Résumé
OBJECTIVE@#To determine whether Schisandrin B (Sch B) attenuates early brain injury (EBI) in rats with subarachnoid hemorrhage (SAH).@*METHODS@#Sprague-Dawley rats were divided into sham (sham operation), SAH, SAH+vehicle, and SAH+Sch B groups using a random number table. Rats underwent SAH by endovascular perforation and received Sch B (100 mg/kg) or normal saline after 2 and 12 h of SAH. SAH grading, neurological scores, brain water content, Evan's blue extravasation, and terminal transferase-mediated dUTP nick end-labeling (TUNEL) staining were carried out 24 h after SAH. Immunofluorescent staining was performed to detect the expressions of ionized calcium binding adapter molecule 1 (Iba-1) and myeloperoxidase (MPO) in the rat brain, while the expressions of B-cell lymphoma 2 (Bcl-2), Bax, Caspase-3, nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), apoptosis-associated specklike protein containing the caspase-1 activator domain (ASC), Caspase-1, interleukin (IL)-1β, and IL-18 in the rat brains were detected by Western blot.@*RESULTS@#Compared with the SAH group, Sch B significantly improved the neurological function, reduced brain water content, Evan's blue content, and apoptotic cells number in the brain of rats (P<0.05 or P<0.01). Moreover, Sch B decreased SAH-induced expressions of Iba-1 and MPO (P<0.01). SAH caused the elevated expressions of Bax, Caspase-3, NLRP3, ASC, Caspase-1, IL-1β, and IL-18 in the rat brain (P<0.01), all of which were inhibited by Sch B (P<0.01). In addition, Sch B increased the Bcl-2 expression (P<0.01).@*CONCLUSION@#Sch B attenuated SAH-induced EBI, which might be associated with the inhibition of neuroinflammation, neuronal apoptosis, and the NLRP3 inflammatory signaling pathway.
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Animaux , Rats , Apoptose , Encéphale/anatomopathologie , Lésions encéphaliques/anatomopathologie , Caspase-3/métabolisme , Cyclooctanes , Bleu d'Evans , Inflammasomes/métabolisme , Interleukine-18/métabolisme , Lignanes , Protéine-3 de la famille des NLR contenant un domaine pyrine/métabolisme , Composés polycycliques , Protéines proto-oncogènes c-bcl-2/métabolisme , Rat Sprague-Dawley , Hémorragie meningée/traitement médicamenteux , Eau , Protéine Bax/métabolismeRésumé
In the current study, schisandrin B(SchB)-loaded F127 modified lipid-polymer hybrid nanoparticles(SchB-F-LPNs) were developed to improve the inhibition of breast cancer lung metastasis. Modified nanoprecipitation method was used to prepare SchB-F-LPNs. The nanoparticles were spherical in shape with shell-core structure by TEM observation. SchB-F-LPNs showed a mean particle size of(234.60±6.11) nm with zeta potential of(-5.88±0.49) mV. XRD results indicated that SchB existed in the nanoparticles in an amorphous state. The apparent permeability coefficient through porcine mucus of F-LPNs was 1.43-fold of that of LPNs as shown in the in vitro mucus penetration study. The pharmacokinetics study showed that the C_(max) of SchB was(369.06±146.94) μg·L~(-1),(1 121.34±91.65) μg·L~(-1) and(2 951.91±360.53) μg·L~(-1) respectively in SchB suspensions group, SchB-LPNs group and SchB-F-LPNs group after oral administration in rats. With SchB suspensions as the reference formulation, the relative bioavailability of SchB-F-LPNs was 568.60%. SchB-F-LPNs inhibited the morphological change during transforming growth factor-β1(TGF-β1)-induced epithelial-mesenchymal transition. In addition, SchB-F-LPNs significantly decreased the number of metastatic pulmonary nodules in 4 T1 tumor-bearing mice, suggesting that SchB-F-LPNs may inhibit the metastasis of breast cancer. These results reveal the promising potential of SchB-F-LPNs in treatment of breast cancer lung metastasis.
