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Wound healing is a highly orchestrated process involving a variety of cells, including immune cells. Developing immunomodulatory biomaterials for regenerative engineering applications, such as bone regeneration, is an appealing strategy. Herein, inspired by the immunomodulatory effects of gastrodin (a bioactive component in traditional Chinese herbal medicine), a series of new immunomodulatory gastrodin-comprising biodegradable polyurethane (gastrodin-PU) and nano-hydroxyapatite (n-HA) (gastrodin-PU/n-HA) composites were developed. RAW 264.7 macrophages, rat bone marrow mesenchymal stem cells (rBMSCs), and human umbilical vein endothelial cells (HUVECs) were cultured with gastrodin-PU/n-HA containing different concentrations of gastrodin (0.5%, 1%, and 2%) to decipher their immunomodulatory effects on osteogenesis and angiogenesis in vitro. Results demonstrated that, compared with PU/n-HA, gastrodin-PU/n-HA induced macrophage polarization toward the M2 phenotype, as evidenced by the higher expression level of pro-regenerative cytokines (CD206, Arg-1) and the lower expression of pro-inflammatory cytokines (iNOS). The expression levels of osteogenesis-related factors (BMP-2 and ALP) in the rBMSCs and angiogenesis-related factors (VEGF and BFGF) in the HUVECs were significantly up-regulated in gastrodin-PU/n-HA/macrophage-conditioned medium. The immunomodulatory effects of gastrodin-PU/n-HA to reprogram macrophages from a pro-inflammatory (M1) phenotype to an anti-inflammatory and pro-healing (M2) phenotype were validated in a rat subcutaneous implantation model. And the 2% gastrodin-PU/n-HA significantly decreased fibrous capsule formation and enhanced angiogenesis. Additionally, 2% gastrodin-PU/n-HA scaffolds implanted in the rat femoral condyle defect model showed accelerated osteogenesis and angiogenesis. Thus, the novel gastrodin-PU/n-HA scaffold may represent a new and promising immunomodulatory biomaterial for bone repair and regeneration.
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The aim of this experiment was to investigate the effect of soy lecithin on serum-related indicators and liver health in laying hens under the influence of high-fat diets. 180 peak laying hens at 40 weeks of age were randomly assigned to one of the four diets using a 2 × 2 factorial and fed for 5 weeks. The results showed that compared to the low-fat group, the high-fat group had lower egg production (p < 0.05) and higher average daily feed intake and feed-to-egg ratio (p < 0.05). At the 21st day, the serum levels of triglyceride (TC) and superoxide dismutase (SOD) were higher (p < 0.05), high-density lipoproteins cholesterol (HDL-C) levels were lower (p < 0.01), catalase (CAT) activity was lower (p < 0.05), TC and malondialdehyde (MDA) levels in liver were higher (p < 0.01) and SOD activity in liver was lower (p < 0.05) in layers supplemented with soy lecithin. CAT activity in serum was increased (p < 0.01) and total antioxidant capacity (T-AOC) activity in the liver was decreased (p < 0.05) after increasing the dietary fat concentration. The addition of soy lecithin and the increase in dietary fat concentration had a highly significant interaction on serum CAT activity and liver TC content in layers (p < 0.01). At the 35th day, the serum alanine aminotransferase (ALT) activity was higher (p < 0.01), serum glutathione peroxidase (GSH-Px) and CAT activity were higher (p < 0.05), and serum triglyceride (TG) content and total T-AOC capacity activity were lower (p < 0.05) in layers supplemented with soy lecithin. Increasing dietary fat concentration decreased alanine aminotransferase (ALT), aspartate aminotransferase (AST) and GSH-Px activity in serum (p < 0.05). However, it increased TG and MDA content in liver (p < 0.05), and highly decreased SOD content in liver (p < 0.01) in layers. The addition of soy lecithin and increasing dietary fat concentration had a highly significant reciprocal effect on serum ALT viability and CAT viability (p < 0.01) and liver TG and MDA content and SOD viability (p < 0.05) in layers. In conclusion, feeding high-fat diets will adversely affect the laying performance of laying hens, while long-term addition of lecithin can improve the blood lipids and liver lipids of laying hens, enhance the antioxidant capacity of the liver, and maintain liver health.
