RÉSUMÉ
Current guidelines give priority to surgical treatment of carotid artery stenosis (CAS) before coronary artery bypass grafting (CABG), especially in symptomatic patients. Carotid artery stenting is an alternative treatment for narrowing of the carotid arteries. This study sought to demonstrate the role of severe CAS in predicting stroke after CABG and assess the efficacy of carotid artery stenting in preventing postoperative stroke in a Chinese cohort. From 2015 to 2021, 1799 consecutive patients undergoing isolated CABG surgery were retrospectively recruited in a Chinese cohort. The predictive value of severe CAS in postoperative stroke and carotid stenting in preventing postoperative stroke was statistically analyzed. The incidence of postoperative stroke was 1.67%. The incidence of CAS with stenosis ≥ 50% and ≥ 70% was 19.2% and 6.9%. After propensity matching, the incidence of stroke was 8.0% in the severe CAS group and 0% in the non-severe CAS group. We successfully established an optimal predictive nomogram for predicting severe CAS in patients undergoing CABG. Carotid artery stenting was found ineffective in preventing postoperative stroke. The present study provides the incidence of CAS and postoperative stroke in a Chinese cohort, identifies severe CAS as an independent risk factor for postoperative stroke after CABG, constructs a nomogram predicting the incidence of severe CAS, and evaluates the effectiveness of carotid artery stenting in preventing postoperative stroke after CABG.
Sujet(s)
Sténose carotidienne , Maladie des artères coronaires , Endartériectomie carotidienne , Accident vasculaire cérébral , Humains , Sténose carotidienne/chirurgie , Sténose carotidienne/complications , Maladie des artères coronaires/complications , Études de cohortes , Études rétrospectives , Peuples d'Asie de l'Est , Résultat thérapeutique , Endoprothèses/effets indésirables , Pontage aortocoronarien/effets indésirables , Accident vasculaire cérébral/épidémiologie , Accident vasculaire cérébral/étiologie , Facteurs de risque , Endartériectomie carotidienne/effets indésirablesRÉSUMÉ
OBJECTIVE: Long noncoding RNA WDFY3-AS2 has been shown to play dual roles in the modulation of cancer progression. This study aimed at clarifying the biological role of WDFY3-AS2 as well as the association between WDFY3-AS2 expression, ß-catenin expression, and OSCC immunity in oral squamous cell carcinoma (OSCC). DESIGN: Bioinformatics analyses, CCK8, EdU, wound healing, transwell, RT-qPCR, western blot, immunofluorescence, in situ hybridization, and immunohistochemistry assays were adopted for exploring the role of WDFY3-AS2 in OSCC. RESULTS: Bioinformatics analyses showed that WDFY3-AS2 conferred a poor prognosis for OSCC patients. Further analyses identified WDFY3-AS2 as an independent prognostic indicator for OSCC. Moreover, silencing WDFY3-AS2 inhibits OSCC cell proliferation, migration and invasion. Gene set enrichment analysis indicated that WDFY3-AS2 participated in the regulation of Wnt signaling. In addition, WDFY3-AS2 expression was positively associated with ß-catenin mRNA levels, the key component of Wnt signaling. Interestingly, WDFY3-AS2 knockdown inhibited ß-catenin expression and nuclear translocation, thus suppressing OSCC progression through Wnt signaling. Furthermore, WDFY3-AS2 expression correlated with an immunosuppressive phenotype in the tumor immune microenvironment. In situ hybridization and immunohistochemistry verified that WDFY3-AS2 was positively associated with total and nuclear ß-catenin protein levels and negatively associated with CD4 expression. CONCLUSIONS: This study demonstrates that the immunity-associated WDFY3-AS2 augments OSCC proliferation and metastasis through Wnt/ß-catenin signaling and may serve as a novel treatment target and a new prognostic factor for OSCC.