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Animaux , Souris , Rats , Cyclooctanes , Lignanes , Lipides , Tumeurs du poumon/traitement médicamenteux , Nanoparticules , Composés polycycliques , Polyéthylènes , Polymères , Polypropylènes , SuidaeRésumé
Malignant melanoma (MM) is one of the malignant tumors with highly metastatic and aggressive biological actions. Schizandrin A (SchA) is a bioactive lignin compound with strong anti-oxidant and anti-aging properties, which is stable at room temperature and is often stored in a cool dry place. Hence, we investigated the effects of SchA on MM cell line A375 and its underlying mechanism. A375 cells were used to construct an in vitro MM cell model. Cell viability, proliferation, apoptosis, and migration were detected by Cell Counting Kit-8, BrdU assay, flow cytometry, and transwell two-chamber assay, respectively. The cell cycle-related protein cyclin D1 and cell apoptotic proteins (Bcl-2, Bax, cleaved-caspase-3, and cleaved-caspase-9) were analyzed by western blot. Alteration of H19 expression was achieved by transfecting with pEX-H19. PI3K/AKT pathway was measured by detecting phosphorylation of PI3K and AKT. SchA significantly decreased cell viability in a dose-dependent manner. Furthermore, SchA inhibited cell proliferation and cyclin D1 expression. SchA increased cell apoptosis along with the up-regulation of pro-apoptotic proteins (cleaved-caspase-3, cleaved-caspase-9, and Bax) and the down-regulation of anti-apoptotic protein (Bcl-2). Besides, SchA decreased migration and down-regulated matrix metalloproteinases (MMP)-2 and MMP-9. SchA down-regulated lncRNA H19. Overexpression of H19 blockaded the inhibitory effects of SchA on A375 cells. SchA decreased the phosphorylation of PI3K and AKT while H19 overexpression promoted the phosphorylation of PI3K and AKT. SchA inhibited A375 cell growth, migration, and the PI3K/AKT pathway through down-regulating H19.
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Humains , Composés polycycliques/pharmacologie , Régulation négative/effets des médicaments et des substances chimiques , Mouvement cellulaire/effets des médicaments et des substances chimiques , Apoptose/effets des médicaments et des substances chimiques , Lignanes/pharmacologie , Cyclooctanes/pharmacologie , Prolifération cellulaire/effets des médicaments et des substances chimiques , Mélanome/anatomopathologie , Transduction du signal/effets des médicaments et des substances chimiques , Régulation de l'expression des gènes tumoraux/effets des médicaments et des substances chimiques , Technique de Western , microARN/métabolisme , Lignée cellulaire tumorale , Réaction de polymérisation en chaine en temps réel , ARN long non codantRésumé
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.
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Animaux , Comportement animal , Caenorhabditis elegans , Agents du système nerveux central , Chimie , Pharmacologie , Cyclooctanes , Pharmacologie , Médicaments issus de plantes chinoises , Chimie , Pharmacologie , Lignanes , Pharmacologie , Extraits de plantes , Chimie , Pharmacologie , Composés polycycliques , Pharmacologie , Schisandra , Chimie , Danio zébré , PhysiologieRésumé
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.
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Animaux , Comportement animal , Caenorhabditis elegans , Agents du système nerveux central , Chimie , Pharmacologie , Cyclooctanes , Pharmacologie , Médicaments issus de plantes chinoises , Chimie , Pharmacologie , Lignanes , Pharmacologie , Extraits de plantes , Chimie , Pharmacologie , Composés polycycliques , Pharmacologie , Schisandra , Chimie , Danio zébré , PhysiologieRésumé
The stereochemistry of two 6, 9-oxygen bridge dibenzocyclooctadiene lignans from Kadsura coccinea, are difficult to separate and very unstable. The present study was designed to develop a high-performance liquid chromatography using circular dichroism detection for the analysis of the stereochemistry. A new 6, 9-oxygen bridge dibenzocyclooctadiene lignans named Kadsulignan Q was firstly found with an S-biphenyl configuration. The other compound was identified as Kadsulignan L with an R- biphenyl configuration. In order to obtain kinetic data on their reversible interconversion, the stability was measured at different deuterated solvents such as deuterated methanol, deuterated chloroform and deuterated dimethylsulfoxide. The lignans were more unstable and converted more easily in deuterated methanol than in deuterated chloroform and deuterated dimethylsulfoxide.
