RESUMO
This article applies nuclear magnetic resonance technology to the study of boron-containing traditional Chinese medicine, in order to explore the morphological evolution of boron elements in traditional Chinese medicine. Borax is a traditional Chinese medicine with anti-corrosion, anti-inflammatory, antibacterial, and anticonvulsant effects. It is made by boiling, removing stones, and drying borax minerals like borate salts. This article introduces an 11B nuclear magnetic resonance method for identifying and characterizing boron-containing compounds in TCM. We applied this technology to borax aqueous solutions in different chemical environments and found that with boron mixed in the form of SP2 hybridization in equilateral triangles and SP3 hybridization in equilateral tetrahedra, the pH changes in alkaline environments significantly affected the ratio of the two. At the same time, it was found that in addition to the raw material peak, boron signals of other boron-containing compounds were also detected in 20 commercially available boron-containing TCM preparations. These new boron-containing compounds may be true pharmaceutical active ingredients, and adding them directly to the formula can improve quality and safety. This article describes the detection of 11B NMR in boron-containing traditional Chinese medicine preparations. It is simple, non-destructive, and can provide chemical fingerprint studies for boron-containing traditional Chinese medicine.
Assuntos
Boratos , Boro , Medicina Tradicional Chinesa , Espectroscopia de Ressonância MagnéticaRESUMO
OBJECTIVE: To investigate the effects of Clean-DM1 (C-DM1), a polyherbal formulation of Radix Scrophulariae, Radix Astragali, Rhizoma Atractylodis, and Radix Salviae Miltiorrhizae, on high-fat diet (HFD)-induced diabetes mice. METHODS: The information about active components of C-DM1 extract and molecular mechanism was obtained from network pharmacology analysis. Main compounds of C-DM1 extract by high performance liquid chromatography-mass spectrometry (HPLC-MS) analysis were conducted for quality control. For in vivo study, mice were induced diabetes by HFD for 12 weeks. The mice in the normal group (Nor) were maintained with a regular diet and treated with saline by gavage. The HFD model mice were randomly divided into 3 groups, including a HFD diabetic model group, a C-DM1 extract-administered group (C-DM1, 500 mg/kg), and metformin-administered groups (Met, 500 mg/kg), 8 mice in each group. Food intake, body weight (BW), and fasting blood glucose (FBG) levels were recorded weekly for 4 weeks. After 4 weeks of treatment, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood glucose, low-density lipoprotein cholesterol (LDL-C) were determined using an automated clinical chemistry analyzer, and homeostatic model for assessing insulin resistance (HOMA-IR) levels and oral glucose tolerance test (OGTT) were detected. The histopathological changes of liver and pancreatic tissues were observed by hematoxylin-eosin staining. Insulin receptor substrate (IRS)/phosphatidylinositol 3 kinase (PI3K)/ protein kinase B (AKT) and adenosine 5'-monophosphate-activated protein kinase (AMPK) expressions in liver and pancreas tissues were detected by Western blot analysis. RESULTS: HPLC-MS identified dihydroisotanshinone, dihydroisotanshinone I, cryptotanshinone, harpagoside, and atractyloside A in C-DM1 extract. The administration of C-DM1 extract significantly decreased body weight, calorie intake, and the levels of blood glucose and insulin in the diabetic mice (P<0.05 or P<0.01). The C-DM1 extract administration improved the impaired glucose tolerance and insulin resistance in the diabetic mice and significantly decreased the levels of LDL-C, ALT and AST (P<0.01). The C-DM1 extract inhibited the histopathological changes of fatty liver and hyperplasia of pancreatic islets in the diabetic mice. The C-DM1 extract significantly increased the phosphorylation of IRS, AKT, and AMPK and the expression of PI3K in pancreas and liver tissues (P<0.05 or P<0.01), which was consistent with the analysis results of network pharmacology. CONCLUSION: C-DM1 extract improved diabetes symptoms in long-term HFD-induced mice by regulation of IRS/PI3K/AKT and AMPK expressions in pancreas and liver tissues, suggesting that C-DM1 formulation may help prevent the progression of T2DM.