Sujet(s)
Carcinome épidermoïde , Tumeurs de la tête et du cou , Tumeurs de la bouche , ARN long non codant , Humains , Protéines adaptatrices de la transduction du signal/métabolisme , Protéines associées à l'autophagie/génétique , Protéines associées à l'autophagie/métabolisme , bêta-Caténine/métabolisme , Carcinome épidermoïde/génétique , Carcinome épidermoïde/anatomopathologie , Lignée cellulaire tumorale , Mouvement cellulaire/génétique , Prolifération cellulaire/génétique , Régulation de l'expression des gènes tumoraux , Tumeurs de la tête et du cou/génétique , Tumeurs de la bouche/anatomopathologie , ARN long non codant/génétique , ARN long non codant/métabolisme , Carcinome épidermoïde de la tête et du cou/génétique , Microenvironnement tumoral , Voie de signalisation Wnt/physiologieRÉSUMÉ
Anwulignan (AN) is a monomer lignan from Schisandra sphenanthera Rehd. et Wits (Schisandra sphenanthera fructus, Schisandra sphenanthera). The protective effect of AN against the indomethacin (IND)-induced gastric injury to mice and the related mechanism of action was investigated in this study. The effect of AN was mainly assessed by observing the gastric tissue morphology, gastric ulcer index (GUI), ulcer inhibition rate (UIR), gastric juice volume (GJV) and pH value. Chemical colorimetry, immunofluorescence, ELISA, and Western blot were used to detect related factors in the gastric tissue. The results showed that AN reduced the GUI, increased the UIR, inhibited the GJV, and increased the gastric pH value. AN significantly increased cyclooxygenase-1, cyclooxygenase-2, and prostaglandin E2 expression levels in the gastric tissue, activated nuclear factor (erythroid-derived 2)-like 2 (Nrf2), increased heme oxygenase-1 expression, enhanced the activity of superoxide dismutase and glutathione peroxidase, and decreased the malondialdehyde content. AN reduced the phosphorylation of nuclear factor-κ gene binding (NF-κB) p65 and its nuclear translocation, the key protein of NF-κB signaling pathway in the gastric tissue, and the content of the pathway downstream signaling molecules, including interleukin-6, interleukin-1ß, and tumor necrosis factor-α, to play an anti-inflammatory role. AN inhibited the downstream signals B-cell lymphoma 2-associated x protein and cleaved caspase-3 in gastric tissue, and activated B-cell lymphoma 2, to play an antiapoptotic role, which were further verified by Hoechst staining. Therefore, AN has a significant protection against the gastric injury induced by IND in mice, and the mechanism may be concerned in its activation of Nrf2, inhibition of NF-κB signaling pathway, and anti-apoptotic effect. SIGNIFICANCE STATEMENT: Anwulignan (AN) significantly reduced the indomethacin-induced gastric injury in mice, and its antioxidation, anti-inflammation, and antiapoptosis were considered to be involve in the effect, suggesting that AN should be a potential drug or food supplement for gastric injury induced by indomethacin.
Sujet(s)
Lignanes , Facteur-2 apparenté à NF-E2 , Animaux , Anti-inflammatoires/pharmacologie , Anti-inflammatoires/usage thérapeutique , Caspase-3 , Cyclooxygenase 1 , Cyclooxygenase 2 , Dinoprostone , Glutathione peroxidase , Heme oxygenase-1/métabolisme , Indométacine , Interleukine-1 bêta/génétique , Interleukine-6 , Malonaldéhyde/métabolisme , Souris , Facteur-2 apparenté à NF-E2/métabolisme , Facteur de transcription NF-kappa B/métabolisme , Protéines proto-oncogènes c-bcl-2 , Superoxide dismutase/métabolisme , Facteur de nécrose tumorale alpha/métabolismeRÉSUMÉ
Anwulignan is a representative component of Chinese traditional medicine Schisandra sphenanthera, with strong pharmacological activities. However, there are few reports on its pharmacokinetics and metabolites in the body. In this study, a metabolomic method based on UHPLC-Q-Orbitrap-MS was used to study the pharmacokinetics of anwulignan in the blood, organs, urine, and feces samples of mice after the intragastric administration of anwulignan (10 mg/kg). The pharmacokinetic parameters were calculated, and the distribution characteristics and main metabolites of anwulignan in the body of mice were analyzed. The results showed that the retention time of anwulignan in the body of mice was longer (t 1/2 = 7.1 h), and anwulignan was widely distributed in the body (Vz/F = 32.81 L/kg), especially in the liver. The order of anwulignan concentration in the tissues of mice from high to low was the liver > heart > brain > kidney > lung > spleen. Anwulignan was mainly excreted through the digestive tract in the form of its prototype and metabolites, indicating that it might experience an enterohepatic circulation. A total of seven metabolites were identified, and the demethylation, hydroxylation, dehydroxylation, and demethoxylation were considered to be the main metabolic ways of anwulignan in the body of mice.