Sujets)
Chromatographie en phase liquide à haute performance , Dichroïsme circulaire , Cyclooctanes , Chimie , Kadsura , Chimie , Lignanes , Chimie , Structure moléculaire , Oxygène , Extraits de plantes , Chimie , StéréoisomérieRésumé
AIM@#To illuminate the molecular targets for schisandrin against cerebrovascular disease based on the combined methods of network pharmacology prediction and experimental verification.@*METHOD@#A protein database was established through constructing the drug-protein network from literature mining data. The protein-protein network was built through an in-depth exploration of the relationships between the proteins. The computational platform was implemented to predict and extract the sensitive sub-network with significant P-values from the protein-protein network. Then the key targets and pathways were identified from the sensitive sub-network. The most related targets and pathways were also confirmed in hydrogen peroxide (H2O2)-induced PC12 cells by Western blotting.@*RESULTS@#Twelve differentially expressed proteins (gene names: NFKB1, RELA, TNFSF10, MAPK1, CHUK, CASP8, PIGS2, MAPK14, CREB1, IFNG, APP, and BCL2) were confirmed as the central nodes of the interaction network (45 nodes, 93 edges). The NF-κB signaling pathway was suggested as the most related pathway of schisandrin for cerebrovascular disease. Furthermore, schisandrin was found to suppress the expression and phosphorylation of IKKα, as well as p50 and p65 induced by H2O2 in PC12 cells by Western blotting.@*CONCLUSION@#The computational platform that integrates literature mining data, protein-protein interactions, sensitive sub-network, and pathway results in identification of the NF-κB signaling pathway as the key targets and pathways for schisandrin.
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Animaux , Humains , Rats , Angiopathies intracrâniennes , Traitement médicamenteux , Génétique , Métabolisme , Cyclooctanes , Pharmacologie , Médicaments issus de plantes chinoises , Pharmacologie , Réseaux de régulation génique , Lignanes , Pharmacologie , Thérapie moléculaire ciblée , Cellules PC12 , Composés polycycliques , Pharmacologie , Cartes d'interactions protéiques , Transduction du signalRésumé
A set of central composite design experiments were designed by using four factors which were ethanol amount, ethanol concentration, refrigeration temperature and refrigeration time. The relation between these factors with the target variables of the retention rate of schizandrol A, the soluble solids content, the removal rate of fructose and the removal rate of glucose were analyzed with Bayesian networks, and ethanol amount and ethanol concentration were found as the critical process parameters. Then a network model was built with 2 inputs and 4 outputs using back propagation artificial neural networks which was optimized by genetic algorithms. The R2 and MSE from the training set were 0.983 8 and 0.001 1. The R2 and MSE from the test set were 0.975 9 and 0.001 8. The results showed that network analysis method could be used for modeling of Schisandrae Chinensis Fructus ethanol precipitation process and identify critical operating parameters.
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Théorème de Bayes , Précipitation chimique , Basse température , Cyclooctanes , Chimie , Éthanol , Chimie , Fructose , Fruit , Chimie , Glucose , Lignanes , Chimie , , Composés polycycliques , Chimie , Reproductibilité des résultats , Schisandra , Chimie , Facteurs tempsRésumé
A new dibenzocyclooctadiene lignan, renchangianin E (1) was isolated from the stems of Kadsura renchangiana. Its structure and stereochemistry were elucidated by spectroscopic methods, including 2D-NMR techniques.