Assuntos
Diabetes Mellitus Experimental , Resistência à Insulina , Camundongos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Glicemia/metabolismo , Dieta Hiperlipídica/efeitos adversos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Proteínas Substratos do Receptor de Insulina/metabolismo , LDL-Colesterol , Fígado , Pâncreas/patologia , Peso Corporal , República da CoreiaRESUMO
This study aims to optimize the parameters for stir-frying of Kansui Radix with vinegar based on the conversion of representative toxic diterpenes, which is expected to serve as a reference for the standardized production of Kansui Radix stir-fried with vinegar. To be specific, the toxic components [3-O-(2'E,4'Z-decadienoyl)-20-O-acetylingenol(3-O-EZ), kansuiphorin C(KPC)] in Kansui Radix and the products(ingenol, 20-deoxyingenol) after the stir-frying with vinegar were selected. The toxicity to intestine and water-draining activity were evaluated with NCM460(normal human colon mucosal epithelial cell line) and HT-29(a human colorectal adenocarcinoma cell line). An HPLC method was then developed to assess the conversion of toxic components. On this basis, temperature, time, and amount of vinegar for the processing of Kansui Radix were optimized with the Box-Behnken design and the content of ingenol and 20-deoxyingenol as evaluation index. The results showed that after the stir-frying of Kansui Radix with vinegar, 3-O-EZ and KPC were first converted to monoester 3-O-(2'E,4'Z-decadienoyl)ingenol(3-EZ) and 5-O-benzoyl-20-deoxyingenol(5-O-Ben) and finally to almost non-toxic ingenol and 20-deoxyingenol, respectively. Meanwhile, the water-draining activity was retained. Six compounds had a good linear relationship with the peak area in the corresponding concentration ranges(R~2≥0.999 8), and the average recovery fell in the range of 98.20%-102.3%(RSD≤2.4%). The content of representative diterpenes and intermediate products was 14.78%-24.67% lower in the Kansui Radix stir-fried with vinegar than in the Kansui Radix, while the content of the conversed products was 14.37%-71.37% higher. Among the process parameters, temperature had significant influence on the total content of products, followed by time. The optimal parameters were 210 â, 15 min, and 30% vinegar. The relative error between the experimental results and the predicted values was 1.68%, indicating that the process was stable and reproducible. The strategy of screening optimal parameters for stir-frying of Kansui Radix with vinegar based on the transformation of toxic components can help improve the production stability, reduce the toxicity, and ensure the efficacy of Kansui Radix stir-fried with vinegar, which can serve as a reference for the process optimization of similar toxic Chinese medicinals.
Assuntos
Ácido Acético , Euphorbia , Humanos , Células HT29RESUMO
BACKGROUND: Traditional bismuth-containing quadruple therapy, as a first-line eradication treatment for Helicobacter pylori (H. pylori), has several disadvantages, including drug side effects, low medication adherence, and high costs. Trials of high-dose dual treatment have demonstrated its advantages, which include good safety and adherence profiles. In this study, we investigated the efficacy, safety, and compliance of a high-dose dual therapy when compared with bismuth-based quadruple treatment for the initial eradication of H. pylori infection on Hainan Island, China. METHODS: We randomized 846 H. pylori-infected patients into two groups. A bismuth-containing quadruple therapy group was administered the following: esomeprazole 20 mg, amoxicillin 1000 mg, and clarithromycin 500 mg twice daily, and colloidal bismuth pectin in suspension 150 mg three times/day for 2 weeks. A high-dose dual therapy group was administered the following: esomeprazole 20 mg four times/day and amoxicillin 1000 mg three times/day for 2 weeks. Patients were given a 13C urea breath test at 4 weeks at treatment end. Adverse effects and compliance were evaluated at follow-up visits. RESULTS: Eradication rates in the high-dose dual therapy group were: 90.3% (381/422, 95% confidence interval [CI]: 87.1%-92.9%) in intention-to-treat (ITT) and 93.6% (381/407, 95% CI: 90.8%-95.8%) in per-protocol (PP) analyses. Eradication rates were 87.3% in ITT (370/424, 95% CI: 83.7%-90.3%) and 91.8% in PP analyses (370/403, 95% CI: 88.7%-94.3%) for quadruple therapy, with no statistical differences (P = 0.164 in ITT and P = 0.324 in PP analyses). Adverse effects were 13.5% (55/407) in the dual group and 17.4% (70/403) in the quadruple group (P = 0.129). Compliance was 92.4% (376/407) in the dual group and 86.6% (349/403) in the quadruple group (P = 0.007). CONCLUSIONS: High-dose dual therapy had high eradication rates comparable with bismuth-based quadruple treatment, with no differences in adverse effects, however higher adherence rates were recorded.