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The dramatic increase in obesity is putting people under increasing pressure. Lipase inhibitors, as a kind of effective anti-obesity drug, have attracted more and more researchers' attention in recent years because of their advantages of acting on the intestinal tract and having no side effects on the central nervous system. In this study, lipase inhibitor Fu Brick Theophylline (FBT) was screened based on enzyme molecular dynamics, and the inhibition mechanism of lipase inhibitors on obesity was analyzed and discussed at the cellular level and animal model level. We found that FBT had high inhibition effects of lipase with an IC50 of 1.02~0.03 µg/mL. Firstly, the laboratory used 3T3-L1 proadipocytes as models, flow cytometry was used to detect the effects of FBT on the cycle, apoptosis and intracellular ROS activity of proadipocytes. To study the contents of triglyceride, total cholesterol, related metabolites and related gene and protein expression in adipocytes. The results showed that FBT could reduce ROS production and inflammatory factor mRNA expression during cell differentiation. Secondly, by establishing the animal model of high-fat feed ob nutritional obese mice, the morphological observation and gene expression analysis of body weight, fat rate, adipocyte and hepatocyte metabolism of FBT obese mice were further discussed. It was proven that FBT can effectively reduce the degree of fatty liver, prevent liver fibrosis and fat accumulation, and improve the damage of mitochondrial membrane structure. This study provides a theoretical basis for the screening and clinical treatment of lipase inhibitors.
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Lipasa , Teofilina , Células 3T3-L1 , Tejido Adiposo/metabolismo , Animales , Dieta Alta en Grasa/efectos adversos , Humanos , Ratones , Ratones Obesos , Obesidad/tratamiento farmacológico , Obesidad/etiología , Obesidad/metabolismo , Especies Reactivas de Oxígeno , Té/químicaRESUMEN
In this study, the conditions of extraction of loquat flowers polyphenolics were optimized through response surface methodology (RSM). Proper extraction conditions were: solid to liquid ratio 1 g per 50 mL and ethanol concentration 50% at 61°C for 9 min. Furthermore, the antioxidant and anti-polyphenol oxidase (PPO) activity of purified total polyphenolics (PTP) were investigated. PTP displayed strong antioxidant activity with IC50 values of 126.3 ± 8.9, 162.4 ± 6.3 and 94.97 mg ascorbic acid equivalent/g dry weight (mg AAE/d.w.) for ABTS, DPPH, and FRAP assays. In addition, PTP has a substantial inhibitory activity on PPO (IC50 = 115 ± 9.2 µg/mL). From the kinetics analysis, it was proved to be a reversible and mixed-type inhibitor of PPO with KI and KIS values of 76.77 µg/mL and 227.86 µg/mL, respectively. Further, the molecular mechanism underlying the inhibition of PPO by PTP was investigated by molecular docking techniques. The results showed that PTP units could form interaction with the catalytic pocket of PPO through the interaction with amino acid residues in the enzyme active center. The antioxidant activities of PTP together with its effect on PPO activity provide a strong starting point for their practical usage in the food industry.
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Antioxidantes/química , Catecol Oxidasa/antagonistas & inhibidores , Eriobotrya/química , Flores/química , Extractos Vegetales/química , Etanol/química , Cinética , Oxidación-Reducción/efectos de los fármacos , Extractos Vegetales/farmacologíaRESUMEN
This study aimed to investigate the mechanisms of Yu-Ping-Feng-San (YPFS) on attenuating allergic inflammation in the initial stage of atopic dermatitis (AD). AD mouse model was established with fluorescein isothiocyanate (FITC) sensitization and elicitation. Epithelial barrier structure was observed with transmission electron microscope. The populations of dendritic cells (DCs) and group 2 innate lymphoid cells (ILC2s) were detected by flow cytometry. Human immortalized keratinocyte (HaCaT) cells were stimulated with Poly(I:C)/TNF-α in vitro to assessthymic stromal lymphopoietin (TSLP), interleukin (IL)-33 and nuclear factor-κB (NF-κB) levels or expressions by immunofluorescence, enzyme linked immunosorbent assay (ELISA) and western blot. In the initial stage of AD, ear swelling and infiltration of inflammatory cells in ear tissues were markedly attenuated with YPFS treatments. The damaged structures of ear epithelium and the increased levels of Th2-cytokines induced by FITC were significantly rescued in YPFS-treated mice. The production of pro-allergic cytokines, TSLP and IL-33, as well as the cell populations of their target cells DCs and ILC2s were decreased in AD model, respectively. Likewise, the levels of TSLP and IL-33 in Poly(I:C)/TNF-α-stimulated HaCaT cells showed the same results. Lower levels of p-NF-κB were detected with YPFS treatment, and the expressions of TSLP and IL-33 could be further decreased with inhibiting of NF-κB. Therefore, YPFS attenuates allergic inflammation in the initial stage of AD probably through regulating NF-κB-TSLP/IL-33 pathway, which may provide a novel effective target for the prevention and treatment of allergic diseases.