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Cyclooctanes , Chimie , Kadsura , Chimie , Lignanes , Chimie , Spectroscopie par résonance magnétique , Structure moléculaireRésumé
In this study, it is to compare the effectiveness of prevention against and treatment of doxorubicin (DOX) induced cardiotoxicity by dexrazoxane and schisandrin B (Sch B) in rats. Sprague-Dawley (SD) rats were randomly divided into the following 6 groups: normal saline group, DOX group, DOX+DEX group, DOX+Sch B (80 mg x kg(-1)) group, DOX+Sch B (40 mg x kg(-1)) group and DOX+Sch B (20 mg x kg(-1)) group. The results showed that Sch B could combat the increase of myocardial enzymes in peripheral blood, decrease of the enzyme activity of myocardial tissue antioxidant enzymes and disorders of systolic and diastolic function of heart in rats intravenously injected with doxorubicin (15 mg x kg(-1)). Sch B was better than DEX in protecting rat against DOX-induced the symptoms. Sch B could protect rat against DOX-induced acute cardiomyopathy and has clinical potential applications.
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Animaux , Rats , Antibiotiques antinéoplasiques , Antioxydants , Métabolisme , Cardiomyopathies , Traitement médicamenteux , Cardiotoxicité , Traitement médicamenteux , Cyclooctanes , Utilisations thérapeutiques , Dexrazoxane , Utilisations thérapeutiques , Doxorubicine , Coeur , Lignanes , Utilisations thérapeutiques , Myocarde , Composés polycycliques , Utilisations thérapeutiques , Rat Sprague-DawleyRésumé
To establish a method for determination contents of schizandrin, tanshinone I, cryptotanshinone, tanshinone II (A) and schizandrin B in rongxin pills. The HPLC method was performed on an Agilent C18. The mobile phase was composed of methnol and water wish gradient elution. The flow rate was 1.0 mL x min(-1). The column temperature was 30 degrees C and the detection wavelength wash 240 nm. The linear of schizandrin, tanshinone I, cryptotanshinone, Tanshinone II (A) and schizandrin B were 3.000-48.00 (r = 1.000), 3.985-63.76 (r = 0.999 9), 6.370-101.9 (r = 1.000), 8.690-139.0 (r = 0.999 9), 1.700-27.20 mg x L(-1) (r = 0.999 9), respectively. The average recoveries were 98.44%, 100.3%, 99.29%, 99.07%, 98.42%, and RSDs were 0.61%, 1.1%, 0.52%, 0.72%, 0.97%. The method is convenient, accurate and has good precision. It can be used for determination of the preparation.
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Chromatographie en phase liquide à haute performance , Cyclooctanes , Abiétanes , Médicaments issus de plantes chinoises , Chimie , Lignanes , Modèles linéaires , Composés chimiques organiques , Phénanthrènes , Composés polycycliques , Contrôle de qualité , Reproductibilité des résultatsRésumé
The effect of plant growth regulator forchlorfenuron (CPPU) 1 x 10(-6), 0.67 x 10(-6), 0.5 x 10(-6) on fruit morphology and effective components lignans was studied. Those morphologies were the combination of four basic morphological changes. The result showed, diametre were increased and longitudinal diametre of fruits were inhibited by foliage fertilizers including CPPU. At the same time, 1 000-grain weight and yield showed the varying degrees increase under CPPU. The order of the degree was 0.5 x 10(-6) > 1 x 10(-6) > 0.67 x 10(-6). Six lignans content of Schisandra chinensis of different harvest time and different CPPU processing groups were determined, the results showed that lignans accumulation occurred mainly in periods of premature the half mature fruiting stages. Under the 0.67 x 10(-6) CPPU treatment, schisandrol B, schisandrin B, schisandrin C content of S. chinensis showed different increase.
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Chromatographie en phase liquide à haute performance , Cyclooctanes , Métabolisme , Dioxoles , Métabolisme , Relation dose-effet des médicaments , Fruit , Métabolisme , Lignanes , Métabolisme , Phénylurées , Pharmacologie , Composés polycycliques , Métabolisme , Pyridines , PharmacologieRésumé
High-speed counter-current chromatography (HSCCC) was used to high performance separate and prepare lignans from Schisandrae chinensis fructus. The solvent system is composed of n-hexane-ethyl acetate-methanol-water (9 : 1 : 5 : 5) and n-hexane-ethyl acetate-methanol-water (9 : 1 : 9 : 5), speed is at 900 r.min-1, and flow rate is at 2.0 mL.min-1. Five fractions from Schisandrae chinensis fructus extract were separated and prepared with one HSCCC process. They were identified as schisandrin, gomisin J, schisandrol B, schisantherin A and deoxyschizandrin by electrospray ionization-multiple tandem mass spectrometry (ESI-MSn), respectively. Their contents were obtained in 98.74%, 94.32%, 99.53%, 94.23% and 98.68% by ultra high performance liquid chromatography (UPLC), separately. The rapid and simple method can be applied for the preparation of lignans from Schisandrae chinensis fructus.