Assuntos
Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/etiologia , Bismuto/uso terapêutico , Bismuto/efeitos adversos , Antibacterianos , Esomeprazol , Quimioterapia Combinada , Amoxicilina/efeitos adversos , Resultado do Tratamento , Inibidores da Bomba de Prótons/efeitos adversosRESUMO
α-Glucosidase is one of the main enzymes causing elevated blood glucose, and Coreopsis tinctoria extract can be used as a natural inhibitor of α-Glucosidase. Therefore, a new method was proposed for predicting the inhibitory activity on α-Glucosidase of Coreopsis tinctoria extract based on near infrared spectroscopy. The absorbance of the inhibitory system was measured by ultraviolet spectroscopy, which was used to study the inhibitory activity on a-glucosidase of Coreopsis tinctoria extract. The near infrared spectra of the solid samples were collected. By selecting spectral preprocessing and optimizing spectral bands, a rapid prediction model of the inhibitory activity was established by partial least squares regression. The root mean square error of cross-validation (RMSECV), correlation coefficient (R) value and the ratio of prediction to deviation (RPD) value were used as indicators of the evaluation model. The near infrared spectrum model was established by combining the best spectral preprocessing of the continuous wavelet transform (CWT) and the best spectral band. The root mean square error of cross-validation (RMSECV) of this model was 0.815%, the correlation coefficient (R) value was 0.942, and the ratio of prediction to deviation (RPD) was 3.0. The root mean square error of prediction (RMSEP) of the model by prediction set was 0.819%, the correlation coefficient (R) value was 0.950, and the RPD was 3.2. The model shows that the fitting relationship between the predicted inhibition value and the reference inhibition value of the near infrared spectral model is good. The results showed that there was a good correlation between near infrared spectroscopy and the inhibitory activity of Coreopsis tinctoria extract. Thus, the established model was robust and effective and could be used for rapid quantification of α-Glucosidase inhibitory activity. The prediction method is simple and rapid, and can be extended to study the inhibition of other medicinal plants.
Assuntos
Coreopsis , alfa-Glucosidases , Ecossistema , Análise dos Mínimos Quadrados , Extratos Vegetais , Espectroscopia de Luz Próxima ao InfravermelhoRESUMO
Metastasis is the leading cause of death in breast cancer patients. Osthole, as an active compound detected in the traditional Chinese medicine Wenshen Zhuanggu Formula, has shown a promising anti-metastatic activity in human breast cancer cells, but the underlying mechanisms remain ambiguous. In this study we elucidated the anti-metastatic mechanisms of osthole in highly metastatic breast cancer cells and a zebrafish xenograft model. We showed that the expression of integrin α3 (ITGα3) and integrin ß5 (ITGß5) was upregulated in highly metastatic MDA-MB-231, MDA-MB-231BO breast cancer cell lines but was downregulated in poorly metastatic MCF-7 breast cancer cell line, which might be the key targets of osthole's anti-metastatic action. Furthermore, we showed that knockdown of ITGα3 and ITGß5 attenuated breast cancer cell migration and invasion possibly via suppression of FAK/Src/Rac1 pathway, whereas overexpression of ITGα3 and ITGß5 caused the opposite effects. Consistently, osthole significantly inhibited breast cancer metastasis by downregulating ITGα3/ITGß5 signaling in vitro and in vivo. These results provide new evidence that osthole may be developed as a candidate therapeutic drug for metastatic breast cancer.
Assuntos
Neoplasias da Mama , Animais , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular , Cumarínicos/farmacologia , Cumarínicos/uso terapêutico , Feminino , Humanos , Invasividade Neoplásica/prevenção & controle , Peixe-ZebraRESUMO
Implant-associated infections is a main factor leading to the failure of titanium (Ti) implants. Micro-arc oxidation is a convenient and effective technique to form a biocompatible metal (Ag+, Cu2+ and Zn2+) ions-doped TiO2 coatings to combat bacterial infections. However, compared with the sterilization by metal ions, light-triggered antibacterial therapies have accepted more attention due to its higher antibacterial efficiency and security. Although TiO2 is an excellent photocatalyst, it can be triggered by ultraviolet light due to the wide band gap. Herein, molybdenum disulfide (MoS2) modified TiO2 coating was fabricated on Ti by a hybrid process of micro-arc oxidation and hydrothermal treatment. The hybrid coating exhibits excellent antibacterial activity under the irradiation of 808 nm near-infrared light because of the synergistic antibacterial effects of reactive oxygen species and hyperthermia, and Staphylococcus aureus (S. aureus) biofilm can be eradicated within 15 min both in vivo and in vitro. Furthermore, collagen decorated on the surface of the hybrid coating can improve the proliferation, adhesion and spreading of MC3T3-E1 osteoblasts.