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Antialérgicos/uso terapéutico , Citocinas/metabolismo , Dermatitis Atópica/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Inflamación/prevención & control , Animales , Antialérgicos/farmacología , Línea Celular , Células Dendríticas/patología , Dermatitis Atópica/inducido químicamente , Dermatitis Atópica/metabolismo , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Células Epiteliales/metabolismo , Fluoresceína-5-Isotiocianato/toxicidad , Inflamación/metabolismo , Inflamación/patología , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Linfocitos/metabolismo , Linfocitos/patología , Ratones Endogámicos BALB C , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéuticoRESUMEN
The Janus kinase (JAK) family of tyrosine kinases has been proven to provide targeted immune modulation. Orally available JAK inhibitors have been used for the treatment of immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA). Here, we report the design, synthesis and biological evaluation of 4-(4,5,6,7-tetrahydrofuro[3,2-c]pyridin-2-yl) pyrimidin-2-amino derivatives as JAK inhibitors. Systematic structure-activity relationship studies led to the discovery of compound 7j, which strongly inhibited the four isoforms of JAK kinases. Molecular modeling rationalized the importance of cyanoacetyl and phenylmorpholine moieties. The in vivo investigation indicated that compound 7j possessed favorable pharmacokinetic properties and displayed slightly better anti-inflammatory efficacy than tofacitinib at the same dosage. Accordingly, compound 7j was advanced into preclinical development.
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Aminas/química , Antiinflamatorios/química , Inhibidores de las Cinasas Janus/química , Quinasas Janus/antagonistas & inhibidores , Administración Oral , Aminas/metabolismo , Animales , Antiinflamatorios/metabolismo , Antiinflamatorios/farmacocinética , Antiinflamatorios/uso terapéutico , Artritis/tratamiento farmacológico , Artritis/patología , Sitios de Unión , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Semivida , Humanos , Inhibidores de las Cinasas Janus/metabolismo , Inhibidores de las Cinasas Janus/farmacocinética , Inhibidores de las Cinasas Janus/uso terapéutico , Quinasas Janus/metabolismo , Simulación del Acoplamiento Molecular , Isoformas de Proteínas/antagonistas & inhibidores , Isoformas de Proteínas/metabolismo , Pirimidinas/química , Ratas , Relación Estructura-ActividadRESUMEN
PURPOSE: This study aimed to determine whether resveratrol treatment alleviates endoplasmic reticulum stress and changes the expression of adipokines in adipose tissues and cells. METHODS: 8-week-old male C57BL/6 mice were fed a high-calorie diet (HCD group) or high-calorie diet supplemented with resveratrol (high-calorie diet + resveratrol group) for 3 months. Insulin resistance, serum lipids and proinflammatory indices, the size and inflammatory cell infiltration in subcutaneous and visceral adipose tissues were analyzed. The gene expressions of endoplasmic reticulum stress, adipokines, and inflammatory cytokines were determined. The induced mature 3T3-L1 cells were pretreated with resveratrol and then palmitic acid, and the gene expressions of endoplasmic reticulum stress, adipokines, and inflammatory cytokines were determined. RESULTS: Subcutaneous and visceral adipose tissues in the high-calorie diet-fed mice exhibited adipocyte hypertrophy, inflammatory activation, and endoplasmic reticulum stress. Resveratrol alleviated high-calorie diet-induced insulin resistance and endoplasmic reticulum stress, increased expression of SIRT1, and reversed expression of adipokines in varying degrees in both subcutaneous and visceral adipose tissues. The effects of resveratrol on palmitic acid-treated adipocytes were similar to those shown in the tissues. CONCLUSIONS: Resveratrol treatment obviously reversed adipocyte hypertrophy and insulin resistance by attenuating endoplasmic reticulum stress and inflammation, thus increasing the expression of SIRT1 and inverting the expression of adipokines in vivo and in vitro.