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Distribution à contre-courant , Cyclooctanes , Chimie , Dioxoles , Chimie , Médicaments issus de plantes chinoises , Chimie , Fruit , Chimie , Lignanes , Chimie , Structure moléculaire , Plantes médicinales , Chimie , Composés polycycliques , Chimie , Schisandra , Chimie , Spectrométrie de masse ESI , Spectrométrie de masse en tandemRésumé
It is valuable to establish a chemical-pharmacokinetic (PK)-pharmacodynamics (PD) fingerprint of traditional Chinese medicine (TCM) for comprehensively understanding the TCM integrated conception and revealing the material foundation. The chemical, metabolic in vitro, and PK/PD in vivo fingerprints of Schisandra chinensis (SC) alcoholic extract were established and comparatively analyzed using HPLC-UV-MS method, rat liver microsomes in vitro and CCl4 intoxicated rats in vivo. Four known effective lignans, schisandrin, schisantherin A, deoxyschizandrin and gamma-schisandrin, were detected as the standard references in SC alcoholic extract with high concentration. SC alcoholic extract and four lignans when incubated with rat liver microsomes produced several metabolites in NAPDH-dependent manner. Chemical fingerprint of some components with bioactivities were also identified in PK and PD fingerprints in normal and ALI rats that explained the material foundation of SC alcoholic extract for multiple pharmacological effects. Schisandrin, schisantherin A, deoxyschizandrin and gamma-schisandrin could be considered as the "PK marker" of SC alcoholic extract or its relevant preparations, while two metabolites of the four lignans, 7, 8-dihydroxy-schizandrin and another one (M(W) 432), could be recognized as drug-metabolism (DM) Marker. This work provides experimental data for the further studies of metabolism or material foundation of SC components.
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Animaux , Mâle , Rats , Alanine transaminase , Sang , Intoxication au tétrachlorure de carbone , Lésions hépatiques dues aux substances , Sang , Chromatographie en phase liquide à haute performance , Cyclooctanes , Pharmacocinétique , Pharmacologie , Médicaments issus de plantes chinoises , Pharmacocinétique , Pharmacologie , Lignanes , Pharmacocinétique , Pharmacologie , Microsomes du foie , Métabolisme , Plantes médicinales , Chimie , Composés polycycliques , Pharmacocinétique , Pharmacologie , Répartition aléatoire , Rat Sprague-Dawley , Schisandra , Chimie , Spectrométrie de masse ESI , Spectrophotométrie UVRésumé
<p><b>OBJECTIVE</b>To investigate the pharmacokinetic interaction among three major bioactive compounds of Shengmai formula.</p><p><b>METHODS</b>After oral administration of ginsenoside Rg(1), ginsenoside Rb(1) and schisandrin with the same dose(100 mg.kg(-1)) individually or in combination, rat serum samples were extracted, then these three compounds were determined by liquid chromatography-mass spectrometry(LC-MS). The pharmacokinetic parameters of three compounds in single or combination form were calculated by WinNonLinu6.0 using non-compartment model.</p><p><b>RESULTS</b>Compared with single drug group, the peak concentration of ginsenoside Rg(1) in combined group increased from(0.476 ±0.238) μg.ml(-1) to (1.946 ±1.432) μg.ml(-1), AUC(0-∞) increased from(0.523 ±0.238) μg.h.ml(-1) to (1.908 ±1.319) μg.h.ml(-1), CL decreased from(226311 ± 96819) ml.h(-1).kg(-1) to(90650 ±73684) ml.h(-1).kg(-1) and Vd decreased from(317110 ±154009) ml.kg(-1) to(130967 ±78306) ml.kg(-1). While the pharmacokinetic parameters of ginsenoside Rb(1) and schisandrin showed no significant change.</p><p><b>CONCLUSION</b>Combined oral administration of three compounds of Shengmai formula can improve the bioavailability of ginsenoside RgRg(1), however it does not change the pharmacokinetic behavior of ginsenoside RbRg(1) and schisandrin.</p>