Assuntos
Substitutos Ósseos , Osso e Ossos/fisiologia , Titânio/química , Células 3T3 , Animais , Antibacterianos/farmacologia , Biofilmes , Adesão Celular , Proliferação de Células , Materiais Revestidos Biocompatíveis/farmacologia , Cobre/química , Dissulfetos/química , Técnicas In Vitro , Íons , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Molibdênio/química , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Fotoquímica , Ratos , Espécies Reativas de Oxigênio , Prata/química , Staphylococcus aureus/metabolismo , Propriedades de Superfície , Zinco/químicaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Jinfukang has long been used for the clinical treatment of lung cancer. Previous studies have shown that Jinfukang can induce the apoptosis of circulating tumor cells by intervening ROS-mediated DNA damage pathway. However, whether Jinfukang can inhibit the metastasis of circulating tumor cells and its mechanism are still unclear. AIM OF THE STUDY: To further investigate the mechanism of Jinfukang in anti-metastasis of lung cancer from the perspective of intervention of tumor exosomes. MATERIALS AND METHODS: The invadopodia formation was determined with immunofluorescence. Invasion and migration were detected using the Transwell assay. Ultracentrifugation was used to isolate exosomes. Exosomes were characterized by electron microscopy, nanoparticle tracking analysis and immunoblotting, and the protein profile was evaluated by proteomic analysis. The molecular functions, biological processes and signaling pathway enrichment analysis were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Key differentially expressed proteins were verified by Western blot. RESULTS: Jinfukang can inhibit the expression of MMP14, cortactin, Tks5 and the formation of invadopodia of CTC-TJH-01 cells. Furthermore, Jinfukang can significantly inhibit the invasion and migration of CTC-TJH-01 cells. The diameter of exosomes extracted from the CTC-TJH-01 cells treated by Jinfukang was 30-100 nm, and the exosomal markers CD63, CD81 and TSG101 were expressed. We identified 680 deferentially expressed proteins. Gene oncology analysis indicated that exosomes were mostly derived from plasma membrane and mainly involved in protein localization and intracellular signaling. The ingenuity pathway analysis showed that the EGF pathway was significantly inhibited, whereas the GP6 signaling pathway was significantly activated. We also confirmed that Jinfukang inhibited the expression of EGF pathway-related proteins in CTC-TJH-01 cells. Besides, when EGF was used to activate EGF signaling pathway, the inhibition of Jinfukang on CTC cell metastasis was reversed. CONCLUSION: Jinfukang inhibits the metastasis of CTC-TJH-01 cells through the EGF pathway.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Exossomos/efeitos dos fármacos , Exossomos/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Células Neoplásicas Circulantes/efeitos dos fármacos , Células Neoplásicas Circulantes/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , MicroRNAs/metabolismo , Proteômica/métodos , Transdução de Sinais/efeitos dos fármacosRESUMO
Bioassay-guided fractionation of the methanolic extract from the roots of Cynanchum atratum has resulted in the isolation of three new pregnane glycosides (1-3) along with four known compounds (4-7). Their structures were identified by analysis of the spectroscopic data including extensive 2D NMR. All of the isolates were evaluated for their potential to inhibit the melanin production in α-melanocyte stimulating hormone (α-MSH)-activated B16 melanoma cells. Of these, compounds 4-7 dose-dependently inhibited the melanin production with the IC50 values ranging from 4⯵M to 33⯵M.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Cynanchum/química , Glicosídeos/farmacologia , Melaninas/antagonistas & inibidores , Melanoma Experimental/tratamento farmacológico , Extratos Vegetais/farmacologia , Pregnanos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Glicosídeos/química , Glicosídeos/isolamento & purificação , Humanos , Melaninas/biossíntese , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Conformação Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/química , Pregnanos/química , Pregnanos/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
Wenshen Zhuanggu formula (WSZG) is a traditional Chinese medicine used as an adjuvant for the prevention of bone metastases in breast cancer patients. In this study we investigated the efficacy of WSZG in preventing bone metastases and the potential mechanisms in a mouse xenograft model of breast cancer bone metastases. This model was established by injection of human MDA-MB-231BO-Luc breast cancer cells alone or a mixture of the cancer cells with bone marrow-derived mesenchymal stem cells (BMSCs) into left ventricle of the heart in female nude mice. Then the mice were treated with WSZG (3.25, 6.5 or 13.0 mg·kg-1·d-1, ig) for four weeks, whereas zoledronic acid (100 µg/kg per week, ig) was used as a positive control. The occurrence and development of bone metastases were monitored via bioluminescent imaging, and bone lesions were assessed using micro-CT. Intracardiac injection of the mixture of MDA-MB-231BO-Luc breast cancer cells with BMSCs significantly facilitated the bone metastatic capacity of the breast cancer cells, and aggravated bone lesions in the mouse xenograft model of breast cancer bone metastases. Administration of WSZG dose-dependently inhibited the incidence and intensity of bone metastases and protected against bone lesions by suppressing osteoclast formation and tumor cell infiltration. Furthermore, administration of WSZG caused a marked reduction in the expression of CCL5/CCR5 and IL-17B/IL-17BR in bone metastatic tissues. The results demonstrate that WSZG exerts potential therapeutic effects in a mouse xenograft model of breast cancer bone metastases, which are partially mediated by weakening the interaction between BMSCs and breast cancer cells in the tumor microenvironment.