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Adipocitos/efectos de los fármacos , Adipoquinas/metabolismo , Tejido Adiposo/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Ácido Palmítico/farmacología , Estilbenos/farmacología , Células 3T3-L1 , Adipocitos/metabolismo , Tejido Adiposo/metabolismo , Animales , Diferenciación Celular/efectos de los fármacos , Resistencia a la Insulina/fisiología , Lípidos/sangre , Masculino , Ratones , ResveratrolRESUMEN
In this article, medication characteristics of professor Li Dian-gui in treating chronic atrophic gastritis with intestinal metaplasia(CAGIM) were analyzed through traditional Chinese medicine inheritance support system(version 2.5). 276 cases and 625 prescriptions were collected to analyze five types of traditional Chinese medicine(TCM) syndromes and the medicine-syndrome correlation. The results showed that medication characteristics of professor Li Dian-gui in treating CAGIM included drug combination of aromatic medicine bitter-cold herbs, preferring to activating to invigorate the spleen and good at using the qi-regulating drugs. It demonstrated that we can adopt the therapy of Huazhuo Jiedu and Xingpi Xingqi therapies in treating CAGIM in addition to the traditional approach of nourishing Yin and activating blood circulation, opening up a novel approach for TCM in healing the pathema.
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BACKGROUND: Jellyfish envenomation is common along the coastal area, and can cause severe consequences. Naval personnel are among the high-risk population for this injury. The aim of this study was to assess knowledge regarding jellyfish envenomation among naval personnel in a navy unit in northeast China. METHODS: A predesigned questionnaire was distributed to 120 naval members in January 2015. The data of 108 respondents were included in the statistical analysis. RESULTS: We found that 38.0% of the respondents selected jellyfish sting as the common wound in their units, and 13.0% had experienced or observed this injury. In addition, 63.0% of the participants rated their own knowledge as "low" or "none". The average score they got was 5.77 ± 2.50, with only 16.7% getting a score above 60% of the full score. The correct rates of five questions were below 60%. No statistical differences existed in the knowledge score among different groups of respondents defined by socio-demographic variables. CONCLUSIONS: Jellyfish sting is common in this navy unit, but personnel got a low score on the knowledge assessment. They also lacked confidence in first aid. Medical education and training should be implemented to address this issue.
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Mordeduras y Picaduras , Conocimientos, Actitudes y Práctica en Salud , Escifozoos , Adulto , Animales , China , Humanos , Masculino , Personal Militar , Encuestas y Cuestionarios , Adulto JovenRESUMEN
<p><b>OBJECTIVE</b>To observe the effects of electroacupuncture (EA) of different intensities on lactate dehydrogernase (LDH), succinate dehydrogenase (SDH) and ATPase in brain tissue of rats with cerebral ischemia-reperfusion injury (CI/R).</p><p><b>METHODS</b>Forty male SD rats were uniformly randomized into sham operation group (group A), CI/R group (group B), CI/R+5 mA EA (group C), CI/R+3 mA EA (group D) and CI/R+1 mA EA (group E) groups with eight rats in each group. Transient general brain ischemia was induced by four-vessel occlusion and reperfusion. The rats in group C, group D and group E were punctured and stimulated at Baihui (GV20), Mingmen (GV4) and Zusanli (ST36) with the same intermittent and rarefaction-dense wave (30 to 50 Hz) and different electric current intensities: 5 mA, 3 mA and 1 mA for 20 min after CI/R. Then the activities of Na(+)-K(+)-ATPase, SDH and LDH in mitochondria of brain tissue were measured by spectrophotometry. The ischemic cerebral cortex tissue was taken for observing the ultrastructure changes of impaired nerve cells.</p><p><b>RESULTS</b>Compared with group A, the activities of LDH, SDH and Na(+)-K(+)-ATPase were lowerer in the group B (P<0.05 or P<0.01). However, the activities of LDH, SDH and Na(+)-K(+)-ATPase were higher in the group D than those in the group B (P<0.05 orP<0.01). In group A, the anatomical structure of the cerebral cortex cells was basically normal; in group B, the neuronal cellular structures were severely damaged, the neuronal mitochondria got swelling, the mitochondrial cristae were broken, the medullated nerve fifibers were not integrated. In group C, group D and group E, the ultrastructure of impaired neuron were improved. Group D was the best among three groups above.</p><p><b>CONCLUSION</b>EA of 3 mA intensity could strengthen aerobic metabolism by elevating the activities of SDH and LDH, meanwhile maintaining the ionic equilibrium in the exterior and interior brain cell and relieving the cellular edema by reinforcing the activities of Na(+)-K(+)-ATPase.</p>
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Animales , Masculino , Ratas , Encéfalo , Metabolismo , Electroacupuntura , Metabolismo Energético , Mitocondrias , Metabolismo , Ratas Sprague-Dawley , Daño por Reperfusión , MetabolismoRESUMEN
AIM: To observe thickness and morphological changes of bulbar conjunctiva pre- and post epidemic hemorrhagic conjunctivitis ( EHC ) therapy by optical coherence tomography ( OCT) . METHODS: Observed morphological changes and measured the bulbar conjunctiva thicknesses of 29 cases (36 eyes) of incipient (1-2d) EHC patients, who were received and treated by department of ophthalmology, the Putuo Affiliated Hospital of Shanghai University of Traditional Chinese Medicine from May 2013 to December 2013, by OCT. Then measured the thickness again on 7, 14d after the therapy. RESULTS: Among 29 patients (36 eyes), 7d after the EHC therapy, in 27 cured eyes, the full-thickness ( before 344. 00±59. 91μm, after 230. 19±22. 16μm, t=11. 75, PCONCLUSION: The OCT is able to measure the thickness of bulbar conjunctiva in EHC patients. An significant increase was found in full, epithelial and stromal thickness of EHC patients' bulbar conjunctiva. With recovery from the disease, subepithelial fluid, interlaminar fluid and edema of the bulbar conjunctival stroma faded away firstly, which provide references for clinical therapies of the EHC.