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The aim of this study was to investigate the hepatoprotection of Schisandra chinensis Caulis polysaccharides (SCPs) in the nonalcoholic fatty liver disease (NAFLD) induced by high-fat diet (HFD) in rats. A total of 30 Wistar rats were randomly divided into the control group (CON), model group (MOD), and Schisandra chinensis caulis polysaccharide (SCP) group. Except for those in the CON group, the other rats were fed with high-fat diet for 4 weeks to establish an NAFLD model. From the 5th week, rats in the SCP group were given SCP solution (100 mg kg-1) by gavage for 6 weeks, and those in the CON and MOD groups were given an equal volume of distilled water in the same way. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) levels in serum, the malondialdehyde (MDA) level, glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) activities in the liver tissue were detected. The small molecular metabolites in the blood of rats were determined by the metabolomics method of ultra-high-performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-MS/MS) combined with multivariate analysis. The enrichment analysis and pathway analysis of the different metabolites were carried out. The therapeutic mechanism of SCP in NAFLD rats was verified by western blot. The results showed that the levels of AST, ALT, TG, TC, and LDL-C in the serum of rats in the SCP group were significantly lower, and the levels of HDL-C were significantly higher than those in the MOD group. The screening and analysis of the metabolic pathways showed that SCP could alleviate the development of NAFLD by regulating the expression of UDP-glucose pyrophosphorylase (UGP2), UDP-glucose 6-dehydrogenase (UGDH), acetyl CoA carboxylase (ACC), and fatty acid synthase (FAS) in the liver of NAFLD rats. This study may provide a theoretical basis for the development and utilization of SCP.
RÉSUMÉ
The aim of this study was to analyze the active components of Schisandra chinensis on liver injury and its mechanism in mice by network pharmacology. The active components of S. chinensis were found through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and their corresponding targets were predicted. The targets of liver injury were searched through Therapeutic Targets Database (TTD), DisGeNET and drugbank databases, and the Venn diagram was constructed to obtain the action targets. The "drug-active component-target" network and protein-protein interaction network (PPI) were constructed by using STRING database and Cytoscape software, and the key targets were further screened by the enrichment analysis of relevant KEGG pathways. Finally, a CCl4-induced mouse liver injury model was established to verify the efficacy and related targets of S. chinensis and clarify its mechanism. Eight active components and 56 related targets of S. chinensis were screened out based on their oral bioavailability (OB) and drug likeness (DL). Five targets of S. chinensis related to liver injury were found by using the Venn diagram. The key targets, namely Ptgs2 and Nos2 genes, were further screened out by constructing a PPI network, and Schisandrol B (SCB) was considered the key component most closely related to the liver injury in S. chinensis. The results indicate that SCB may play a role in the treatment of the CCl4-induced liver injury by down-regulating the expression of iNOS and COX-2, and regulating the expression of NF-κB and IL-17 signaling pathway to inhibit the expression of proinflammatory factors.
Sujet(s)
Lésions hépatiques dues aux substances , Médicaments issus de plantes chinoises/pharmacologie , Foie/traumatismes , Pharmacologie des réseaux/méthodes , Agents protecteurs/pharmacologie , Schisandra/composition chimique , Animaux , Tétrachloro-méthane/toxicité , Lésions hépatiques dues aux substances/traitement médicamenteux , Lésions hépatiques dues aux substances/étiologie , Lésions hépatiques dues aux substances/métabolisme , Lésions hépatiques dues aux substances/anatomopathologie , Cyclooxygenase 2/métabolisme , Modèles animaux de maladie humaine , Médicaments issus de plantes chinoises/composition chimique , Médicaments issus de plantes chinoises/usage thérapeutique , Interleukine-17/métabolisme , Foie/effets des médicaments et des substances chimiques , Foie/métabolisme , Foie/anatomopathologie , Mâle , Médecine traditionnelle chinoise , Souris de lignée ICR , Inhibiteur alpha de NF-KappaB/métabolisme , Facteur de transcription NF-kappa B/métabolisme , Nitric oxide synthase type II/métabolisme , Agents protecteurs/composition chimique , Agents protecteurs/usage thérapeutique , Cartes d'interactions protéiques , Transduction du signal/effets des médicaments et des substances chimiques , Facteur-6 associé aux récepteurs de TNF/métabolisme , Facteur de transcription RelA/métabolismeRÉSUMÉ
Free radical accumulation in the body will cause oxidative stress damages including the renal damage. Schisandrae Sphenantherae Fructus (Schisandra), a traditional Chinese herbal medicine, has been used throughout the world. Anwulignan, a monomer extracted from Schisandra, has been shown in our previous studies to possess antioxidant and protective effects on the liver, brain and spleen damages in the aging mice. However, its effect on the renal damage caused by aging is not clear. This study showed that anwulignan could significantly increase the kidney index, the creatinine clearance, the activities of superoxide dismutase, catalase and glutathione peroxidase; reduce the urinary protein concentration, the serum urea nitrogen and creatinine content, the content of malondialdehyde and 8-hydroxylated deoxyguanosine in the renal tissue; and improve the renal tissue damage. Moreover, anwulignan increased the production of Nrf2, HO-1 and NQO1 proteins and decreased the production level of Keap1 protein in the renal tissue in the d-galactose induced aging mice. These results suggest that anwulignan significantly alleviates the renal damage by its antioxidant effect through regulating the production of Nrf2/ARE pathway-related proteins in the renal tissue in the d-galactose induced aging mice. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-021-00951-7.