Assuntos
Antineoplásicos/farmacologia , Neoplasias Ósseas/prevenção & controle , Neoplasias da Mama/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Antineoplásicos/administração & dosagem , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Difosfonatos/farmacologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Imidazóis/farmacologia , Células-Tronco Mesenquimais/citologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Osteoclastos/metabolismo , Extratos Vegetais/administração & dosagem , Microambiente Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Ácido ZoledrônicoRESUMO
Neogrifolin, a natural biologically active substance isolated from the edible bodies of the mushroom Albatrellus confluens, has been shown to possess several pharmacological properties. No studies were investigated against osteosarcoma cancer. Hence, in this study, we investigated the apoptosis-inducing effects and the mechanisms of neogrifolin on human osteosarcoma cells. Our results demonstrated that neogrifolin induced concentration- and time-dependent suppression of proliferation. Further, induction of apoptosis in U2OS and MG63 osteosarcoma cell lines were also observed. Neogrifolin induced the release of cytochrome c accompanied by activation of caspase-9, caspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP). In addition, z-VAD-fmk, a universal inhibitor of caspases, prevented caspase-3 activation and PARP cleavage and inhibited neogrifolin-induced cell growth inhibition. Furthermore, neogrifolin treatment resulted in a reduction of phosphorylated AKT level, FOXO transcription factor, and glycogen synthase kinase 3 (GSK3). Knockdown of GSK3 with siRNA inhibited the apoptotic effects of neogrifolin. On the other hand, neogrifolin treatment also down-regulated the expression of the inhibitor of apoptosis protein (IAP) in both osteosarcoma cells. Collectively, our results suggested that neogrifolin is a potential candidate for osteosarcoma.
Assuntos
Apoptose/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Resorcinóis/farmacologia , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Quinase 3 da Glicogênio Sintase/metabolismo , Humanos , Osteossarcoma/metabolismo , Fosforilação/efeitos dos fármacos , Extratos Vegetais/farmacologiaRESUMO
Ischemic heart disease (IHD) is the leading cause of death worldwide and remains a major life-threatening factor in humans. Apoptosis has been implicated in the pathogenesis of IHD. The Chinese herbal formula Huo Luo Xiao Ling Dan (HLXLD), one of the commonly used Chinese herbal formulas, consists of Salviae miltiorrhizae, Angelica sinensis, Gummi olibanum, and Commiphora myrrha, with a wide spectrum of pharmacological activity. However, the mechanism of action and molecular targets of HLXLD in the treatment of IHD are unclear. This study aimed to computationally predict the molecular interactions between the major active components of HLXLD and key regulators of apoptosis and then examine the effect of HLXLD on coronary artery ligation-induced acute myocardial ischemia in rats. The molecular interactions between the major active components of HLXLD, including ferulic acid, ligustilide, succinic acid, vanillic acid, tanshinone IIA, tanshinone IIB, danshensu, salvianolic acid A, salvianolic acid C, protocatechuic aldehyde, and ß-boswellic acid and human protein molecules including B cell lymphoma-extra large (Bcl-xl), B cell lymphoma 2 antagonist/killer 1 (Bak1), B cell lymphoma 2 (Bcl-2), procaspase 3, and caspase 9 with regard to hydrogen bond formation, charge interaction, and π-π stacking using Discovery Studio(®) program 3.1. The 12 HLXLD components were predicted by ADMET (absorption, distribution, metabolism, excretion and toxicity) Predictor to have favorable pharmacokinetic and low hepatotoxicity profiles. The acute myocardial ischemia was established by surgical ligation of the left anterior descending coronary artery. The rats were divided into a sham operative group, a model group, a positive control group treated with 0.2 mg/kg isosorbide mononitrate, and groups treated with 2.7, 5.4, or 10.8 g/kg HLXLD. The results showed that administration of HLXLD increased mean arterial pressure, left ventricular systolic pressure, heart rate, and maximal rate of rise/descent of left ventricular pressure levels. Administration of HLXLD significantly ameliorated coronary artery ligation-induced tissue damage in the left ventricle, with restored arrangement of myocardial fibers and recovered myoplasm in rats. Furthermore, HLXLD markedly increased the expression level of Bcl-2 but decreased the level of cleaved caspase 3. Taken together, administration of HLXLD attenuated acute myocardial ischemia-induced damage in cardiomyocytes and inhibited apoptotic death of cardiomyocytes, thereby exerting a cardioprotective effect in rats with IHD. These findings suggest that HLXLD may represent a promising herbal formula for the treatment of cardiovascular disease by counteracting apoptotic cell death via multiple active compounds. More studies are warranted to fully elucidate the mechanisms of action, identify the therapeutic targets, and validate the efficacy and safety of HLXLD in the treatment of IHD.