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OBJECTIVE: To investigate the effect and mechanism of baicalin against beta-lactamases Escherichia coli (ESBLs E. coli) mediated by toll-like receptor 4 (TLR4) signal transduction pathway. METHOD: The RAW264. 7 cells monolayer pretreated with different concentration of baicalin were inoculated with ESBLs E. coli. The expression of TLR4 mRNA and protein were analyzed by semi-quantitative RT-PCR and Immunofluorescence, respectively. The activity of NF-kappaB was detected by Western blot using total cellular protein. The production of TNF-alpha in supernatant was determined by enzyme linked immunosorbnent assay (ELISA). RESULT: ESBLs E. coli significantly up-regulated the expression levels of TLR4 mRNA and protein in a time-dependent manner, induced the activation of NF-KB in RAW264. 7, enhanced the production of TNF-alpha in supernatant. Baicalin down-regulated the expression of TLR4 mRNA and protein, decreased the activation of NF-KB in RAW264. 7 cells and reduced the production of TNF-alpha in supernatant in a dose-dependent manner. CONCLUSION: Baicailin could inhibit TLR4 signal transduction pathway. The mechanism of baicalin against ESBLs E. coli may be through inhibiting the expression of TLR4 and its signal transduction pathway.
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Infecciones por Escherichia coli/microbiología , Escherichia coli/fisiología , Flavonoides/farmacología , Receptor Toll-Like 4/genética , Animales , Línea Celular , Escherichia coli/efectos de los fármacos , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/genética , Infecciones por Escherichia coli/inmunología , Expresión Génica/efectos de los fármacos , Humanos , Ratones , Receptor Toll-Like 4/inmunologíaRESUMEN
OBJECTIVE: To observe the effect of Yupingfeng San (YPFS) against OVA-induced allergic asthma in mice. METHOD: Mice were injected with OVA to establish the allergic asthma model. They were abdominally injected with 20 microg OVA on day 0 and 14, and inhaled aerosol 0.5% OVA solution for 20 min for seven days. The blank control group was administrated with equal volume of saline. YPFS groups with different doses were administrated intragastrically with YPFS every day, with the crude drug dosage of 3.25, 6.5, 13 g x kg(-1), respectively. The model group and control group were administrated with equal volume of saline. The positive control group was given intraperitoneally injected with 1 mg x kg(-1) DEX since aerosol inhalation. Blood was drawn after the last OVA aerosol inhalation to count the number of Eosnophils (Eos) in blood and detect IgE in serum; BALF was collected to count the number of cells and classify; right lung tissues were evenly grinded to detect cytokines IL-4 and IFN-gamma, and left upper lung lobes were collected for pathologic histology. RESULT: The level of Eos and IgE in serum increased significantly in the model group, and a large number of Eos were detected in BALF. Histopathological changes in lung showed bronchial serous exudation, tubular epithelial cells exfoliation, tube narrowing, widened alveolar septum, and bronchial periarterial lymphocytes infiltration. Homogenate of lung tissues showed increase of IL-4, and decrease in IFN-gamma/IL-4 ratio. YPFS groups with different doses displayed decrease of Eos in blood and BALF and IgE content in serum, and relief of pathologic changes in above models. Meanwhile, IL-4 content in homogenate of lung tissues decreased, with the increase in IFN-gamma/IL-4 ratio. CONCLUSION: YPFS shows the inhibitory effects on OVA-induced allergic asthma, involving down regulation of Eos and IgE levels in blood of asthma mice, and infiltration of inflammatory cells in lung tissues. Meanwhile, it can reduce IL-4 in lung homogenates, increase IFN-gamma/IL-4, and inhibits Th2 polarization.