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Animaux , Mâle , Rats , Biodisponibilité , Chromatographie en phase liquide , Cyclooctanes , Sang , Pharmacocinétique , Synergie des médicaments , Ginsénosides , Sang , Pharmacocinétique , Lignanes , Sang , Pharmacocinétique , Composés polycycliques , Sang , Pharmacocinétique , Rat Sprague-Dawley , Spectrométrie de masse en tandemRésumé
The aim of the study is to establish a new method of quality evaluation and validate its feasibilities by the simultaneous quantitative assay of four lignanoids in Schisandra chinensis. A new quality evaluation method, quantitative analysis of multi-components by single marker (QAMS), was established and validated with Schisandra chinensis. Four main lignanoids, schisandrin, schisantherin A, deoxyschizandrin and gamma-schizandrin, were selected as analytes and schisandrin as internal reference substance to evaluate the quality. Their contents in 13 different batches of samples, collected from different bathes, were determined by both external standard method and QAMS. The method was evaluated by comparison of the quantitative results between external standard method and QAMS. No significant differences were found in the quantitative results of four lignanoids in 13 batches of S. chinensis determined by external standard method and QAMS. QAMS is feasible for determination of four lignanoids simultaneously when some authentic standard substances were unavailable, and the developed method can be used for quality control of S. chinensis.
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Chromatographie en phase liquide à haute performance , Méthodes , Cyclooctanes , Dioxoles , Médicaments issus de plantes chinoises , Chimie , Fruit , Chimie , Lignanes , Plantes médicinales , Chimie , Composés polycycliques , Contrôle de qualité , Schisandra , ChimieRésumé
This study is to investigate the protection effect of schisandrin B (Sch B) against oxidation stress of HK-2 cells induced by cisplatin and the mechanisms involved. HK-2 cells were cultured and divided into different groups: solvent control group, cisplatin exposure group, positive group, Sch B treatment group. Cell viability and toxicity were evaluated by MTT and LDH assay. GSH level and SOD enzymes activities were also measured. DCFH-DA as fluorescence probe was used to detect ROS level by fluorescence microplate reader. Nrf2 translocation was detected by Western blotting. Real time Q-PCR was used to detect expressions of NQO1, HO-1 and GCLC mRNA level. The results showed that Sch B could significantly inhibit the decline of cell viability induced by cisplatin treatment (P < 0.05) and the protective effect was in a dose dependent manner. Furthermore, Sch B treatment significantly inhibited the increase of ROS level induced by cisplatin and reversed the decrease of GSH level (P < 0.05). When Sch B concentration was up to 5 micromol x L(-1), SOD enzyme activities were also enhanced significantly compared with that of the cisplatin group (P < 0.05). It was shown that Sch B could cause nuclear accumulation of Nrf2 in association with downstream activation of Nrf2 mediated oxidative response genes such as GCLC, NQO1 and HO-1. These results suggested Sch B could protect against the oxidative damage of HK-2 cells induced by cisplatin via the activation of Nrf2/ARE signal pathway.
