in the treatment of anxiety was evaluated by the elevated plus maze (EPM), the light/dark box test (LDB) and the open field test (OFT). The mechanisms were examined by measuring monoamine neurotransmitters in brain of mice. RESULTS: The results showed that there were 13 active ingredients for the treatment of anxiety in the network. This includes sanjoinenine, swertisin, daucosterol, schizandrer B, wuweizisu C and gomisin-A. Additionally, there were 148 targets, such as AKT1, TNF, SLC6A4, SLC6A3, EGFR, ESR1, HSP90AA1, CCND1, and DRD2, mainly involved in neuroactive ligand-receptor interactions, the Serotonergic synapse pathway and the cAMP signaling pathway. After 1 week of treatment, SWHP (2 and 3 g/kg) induced a significant increase on the percentage of entries into and time spent on the open arms of the EPM. In the LDB test, SWHP exerted anxiolytic-like effect at 2 g/kg. In the open-field test, SWHP (2 g/kg) increased the number of central entries and time spent in central areas. The levels of brain monoamines (5-HT and DA) and their metabolites (5-HIAA, DOPAC) were decreased after SWHP treatment. CONCLUSIONS: The anti-anxiety effect of SWHP may be mediated by regulating 5-HT, DA and other signaling pathways. These findings demonstrated that SWHP produced an anxiolytic-like effect and the mechanism of action involves the serotonergic and dopaminergic systems, although underlying mechanism remains to be further elucidated.
Assuntos
Ansiolíticos , Schisandra , Animais , Camundongos , Ansiolíticos/farmacologia , Farmacologia em Rede , SerotoninaRESUMO
As a well-known traditional Chinese medicine and functional food, Schisandra chinensis (S. chinensis) has been proved to possess excellent neuroprotective effects, and particularly the role of the polysaccharide fraction in neuroprotection has been increasingly emphasized. The aim of this study was to investigate the therapeutic effects and potential mechanism of action of the homogeneous polysaccharide SCP2, isolated and purified from S. chinensis polysaccharide (SCP), on Alzheimer's disease (AD) rats based on a holistic metabolomics approach in serum and urine. The results of the pharmacodynamics study showed that SCP2 significantly improved Aß25-35-induced cognitive dysfunction, improved oxidative damage and reduced Aß deposition in the hippocampus. The holistic metabolomics results of serum and urine showed that the intervention with SCP2 significantly reversed the metabolic profile disorder in AD rats. A total of 40 metabolites (21 serum metabolites and 19 urine metabolites) were identified, which were mainly involved in linoleic acid metabolism, alpha-linolenic acid metabolism and arachidonic acid metabolism. The results obtained in this study will provide new insights into the mechanisms of SCP2 in the treatment of AD and provide a basis for the subsequent structure-activity studies of SCP2.
Assuntos
Doença de Alzheimer , Medicamentos de Ervas Chinesas , Schisandra , Animais , Ratos , Doença de Alzheimer/tratamento farmacológico , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/uso terapêutico , Metabolômica , Polissacarídeos/farmacologia , Ratos Sprague-Dawley , Espectrometria de MassasRESUMO
Plant extracts have been widely used for skin care for many centuries, and nowadays, they are commonly applied for the development and enrichment of new cosmetic preparations. The present study aimed the assessment of the biological activity of aqueous Schisandra chinensis extracts as a potential ingredient of skin care products. The aspects studied involved the ability to neutralize free radicals, impact on viability and metabolism of keratinocytes, as well as tyrosinase inhibitory potential. Our study showed that aqueous S. chinensis extracts have a positive effect on keratinocyte growth and have high antioxidant potential and strong tyrosinase inhibitory activity. UPLC-MS analysis revealed that three groups of phenolic compounds were predominant in the analyzed extract, including lignans, phenolic acids and flavonoids and protocatechiuc and p-coumaryl quinic acids were predominant. Moreover, microwave-assisted extraction, followed by heat reflux extraction, was the most effective for extracting polyphenols. Furthermore, a prototypical natural body washes gel formulation containing the previously prepared extracts was developed. The irritation potential and viscosity were assessed for each of the formulations. The study demonstrated that the addition of these extracts to body wash gel formulations has a positive effect on their quality and may contribute to a decrease in skin irritation. In summary, S. chinensis aqueous extracts can be seen as an innovative ingredient useful in the cosmetic and pharmaceutical industry.
Assuntos
Lignanas , Schisandra , Antioxidantes/farmacologia , Cromatografia Líquida , Monofenol Mono-Oxigenase , Espectrometria de Massas em Tandem , Extratos Vegetais/farmacologia , Lignanas/farmacologia , Higiene da PeleRESUMO
Based on the current results, they showed that Schisandra chinensis lignans (SCL) ameliorated depressive-like behaviors in chronic unpredictable mild stress (CUMS) mice, alleviated neuroinflammation, and improved neuronal injury. This study aimed to explore whether SCL exerted antidepressant effects through inhibiting neuroinflammation, in turn improving neuronal injury. In vitro studies revealed that SCL blocked lipopolysaccharide-increased BV2 microglial M1 but promoted the M2 phenotype. The BV2-N2a interaction model suggested that increasing the M2 phenotype of BV2 played neuroprotective effects. The current studies demonstrated that SCL up-regulated the expression of CUMS- and LPS-decreased cannabinoid receptor type-2 (CB2R) mRNA. In vitro studies showed that the transfection of BV2 with siCrn2 blocked the SCL-increased M2 phenotype via the inactivating signal transducer and activator of transcription 6 (STAT6) pathway, further decreasing the viability of N2a cells. Finally, the possible pharmacodynamic compounds, γ-schisandrin and schisantherin A, were indicated by AutoDuck analysis. Overall, our study showed that SCL promoted microglia polarization toward the M2 phenotype, in turn exerting neuroprotective effects by activating CB2R-STAT6 signaling further to play antidepressant roles.