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Gastric ulcer is one of the most common gastrointestinal diseases. Anwulignan (AN) is a major active component of Schisandra sphenanthera Rehd. This study was designed to evaluate the protective effect of AN against the acute gastric ulcer induced by HCl/ethanol in mice. The mice were given HCl/ethanol by gavage to establish an acute gastric ulcer model. Then, the serum and gastric tissue samples were taken for biochemical analyses. The results showed that the pretreatment with AN could significantly reduce the gastric ulcer index (GUI) and increase the ulcer inhibition rate, indicating that AN can protect against gastric ulcers. AN showed its antioxidant roles by decreasing the content of reactive oxygen species (ROS), malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG) and increasing the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) and anti-inflammatory roles by decreasing the content of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and myeloperoxidase (MPO) and increasing the content of interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-10 (IL-10), prostaglandin E2 (PGE2), and nitric oxide (NO) in both serum and gastric tissue. Furthermore, AN also activated the NRF2/ARE signaling pathway and inhibited the MAPK/NF-κB signaling pathway. AN improves the acute gastric ulcer induced by HCl/ethanol in mice, which may be mainly through its antioxidant capacity and anti-inflammatory effect.
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Schisandra chinensis (S. chinensis) is one of the core drugs used for relieving cough and asthma in traditional Chinese medicine. However, there are few basic studies on the treatment of respiratory diseases with S. chinensis in modern pharmacology, and the material basis and mechanism of its antiasthmatic effect are still unclear. Lignans are the main active components of S. chinensis. The aim of this study was to observe the relaxation effect of S. chinensis lignans (SCL) on the tracheal smooth muscle of rats by in vitro tracheal perfusion experiments, and to explore the mechanism by preincubation with L-type calcium channel blocker verapamil, four potassium channel blockers glibenclamide, tetraethylamine, 4-aminopyridine and barium chloride (BaCl2), ß-adrenoceptor blocker propranolol, nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME), and the cyclooxygenase inhibitor indomethacin, respectively. The results showed that SCL (0.25-1.75 mg/mL) reduced the contraction of isolated tracheal smooth muscle induced by acetylcholine, the preincubation with verapamil and glibenclamide could attenuate the relaxation effect, whereas propranolol, 4-aminopyridine, BaCl2, tetraethylamine, L-NAME, and indomethacin had no such effect. These results suggest that SCL has a significant relaxation effect on the isolated tracheal smooth muscle of rats, and the mechanism may be related to the inhibition of extracellular calcium influx and intracellular calcium release from the sarcoplasmic reticulum, as well as the activation of ATP-sensitive potassium channels. These findings may provide a pharmacological basis for the traditional use of S. chinensis to treat asthma.
Sujet(s)
Lignanes , Schisandra , Animaux , Inhibiteurs des canaux calciques/pharmacologie , Lignanes/pharmacologie , Relâchement musculaire , Muscles lisses , Monoxyde d'azote , Inhibiteurs des canaux potassiques/pharmacologie , RatsRÉSUMÉ
BACKGROUD: Schisandra chinensis, a traditional Chinese medicine for liver protection, can significantly improve liver fibrosis. However, it is still unclear which active components in Schisandra chinensis play an anti-fibrosis role. PURPOSE: The purpose of present study was to observe the anti-fibrosis effect of schisantherin A (SCA) on liver fibrosis and explore its underlying mechanism. METHODS: The liver fibrosis model of mice was constructed by the progressive intraperitoneal injection of thioacetamide (TAA), and SCA (1, 2, and 4 mg/kg) was administered by gavage for 5 weeks. The biochemical indicators and inflammatory cytokines were measured, changes in the pathology of the mice liver were observed by hematoxylin & eosin (H&E) and Masson stainings for studying the anti-fibrosis effect of SCA. A hepatic stellate cell (HSCs) activation model induced by transforming growth factor-ß1 (TGF-ß1) was established, and the effect of SCA on the HSCs proliferation was observed by MTT assay. The expressions of target proteins related to transforming growth factor-ß-activated kinase 1 (TAK1)/mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways were evaluated by western blotting, immunohistochemistry or immunofluorescence analysis, to explore the potential mechanism of SCA. RESULTS: SCA could significantly ameliorate the pathological changes of liver tissue induced by TAA, and reduce the serum transaminase level, the hydroxyproline level and the expression of α-smooth muscle actin (α-SMA) and collagen 1A1 (COL1A1) proteins in the liver tissue. SCA could significantly lower the levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) in the serum and liver tissue, and down-regulate the expression of target proteins related to TAK1/MAPK and NF-κB pathways in the liver tissue. The in vitro studies demonstrated that SCA significantly inhibited the proliferation and activation of HCS-T6 cells induced by TGF-ß1, decreased TNF-α and IL-6 levels, and inhibited the TAK1 activation induced by TGF-ß1 and then the expression of MAPK and NF-κB signaling pathway-related proteins. CONCLUSION: Together, SCA can ameliorate the liver fibrosis induced by TAA and the HSC-T6 cell activation induced by TGF-ß1 in mice, and its mechanism may be to inhibit the HSCs activation and inflammatory response by inhibiting TGF-ß1 mediated TAK1/MAPK and signal pathways.