Assuntos
Apoptose/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Isquemia Miocárdica/tratamento farmacológico , Animais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Humanos , Masculino , Modelos Moleculares , Simulação de Acoplamento Molecular , Estrutura Molecular , Ratos , Ratos Sprague-DawleyRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Wenshen Zhuanggu Formula (WSZG), a traditional Chinese medicine (TCM) empirical prescription, has been used to treat the patients with breast cancer bone metastasis as an adjuvant in clinical practice. To explore the anti-metastatic activity and potential mechanisms of WSZG-containing serum (WSZG-CS) on highly bone-metastatic human breast cancer MDA-MB-231BO cells. MATERIALS AND METHODS: MDA-MB-231BO cells were cultured alone or co-cultured with bone marrow-derived mesenchymal stem cells (BMSCs). Invasion assays were carried out in Matrigel-coated Transwell chambers. CC chemokine 5 (CCL5) and interleukin (IL)-17B secretion levels were detected by ELISA. CCR5 and IL-17BR protein expression levels were determined by immunocytochemistry and Western blot analysis. RESULTS: Compared with control serum, WSZG-CS significantly inhibited BMSC induced MDA-MB-231BO breast cancer cell invasion, reduced CCL5 and IL-17B levels in co-culture supernatants, and downregulated CCR5 and IL-17BR protein expression in breast cancer cells co-cultured with BMSCs. CONCLUSIONS: WSZG-CS exerts an anti-metastatic activity against MDA-MB-231BO breast cancer cells, due to its ability to mitigate the interaction between BMSCs and breast cancer cells mediated via the CCL5/CCR5 and IL-17B/IL-17BR signaling pathways.
Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/metabolismo , Extratos Vegetais/farmacologia , Animais , Linhagem Celular , Linhagem Celular Tumoral , Quimiocina CCL5/metabolismo , Técnicas de Cocultura , Cumarínicos/análise , Feminino , Ficusina/análise , Furocumarinas/análise , Humanos , Interleucina-17/metabolismo , Masculino , Medicina Tradicional Chinesa , Células-Tronco Mesenquimais/metabolismo , Extratos Vegetais/química , Ratos Sprague-Dawley , SoroRESUMO
OBJECTIVE: To observe the effects of electroacupuncture (EA) on circadian rhythm of temperature and melatonin (MT) in depression rats model induced by chronic stress, so as to explore the biological mechanism of EA for depression. METHODS: Twenty-four SD rats were randomly divided into a control group, a model group and an EA group, 8 cases in each one. Rats in the control group were treated with normal diet for 21 days without any treatment. In the model and EA group, rat model was established by chronic unpredictable stress combined with solitarily feeding method, and rats in the EA group was treated with EA at "Baihui" (GV 20), "Yintang" (GV 29) 1 h before stress stimulation everyday, 2 Hz in frequency and intensity was favorable with the head of rat slightly shivering. The needles were retained for 20 min, once a day for totally 21 days. After EA treatment, open-field experiment was adopted to observe the behavioral improvement; the rats temperatures were monitored at six time points (2:00, 6:00, 10:00, 14:00, 18:00, 22:00) and orbital blood sampling was collected. The level of serum MT was tested by enzyme linked immunosorbent assay. The circadian rhythm changes of temperature and serum MT in each group were compared. RESULTS: The numbers of horizontal movement and vertical movement in the model group were obviously lower than those in the control group (both P < 0.05), while those in the EA group were significantly improved compared with those in the model group (both P < 0.01). The circadian rhythm of temperature and MT disappeared in the model group, which was improved into normal level after EA treatment. CONCLUSION: The electroacupuncture has regulation effects on circadian rhythm of temperature and melatonin in depression rat model induced by chronic stress.
Assuntos
Ritmo Circadiano , Depressão/terapia , Eletroacupuntura , Melatonina/metabolismo , Animais , Depressão/metabolismo , Depressão/fisiopatologia , Humanos , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
PURPOSE: The aim of this systematic review was to evaluate the efficacy of any biofeedback treatment on sleep bruxism. METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, ISI Web of Science, System for Information on Grey Literature in Europe, Chinese Biomedical Literature Database, and PsycINFO up to October 2012 for randomized controlled trials and controlled clinical trials involving biofeedback treatment for sleep bruxism. Reference lists of relevant studies were hand searched. Quality assessment and data extraction were performed by two reviewers independently. RESULTS: Seven eligible studies involving 240 participants were finally included. Three of them had moderate risk of bias, and four had high risk of bias. In an electromyographic-measured sleep bruxism episode, meta-analysis showed no significant difference between contingent electrical stimulation and blank control (95% confidence interval = -12.33, 3.38, P = 0.26). Moreover, five studies reported electromyographic activity index. Due to the diversity of biofeedback modalities (auditory, electrical, and visual stimulus) and controls (splint, occlusal adjustment, etc.), these data were unable to be pooled, so only qualitative description was provided. CONCLUSIONS: In the current stage, there is no powerful evidence to support the use of biofeedback technology on sleep bruxism treatment. Contingent electrical stimulation which is defined as a kind of biofeedback modality shows no effect on reducing sleep bruxism episode compared with the no-treatment group. Although many studies support the efficacy of biofeedback treatment, more large sample-sized randomized controlled trials which adopt uniform outcome index are necessitated to verify its application.