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Humains , Antinéoplasiques , Toxicité , Antioxydants , Pharmacologie , Lignée cellulaire , Survie cellulaire , Cisplatine , Toxicité , Cyclooctanes , Pharmacologie , Glutamate-cysteine ligase , Génétique , Métabolisme , Glutathion , Métabolisme , Heme oxygenase-1 , Génétique , Métabolisme , Tubules contournés proximaux , Biologie cellulaire , Métabolisme , L-Lactate dehydrogenase , Métabolisme , Lignanes , Pharmacologie , NADPH dehydrogenase (quinone) , Génétique , Métabolisme , Facteur-2 apparenté à NF-E2 , Génétique , Métabolisme , Composés polycycliques , Pharmacologie , ARN messager , Métabolisme , Espèces réactives de l'oxygène , Métabolisme , Schisandra , Chimie , Transduction du signal , Superoxide dismutase , MétabolismeRésumé
<p><b>OBJECTIVE</b>To investigate the role of Fas pathway in H(2)O(2)-induced apoptosis of L02 human hepatocytes and the effect of schisandrin B on Fas pathway.</p><p><b>METHODS</b>Real-time quantitative PCR was used to detect the expressions of FAS, fas associated death domain protein (FADD) and caspase-8 mRNA in L02 cells exposed to H(2)O(2). Flow cytometry was employed to assess the cell apoptosis. ELISA, Western blotting and spectrophotometric assay were performed to determine the expressions of FAS protein, FADD protein and caspase-8 activity.</p><p><b>RESULTS</b>Within the dose range of 5-15 mol/L, schisandrin B dose-dependently inhibited FAS and FADD expressions and caspase-8 activation.</p><p><b>CONCLUSION</b>Schisandrin B can partially inhibit H(2)O(2)-induced L02 cell apoptosis possibly by affecting the FAS-FADD-caspase-8 pathway.</p>
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Humains , Apoptose , Caspase 8 , Métabolisme , Lignée cellulaire , Cyclooctanes , Pharmacologie , Protéine à domaine de mort associée à Fas , Métabolisme , Cytométrie en flux , Hépatocytes , Métabolisme , Peroxyde d'hydrogène , Lignanes , Pharmacologie , Composés polycycliques , Pharmacologie , Transduction du signal , Antigènes CD95 , MétabolismeRésumé
<p><b>OBJECTIVE</b>To investigate the effects of schisandrin B (Sch-B) on expression of transforming growth factor-beta1 (TGF-beta1) and signal transduction molecule mRNA in rat lungs exposed to SiO2, and explore the intervention mechanism of Sch-B on pulmonary fibrosis induced by SiO2.</p><p><b>METHODS</b>Ninety six Wistar rats were randomly divided into control (normal saline) group, SiO2 group and SiO2 plus Sch-B group. The rats were exposed to SiO2 by direct tracheal instillation to establish the silicotic animal models. SiO2 group and SiO2 plus Sch-B group were treated with 1 ml SiO2 (50 mg/ml) for each rat From the first day after model establishment, SiO2 plus Sch-B group were orally given Sch-B (80 mg/kg) a day, control group and silica group were orally given olive oil. On the 3rd, 7th, 14th and 28th days after treatment, 8 rats in each group were sacrificed and samples were collected. The histo-pathological examination of lung was performed by HE staining. The expression levels of TGF-beta1, TGF-betaR II and Smad4 mRNA in the lung tissues were detected by RT-PCR.</p><p><b>RESULTS</b>The results of histo-pathological examination showed that in SiO2 group, lung tissues were injured obviously; the alveolar inflammation with alveolus interval edema and inflammation cell infiltration appeared on the 3rd and 7th days; the alveolus interval became thicker, became thicker, fibroblast and collagen matrix increased markedly on 14th day; the alveolar structure was damaged, alveolar wall thickened obviously, collagen aggravation and pulmonary fibrosis displayed on 28th day. The alveolar inflammation and pulmonary fibrosis in SiO2 plus Sch-B group were significantly less than those in SiO2 group. The expressions levels of TGF-beta1 TGF-betaR II and Smad4 mRNA (TGF-1beta: 1.03 +/- 0.31, 1.33 +/- 0.39,1.08 +/- 0.26, 0.82 +/- 0.16, TGF-betaR II: 0.65 +/- 0.11, 0.80 +/- 0.16, 0.83 +/- 0.24, 0.62 +/- 0.15, Smad4:0.87 +/- 0.15, 0.68 +/- 