Sujet(s)
Cyclooctanes/pharmacologie , Dioxoles/pharmacologie , Lignanes/pharmacologie , Cirrhose du foie/traitement médicamenteux , Cirrhose du foie/métabolisme , Facteur de croissance transformant bêta-1/métabolisme , Animaux , Lignée cellulaire , Cytokines/métabolisme , Cellules étoilées du foie/effets des médicaments et des substances chimiques , Cirrhose du foie/anatomopathologie , MAP Kinase Kinase Kinases/métabolisme , Mâle , Souris de lignée ICR , Mitogen-Activated Protein Kinases/métabolisme , Facteur de transcription NF-kappa B/métabolisme , Rats , Transduction du signal/effets des médicaments et des substances chimiques , Thioacétamide/toxicitéRÉSUMÉ
Anwulignan is one of the monomer compounds in the lignans from Schisandra sphenanthera In this study, we observed the effect of anwulignan on intestinal ischemia/reperfusion (II/R) injury in male Sprague-Dawley rats and explored the underlying mechanisms. The results showed that pretreatment with oral anwulignan could significantly increase the mesenteric blood microcirculatory flow velocity; relieve the congestion and pathologic injury of jejunum; enhance the autonomic tension of jejunum smooth muscle and its reactivity to acetylcholine; increase the activities of superoxide dismutase, catalase, glutathione S-transferase, and choline acetyltransferase; increase the contents of acetylcholine and glutathione in the serum or jejunal tissue; decrease the activities of myeloperoxidase, protein kinase C, and nicotinamide adenine dinucleotide phosphate oxidase; reduce the contents of malondialdehyde, 8-hydroxy-2-deoxyguanosine, nicotinamide adenine, reactive oxygen species, tumor necrosis factor-α, interleukin (IL)-6, and IL-1ß; increase the expression levels of muscarinic receptor 3, PI3K, phosphorylation protein kinase B, p-GSK3ß Ser9, Nrf2, p-Nrf2, heme oxygenase (decycling) 1, and b-cell lymphoma 2 in the jejunal tissue; and decrease the expression levels of p-GSK3ß Tyr216, kelch-like ECH-associated protein 1, Bax, and cleaved caspase-3, suggesting that anwulignan can ameliorate II/R-induced jejunal tissue injury in rats and that the mechanism may be related to its activating the PI3K/protein kinase B pathway and then regulating the Nrf2/Anti-oxidative Response Element signaling pathway and the expression of apoptosis-related proteins to play antioxidant and antiapoptotic roles. SIGNIFICANCE STATEMENT: Anwulignan can significantly reduce jejunal tissue injury and the production of inflammatory factors in rats with intestinal ischemia-reperfusion injury, improve the antioxidant capacity, and reduce the apoptosis of jejunal tissue, and it has the effect of significantly improving intestinal ischemia-reperfusion injury in rats, suggesting that anwulignan may be used as a potential drug for the prevention and treatment of intestinal ischemia-reperfusion injury or a resource for the development of health food.