Assuntos
Neurorretroalimentação , Bruxismo do Sono/terapia , Ensaios Clínicos Controlados como Assunto , Humanos , Resultado do TratamentoRESUMO
With the continued maturation of III-V nanowire research, expectations of material quality should be concomitantly raised. Ideally, III-V nanowires integrated on silicon should be entirely free of extended planar defects such as twins, stacking faults, or polytypism, position-controlled for convenient device processing, and gold-free for compatibility with standard complementary metal-oxide-semiconductor (CMOS) processing tools. Here we demonstrate large area vertical GaAsxSb1-x nanowire arrays grown on silicon (111) by molecular beam epitaxy. The nanowires' complex faceting, pure zinc blende crystal structure, and composition are mapped using characterization techniques both at the nanoscale and in large-area ensembles. We prove unambiguously that these gold-free nanowires are entirely twin-free down to the first bilayer and reveal their three-dimensional composition evolution, paving the way for novel infrared devices integrated directly on the cost-effective Si platform.
RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Xie-xin decoction (XXD) has been used as a classic formula in China for the treatment of gastrointestinal dysfunction such as ulcerative colitis (UC). However, no potential action mechanisms and active compounds had been systematically investigated. AIM OF THE STUDY: To explore the effectiveness and the material basis of XXD in trinitrobenzene sulfonic acid (TNBS)-induced UC rats. MATERIALS AND METHODS: XXD was administered orally for 8 days at a dosage of 2 or 4g/kg/day. Plasma pharmacokinetic properties and colon tissue concentrations of multiple compounds from XXD were detected. Tissue damage scores, production of interleukin (IL)-10 and myeloperoxidase (MPO), expression of tumor necrosis factor-alpha (TNF-α) and nuclear factor-kappa Bp65 (NF-κBp65) in colon tissues were examined. Canonical correlation analysis was performed to evaluate the relationships between pharmacokinetics and efficacy to elucidate significantly active compounds of XXD. RESULTS: XXD promoted the recovery of colitis and inhibited the colonic inflammation damage in UC rats by reducing the level of MPO and the expression of TNF-α and NF-κBp65, and increasing the production of IL-10 in colon tissues. Efficacy of XXD was positively related with AUC of five plasma compounds (baicalin, berberine, wogonoside, wogonin, and rhein) and concentrations of six colon tissue compounds (coptisine, jatrorrhizine, palmatine, berberine, baicalein and emodin), respectively. CONCLUSIONS: The multiple compounds in plasma and colon tissues from XXD might be the main material basis for therapeutic potentials in UC rats.
Assuntos
Colite Ulcerativa/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Interleucina-10/metabolismo , Masculino , Peroxidase/metabolismo , Fitoterapia , Ratos , Ratos Sprague-Dawley , Fator de Transcrição RelA , Resultado do Tratamento , Ácido Trinitrobenzenossulfônico , Fator de Necrose Tumoral alfa/metabolismoRESUMO
AIM: To evaluate immunological protection of nitric oxide (NO) in hepatopulmonary syndrome and probable mechanisms of ischemia-reperfusion (IR) injury in rat liver transplantation. METHODS: Sixty-six healthy male Wistar rats were randomly divided into three groups (11 donor/recipient pairs). In group II, organ preservation solution was lactated Ringer's solution with heparin 10,â 000/µL at 4â °C. In groupsâ Iâ and III, the preservation solution added, respectively, L-arginine or N(G)-L-arginine methyl ester (L-NAME) (1 mmol/L) based on group II, and recipients were injected with L-arginine or L-NAME (50 mg/kg) in the anhepatic phase. Grafted livers in each group were stored for 6 h and implanted into recipients. Five rats were used for observation of postoperative survival in each group. The other six rats in each group were used to obtain tissue samples, and executed at 3 h and 24 h after transplantation. The levels of alanine aminotransferase (ALT), tumor necrosis factor (TNF)-α and NO metabolites (NOx) were detected, and expression of NO synthase, TNF-α and intercellular adhesion molecule 1 (ICAM-1) was examined by triphosphopyridine nucleotide diaphorase histochemical and immunohistochemical staining. RESULTS: By supplementing L-arginine to strengthen the NO pathway, a high survival rate was achieved and hepatic function was improved. One-week survival rate of grafted liver recipients in groupâ Iâ was significantly increased (28.8 ± 36.6 d vs 4 ± 1.7 d, P < 0.01) as compared with groups II and III. Serum levels of ALT in groupâ Iâ were 2-7 times less than those in groups II and III (P < 0.01). The cyclic guanosine monophosphate (cGMP) levels in liver tissue and NOx in groupâ Iâ were 3-4 times higher than those of group II after 3 h and 24 h reperfusion, while in group III, they were significantly reduced as compared with those in group II (P < 0.01). The levels of TNF-α in groupâ Iâ were significantly lower than in group II after 3 h and 24 h reperfusion (P < 0.01), while being significantly higher in group III than group II (P < 0.01). Histopathology revealed more severe tissue damage in graft liver and lung tissues, and a more severe inflammatory response of the recipient after using NO synthase inhibitor, while the pathological damage to grafted liver and the recipient's lung tissues was significantly reduced in groupâ Iâ after 3 h and 24 h reperfusion. A small amount of constitutive NO synthase (cNOS) was expressed in liver endothelial cells after 6 h cold storage, but there was no expression of inducible NO synthase (iNOS). Expression of cNOS was particularly significant in vascular endothelial cells and liver cells at 3 h and 24 h after reperfusion in group II, but expression of iNOS and ICAM-1 was low in groupâ I. There was diffuse strong expression of ICAM-1 and TNF-α in group III at 3 h after reperfusion. CONCLUSION: The NO/cGMP pathway may be critical in successful organ transplantation, especially in treating hepatopulmonary syndrome during cold IR injury in rat orthotopic liver transplantation.