0.11, 0.78 +/- 0.19, 0.30 +/- 0.08) in SiO2 group were significantly higher than those in the control group (TGF-beta1:0.59 +/- 0.22, 0.55 +/- 0.25, 0.56 +/- 0.20, 0.55 +/- 0.12, TGR-betaR II :0.28 +/- 0.13, 0.31 +/- 0.15, 0.34 +/- 0.15, 0.27 +/- 0.09, Smad4:0.23 +/- 0.11, 0.40 +/- 0.12, 0.39 +/- 0.12, 0.18 +/- 0.06) (P < 0.01 or P < 0.05), but the expression level of TGF-beta1 mRNA was the highest on the 7th day. The expression levels of TGF-beta1 and Smad4 mRNA (TGF-beta1:0.68 +/- 0.28, 0.88 +/- 0.25, 0.75 +/- 0.11, 0.61 +/- 0.14,Smad4:0.25 +/- 0.12, 0.45 +/- 0.09, 0.44 +/- 0.07, 0.21 +/- 0.04) in SiO2 plus Sch-B group were significantly lower than those in SiO2 group (P < 0.01 or P < 0.05 ), but there were no significant differences of the TGFbetaR II mRNA expression levels between SiO2 group and SiO2 plus Sch-B group.</p><p><b>CONCLUSION</b>Sch-B can reduce the pulmonary fibrosis induced by SiO2 through inhibition of the mRNA express of TGF-beta1 and Smad4 in the lung tissue, modulating the TGF-beta1/Smad4 signal transduction pathway and inhibiting the target gene activation.</p>
Sujets)
Animaux , Femelle , Mâle , Rats , Cyclooctanes , Pharmacologie , Lignanes , Pharmacologie , Poumon , Métabolisme , Anatomopathologie , Composés polycycliques , Pharmacologie , ARN messager , Génétique , Rat Wistar , Transduction du signal , Silicose , Métabolisme , Anatomopathologie , Protéine Smad-4 , Génétique , Métabolisme , Facteur de croissance transformant bêta-1 , Génétique , MétabolismeRésumé
<p><b>OBJECTIVE</b>To observe the effects of schizandrins on the learning and memory disorder in mice, and explore its mechanism.</p><p><b>METHOD</b>The memory impairment model was established by using the pentobarbital sodium (20 mg x kg(-1)) intraperitoneally injected in mice. Schizandrins (0.5, 1.0, 2.0 g x kg(-1)) were administered through intragavage for consecutive 14 days. Morris Water Maze test was used to evaluate the impairment of learning and memory. The energy of superoxide dismutase (SOD), nitric oxide (NO) and catalase (CAT) of brain tissue were measured. And the positive expression of nuclear transcription factor-kappaB p65 (NF-kappaB p65), caspase-3 in the hippocampus CA1 region were determined by immunohistochemical analysis. At the cellular level, 24 h after schizandrins (0.062 5, 0.125, 0.25 g x L(-1)) were pre-administered, the apoptosis model of PC12 cell was induced by H2O2, and activity of PC12 cell was detected by MTT colorimetric assay, the energy of NO in cell serum were measured. The expression of Bcl-2 was determined by the combination of immunocytochemical staining and image analysis software.</p><p><b>RESULT</b>Morris Water Maze test showed that the model group mice took shorter searching time and distance on the previous flat area than those in the control group (P < 0.05), which could be prolonged after schizandrins treatment (P < 0.05, P < 0.01). Compared with the control group, the level of NO increased while the activity of SOD, CAT decreased in the model group (both P < 0.01). After treated with schizandrins, the level of NO significantly decreased (P < 0.01), while the activity of SOD increased (P < 0.01). Immunohistochemistry analysis showed that the protein expression of NF-kappaB p65, Caspase-3 in the hippocampal CA1 region significantly increased after modeling, while schizandrins (1.0 g x kg(-1)) can significantly inhibit the protein expression of NF-kappaB p65, Caspase-3 (P < 0.05, P < 0.01). Compared with the H2O2, model group, schizandrins (0.125, 0.25 g x L(-1)) can significantly increased PC12 cell activity and decreased the NO level (P < 0.05, P < 0.01), the expression of Bcl-2 in the schizandrins group (0.125, 0.25 g x L(-1)) was up-regulated.</p><p><b>CONCLUSION</b>Schizandrins could improve the learning-memory dysfunction induced by the sodium pentobarbital in mice, and its protective mechanism is related to the lowering oxidative damage and inhibiting the cell apoptosis through up-regulating the expression of Bcl-2.</p>