Sujet(s)
Lésion d'ischémie-reperfusion , Animaux , Microcirculation , Rats , Rat Sprague-DawleyRÉSUMÉ
Chronic fatigue is frequently accompanied by decreased learning and memory capabilities. Schizantherin A (SCA) is one of the main active monomer components in Schisandra chinensis lignans. In the present study, a chronic fatigue mouse model was established using the exhausted swimming approach to investigate the effects of SCA on learning and memory and its associated mechanism of action. Learning and memory abilities were tested by step through tests and water maze methods. Levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and malondialdehyde (MDA) in hippocampal tissue were measured by corresponding assays. The effect of SCA on the expression of kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Bcl2, Bax and cleaved caspase-3 were determined by western blot. The present results showed that SCA can improve the learning and memory capabilities of chronic fatigue mice. SCA was found to increase the activities of SOD and CAT in addition to increasing the levels of GSH but reduced the levels of MDA in hippocampus tissues. Furthermore, SCA treatment downregulated the protein expression levels of Keap1, Bax and cleaved caspase-3 and upregulated the protein expression levels of Nrf2, HO1 and Bcl2 in the hippocampus. These results suggested that modulations in the Nrf2-Keap1-antioxidant response element pathway, anti-oxidative and anti-apoptosis effects are the causes underlying the improvements from SCA treatment on the learning and memory abilities of chronic fatigue mice.
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Schisandrin B (Sch B), a lignan compound in Schisandra, possesses antioxidant, anti-inflammatory, and antiobesity activities. The effect of Sch B on melanogenesis and molecular mechanisms are still unknown. Therefore, we aimed to investigate the antimelanogenic effects of Sch B on α-melanocyte-stimulating hormone-induced B16F10 cells and elucidate the underlying molecular mechanisms. We found that Sch B significantly suppressed melanin content and mushroom tyrosinase (TYR) activity. Sch B treatment decreased the expression of TYR, melanocyte-inducing transcription factor (MITF), tyrosinase-related protein (TRP) 1, and TRP2. Moreover, Sch B modulated the phosphorylation of p38, extracellular-regulated protein kinase, c-Jun N-terminal kinase, and cAMP-response element binding protein (CREB), implying that these pathways may be involved in suppressing melanogenesis. Furthermore, we found that Sch B decreased melanogenesis by downregulating MITF and melanogenic enzymes via MAPK and CREB pathways. Overall, these findings indicate that Sch B has the potential use in whitening.
Sujet(s)
Protéine de liaison à l'élément de réponse à l'AMP cyclique/métabolisme , Régulation négative/effets des médicaments et des substances chimiques , Lignanes/pharmacologie , Système de signalisation des MAP kinases/effets des médicaments et des substances chimiques , Mélanines/biosynthèse , Mélanome expérimental/anatomopathologie , Composés polycycliques/pharmacologie , Transduction du signal/effets des médicaments et des substances chimiques , Hormone mélanotrope alpha/antagonistes et inhibiteurs , Animaux , Lignée cellulaire tumorale , Cyclooctanes/pharmacologie , SourisRÉSUMÉ
The molecular mechanism of the regulatory effed of schizandrol A (SA) on the immune function of cyclophosphamide-induced immunosuppressive mice was explored in this study. On the basis of 1619 differentially expressed genes related to the regulatory effect of SA on the immune function of mice screened in our previous study, transcription factors and their corresponding target genes were screened in the Transcriptional Regulatory Element Database (TRED), and a transcription factor target gene regulatory network was constructed. The key nodes of the network were statistically analyzed to clarify the role of transcription factors in the regulatory network. The correlation of network genes with diseases was analyzed with an online annotation tool through the Database for Annotation, Visualization and Integrated Discovery (DAVID). Finally, the key factors related to the regulatory effect of SA on the immune function of mice were screened and verified by animal experiments and the detection of related protein expression by western blot analysis. The results showed that SA could alleviate the immunosuppression induced by cyclophosphamide in mice and regulate the protein expression of Jun, Trp53, and Creb1 in the spleen tissue of mice, together with the transcription factors Atf4 and E2f2. SA may thus play a role in the alleviation of some immunity-related diseases (such as cancer) by regulating the immune function of mice through multiple genes and their transcription factors.
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Superfine sand in waste activated sludge (WAS) increased the uncertainty of anaerobic fermentation. Experiments showed that VFAs production from WAS was positively affected by superfine sand, with an increase from 2513 mg COD/L in the control (without superfine sand) to 3002 mg COD/L with superfine sand. A mechanism study demonstrated that the main factor responsible for the improved VFAs accumulation in response to superfine sand was acetic acid, which increased by nearly 30%. Further investigation exhibited that the process of solubilization and acidification were facilitated by superfine sand and the abundance of anaerobic functional microorganisms was greatly increased. Moreover, the activities of acetate kinase (AK) as well as the quantity of AK encoding gene were greatly promoted by superfine sand. The heat release during WAS anaerobic fermentation with superfine sand was higher than that without superfine sand (25.8 × 10-3 versus 24.7 × 10-3 W·min at about 70 min).