Assuntos
Síndrome Hepatorrenal/prevenção & controle , Transplante de Fígado/efeitos adversos , Fígado/metabolismo , Fígado/cirurgia , Óxido Nítrico/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Alanina Transaminase/sangue , Animais , Arginina/administração & dosagem , Arginina/metabolismo , GMP Cíclico/metabolismo , Modelos Animais de Doenças , Inibidores Enzimáticos/administração & dosagem , Síndrome Hepatorrenal/etiologia , Síndrome Hepatorrenal/imunologia , Síndrome Hepatorrenal/metabolismo , Síndrome Hepatorrenal/patologia , Imuno-Histoquímica , Molécula 1 de Adesão Intercelular/metabolismo , Fígado/efeitos dos fármacos , Fígado/imunologia , Fígado/patologia , Masculino , NG-Nitroarginina Metil Éster/administração & dosagem , Óxido Nítrico/sangue , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Fatores de Tempo , Fator de Necrose Tumoral alfa/sangueRESUMO
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by cortical and spinal motor neuron dysfunction. Routine magnetic resonance imaging (MRI) studies have previously shown hypointense signal in the motor cortex on T(2)-weighted images in some ALS patients, however, the cause of this finding is unknown. To investigate the utility of this MR signal change as a marker of cortical motor neuron degeneration, signal abnormalities on 3T and 7T MR images of the brain were compared, and pathology was obtained in two ALS patients to determine the origin of the motor cortex hypointensity. Nineteen patients with clinically probable or definite ALS by El Escorial criteria and 19 healthy controls underwent 3T MRI. A 7T MRI scan was carried out on five ALS patients who had motor cortex hypointensity on the 3T FLAIR sequence and on three healthy controls. Postmortem 7T MRI of the brain was performed in one ALS patient and histological studies of the brains and spinal cords were obtained post-mortem in two patients. The motor cortex hypointensity on 3T FLAIR images was present in greater frequency in ALS patients. Increased hypointensity correlated with greater severity of upper motor neuron impairment. Analysis of 7T T(2)(*)-weighted gradient echo imaging localized the signal alteration to the deeper layers of the motor cortex in both ALS patients. Pathological studies showed increased iron accumulation in microglial cells in areas corresponding to the location of the signal changes on the 3T and 7T MRI of the motor cortex. These findings indicate that the motor cortex hypointensity on 3T MRI FLAIR images in ALS is due to increased iron accumulation by microglia.
Assuntos
Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/patologia , Córtex Cerebral/patologia , Ferro/metabolismo , Imageamento por Ressonância Magnética , Adulto , Córtex Cerebral/metabolismo , Feminino , Humanos , Corpos de Inclusão/patologia , Masculino , Microglia/metabolismo , Microglia/patologia , Pessoa de Meia-Idade , Córtex Motor/metabolismo , Córtex Motor/patologia , Neurônios Motores/metabolismo , Neurônios Motores/patologia , Neuroimagem , Medula Espinal/patologiaRESUMO
A non-glycosidic iridoid, campsinol (1), and two iridoid glucosides, 7-O-(Z)-p-coumaroylcachineside V (2) and 7-O-(E)-p-coumaroylcachineside I (3), were isolated from the fresh flowers of Campsis grandiflora along with five known iridoid glycosides, ixoroside (4), campsiside (5), cachineside I (6), 5-hydroxycampenoside (7), and 5-hydroxycampsiside (8), and two known phenylpropanoid glycosides, acteoside (9) and leucosceptoside A (10). The structures of these compounds were determined based on the NMR and Mass spectroscopic data and other chemical evidences.