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Sable , Eaux d'égout , Anaérobiose , Acides gras volatils , Fermentation , Concentration en ions d'hydrogèneRÉSUMÉ
Schisandrin B (SchB) is one of the primary active components of Schisandra chinensis (Turcz.) Baill., a traditional Chinese herb that has been used to treat insomnia for hundreds of years. Our previous studies revealed that SchB exerts sedative and hypnotic effects, increasing the content of γ-aminobutyric acid (GABA) and the expression of its receptors in the brain tissues of rats. 5-hydroxytryptamine (5-HT) is another important neurotransmitter involved in sleep regulation, although, to the best of our knowledge, there are no reports of its association with SchB. Therefore, the present study aimed to determine whether the hypnotic effect of SchB was partly due to alterations in the expression of 5-HT. The results indicated that SchB reduced sleep latency and increased sleep duration in parachlorophenylalanine (PCPA)-induced rats with insomnia by increasing 5-HT and 5-hydroxyindoleacetic acid, and upregulating the expression of the 5-HT receptor 1A in the hypothalamus. SchB also increased the ratio of GABA to glutamic acid and the activity of glutamic acid decarboxylase, decreased the activity of GABA transaminase, and upregulated the expression of GABAA receptor α1 and GABAA receptor γ2 in the rat hypothalamus. These results suggested that SchB improved PCPA-induced insomnia in rats, and its effects may be associated with the regulation of GABA and 5-HT levels in the hypothalamus.
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Hyperlipidemia and its associated obesity, hepatic steatosis, and NAFLD are worldwide problems. However, there is no ideal pharmacological treatment for these. Therefore, the complementary therapies that are both natural and safe have been focused. Healthy foods, such as fruit vinegar, may be one of the best choices. In this study, we made a special medicinal fruit vinegar, Schisandra fruit vinegar (SV), and examined its lipid-lowering effects and the underlying mechanisms in a high-fat diet rat model. The results showed that SV significantly reduced the body weight, liver weight, liver index, the serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), free fatty acid (FFA), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA), increased the content of high-density lipoprotein cholesterol (HDL-C) and the activity of superoxide dismutase (SOD), upregulated the expressions of peroxisome proliferative activated receptor (PPAR-α), peroxisomal acyl-coenzyme A oxidase 1 (ACOX1), and carnitine palmitoyltransferase 1 (CPT1) proteins, increased the contents of key component of antioxidant defense NF-E2-related factor 2 (NRF2) and its downstream heme oxygenase-1 (HO-1) protein, and downregulated the expression of Kelch-like ECH-associated protein 1 (KEAP1). These results suggest that SV has weight loss and lipid-lowering effects in HFD rats, which may be related to its upregulation of the expressions of ß-oxidation -elated PPAR-α, CPT1, and ACOX1 and the regulation of the expressions of antioxidant pathway-related KEAP1-NRF2-HO-1. Therefore, all these data provide an experimental basis for the development of SV as a functional beverage which is safe, effective, convenient, and inexpensive.
RÉSUMÉ
Purpose/Aim: Pulmonary fibrosis (PF) is characterized by the progressive and ultimately fatal accumulation of fibroblasts and extracellular matrix in the lung that distorts its architecture and compromises its function.Objective: The present study investigated the potential protective effects of schisandrin B (Sch B) on the Wingless/Integrase-1 (Wnt) signaling pathway in attenuating inflammation and oxidative stress in ICR mice.Methods: Sixty healthy ICR mice were randomly divided into the following groups: control group, bleomycin (BLM) group, Sch B low dose (Sch B-L) group, Sch B medium dose (Sch B-M) group, Sch B high dose (Sch B-H) group, and dexamethasone (DXM) group. The expression of transforming growth factor (TGF)-ß1 was examined by ELISA. In addition, the levels of superoxide dismutase (SOD), hydroxyproline (HYP), and the total antioxidant capacity (T-AOC) were determined. The protein and mRNA levels of matrix metalloproteinase 7 (MMP7) and ß-catenin in mice were analyzed by western blot and quantitative real -quantitative time PCR (qRT-PCR), respectively.Results: Lung tissues from the BLM group exhibited significantly more inflammatory changes and a significantly greater number of collagen fibers than lung tissues from the control group. In addition, the lung tissues from these BLM-treated mice exhibited slightly increased MMP7 and ß-catenin protein expression. Lung tissues from the Sch B-H group exhibited fewer inflammatory changes and fewer collagen fibers than lung tissues from the BLM group. Furthermore, the lung tissues from the Sch B-H mice exhibited decreased HYP and TGF-ß1 levels, but increased SOD and T-AOC levels.Conclusions: The present study provided evidence that Sch B may be a potential therapeutic agent for the treatment of PF.
Sujet(s)
Bléomycine/pharmacologie , Integrases/métabolisme , Lignanes/pharmacologie , Composés polycycliques/pharmacologie , Fibrose pulmonaire/induit chimiquement , Fibrose pulmonaire/traitement médicamenteux , Transduction du signal/effets des médicaments et des substances chimiques , Protéine Wnt1/métabolisme , Animaux , Cyclooctanes/pharmacologie , Hydroxyproline/métabolisme , Inflammation/traitement médicamenteux , Inflammation/métabolisme , Poumon/effets des médicaments et des substances chimiques , Poumon/métabolisme , Mâle , Souris , Souris de lignée ICR , Stress oxydatif/effets des médicaments et des substances chimiques , Fibrose pulmonaire/métabolisme , Superoxide dismutase/métabolisme , Facteur de croissance transformant bêta-1/métabolismeRÉSUMÉ
Polysaccharide from Schisandra chinensis has the effect of lowering blood glucose and improving insulin resistance (IR). However, its underlying mechanism remains unclear. In this study, a rat model of type 2 diabetes (T2D) was created to explore whether S. chinensis acidic polysaccharide (SCAP) would improve the IR in T2D rats by inhibiting inflammation. A combination of a high-fat diet and low dose of streptozotocin (STZ, 30 mg/kg, intraperitoneally) were administered to rats for establishing the T2D model. Then, these T2D rats were orally administered with SCAP (25, 50, or 100 mg/kg) for 8 weeks. The results indicated that SCAP significantly lowered the fasting blood glucose, elevated the fasting insulin, and improved glucose tolerance. SCAP also decreased the serum interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and nuclear factor-κB (NF-κB) levels, as well as their mRNA expression in the liver tissue. Further, SCAP significantly inhibited the upregulation of phosphorylated c-Jun N-terminal kinase (p-JNK) and NF-κB protein, and it increased phosphorylated insulin receptor substrate-1 (p-IRS-1), phosphorylated phosphatidylinositol 3-kinase (p-PI3K), and phosphorylated protein kinase B (p-AKT) protein expression levels significantly. These results suggest that SCAP improves the IR in T2D rats by inhibiting inflammation.
Sujet(s)
Diabète de type 2/thérapie , Inflammation/thérapie , Insulinorésistance , Polyosides/pharmacologie , Schisandra/composition chimique , Animaux , Glycémie/métabolisme , Protéine C-réactive/métabolisme , Diabète expérimental/thérapie , Alimentation riche en graisse , Insuline/sang , Substrats du récepteur à l'insuline/génétique , Substrats du récepteur à l'insuline/métabolisme , Interleukine-1 bêta/sang , Interleukine-6/sang , Foie/effets des médicaments et des substances chimiques , Foie/métabolisme , Mâle , Facteur de transcription NF-kappa B/sang , Phosphatidylinositol 3-kinases/génétique , Phosphatidylinositol 3-kinases/métabolisme , Protéines proto-oncogènes c-akt/génétique , Protéines proto-oncogènes c-akt/métabolisme , Rats , Rat Wistar , Facteur de nécrose tumorale alpha/sangRÉSUMÉ
The aim of this paper was to investigate the active components of Schisandra chinensis in the treatment of asthma and the related mechanisms by a network pharmacology approach. The active components of Schisandra chinensis and the corresponding targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Eight active components in Schisandra chinensis and 56 related targets were screened out according to two indicators, oral bioavailability (OB) and drug-likeness (DL). A total of 132 targets related to asthma were screened out through Therapeutic Target Database (TTD) data. The String database and Cytoscape software were used to build the "drug-active compound-target" network and protein-protein interaction (PPI) network. The key targets were further predicted by the analysis of related biological processes and the pathway-enrichment. A total of 10 intersection targets between Schisandra chinensis and asthma were obtained by building Venn diagrams, and lignans in Schisandra chinensis were found to be associated with asthma. The key targets Ptgs2 and Nos2 were further screened out, and schisandrol B (SCB) was predicted as the most related key component to asthma. A mouse asthma model was established with ovalbumin and aluminum hydroxide for verifying the effect of SCB and related mechanisms. The results showed that SCB could inhibit the gene expression of proinflammatory factors to play a therapeutic role in asthma by reducing the expression of Nos2 and Ptgs2 and regulating the NF-κB signaling pathway to intervene in the process of cell metabolism in mice. These results suggest that SCB can alleviate the severity of asthma through the mechanisms predicted by network pharmacology, and provide a basis for further understanding of the application of Schisandra chinensis in the treatment of asthma.