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Asma/tratamiento farmacológico , Medicamentos Herbarios Chinos/administración & dosificación , Animales , Asma/inducido químicamente , Asma/inmunología , Modelos Animales de Enfermedad , Eosinófilos/efectos de los fármacos , Eosinófilos/inmunología , Humanos , Interferón gamma/inmunología , Interleucina-4/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/efectos adversosRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Qing Ye Dan is a well-known herbal drug that is widely used to treat viral hepatitis in the Yi and Hani minority regions in the Yunnan province of China. MATERIALS AND METHODS: An LC-MS/MS method was developed to determine the levels of swertiamarin in rat plasma. Swertiamarin and naringin (internal standard, IS) were extracted from rat plasma using solid-phase extraction (SPE) to purify the samples. The pharmacokinetics of the following different administration methods of swertiamarin in rats were studied: oral administration of swertiamarin alone, a Qing Ye Dan tablet (QYDT) and co-administration of swertiamarin and oleanolic acid, with each method delivering approximately 20mg/kg of swertiamarin. Non-compartmental pharmacokinetic profiles were constructed by using the software DAS (version 2.1.1), and the pharmacokinetic parameters were compared using an unpaired Student's t-test. RESULTS: The results showed that the pharmacokinetic parameters Cmax, AUC0-∞, Vz/F and CLz/F were significantly different (P<0.05) among the three types of swertiamarin administration. CONCLUSIONS: The data indicate that oleanolic acid and the other ingredients present in QYDT could affect the pharmacokinetic behaviour of swertiamarin in rats.
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Medicamentos Herbarios Chinos/farmacocinética , Etnofarmacología , Glucósidos Iridoides/farmacocinética , Ácido Oleanólico/farmacología , Pironas/farmacocinética , Administración Oral , Animales , China , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/aislamiento & purificación , Interacciones de Hierba-Droga , Glucósidos Iridoides/administración & dosificación , Glucósidos Iridoides/sangre , Glucósidos Iridoides/aislamiento & purificación , Estructura Molecular , Ácido Oleanólico/administración & dosificación , Pironas/administración & dosificación , Pironas/sangre , Pironas/aislamiento & purificación , Ratas , Ratas Sprague-Dawley , Reproducibilidad de los Resultados , Extracción en Fase Sólida , Espectrometría de Masa por Ionización de Electrospray , Swertia/química , ComprimidosRESUMEN
The phenolic glucoside gastrodin, a main constituent of a Chinese traditional herbal medicine, has been known to display several biological and pharmacological properties. However, the role and precise molecular mechanisms explaining how gastrodin suppresses the inflammatory response in septic cardiac dysfunction are unknown. To study this, rat H9c2 cardiomyocytes were treated with gastrodin and/or lipopolysaccharide (LPS). Our results showed that gastrodin treatment strongly suppressed nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) family activation and upregulation of the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in LPS-stimulated H9c2 cardiomyocytes. Simultaneously, gastrodin obviously upregulated the phosphatidylinositol 3-kinase (PI3-K)/Akt signaling in a dose-dependent manner. However, wortmannin, a specific PI3-K inhibitor, blocked the inhibitory effects of gastrodin on LPS-stimulated H9c2 cardiomyocytes. Furthermore, PI3-K/Akt inhibition partially abolished the inhibitory effects of gastrodin on the phosphorylation of inhibitor κB-α (IκB-α), extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK), and activity of NF-κB. Here we report activation of the PI3-K/Akt signaling by gastrodin and that inhibition of this pathway reverses the inhibitory effects of gastrodin on NF-κB and MAPKs activation in H9c2 cardiomyocytes.
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Antiinflamatorios/farmacología , Alcoholes Bencílicos/farmacología , Glucósidos/farmacología , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Miocitos Cardíacos/efectos de los fármacos , FN-kappa B/antagonistas & inhibidores , Fosfatidilinositol 3-Quinasas/fisiología , Transducción de Señal/efectos de los fármacos , Androstadienos/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Activación Enzimática , Interleucina-6/biosíntesis , Lipopolisacáridos/farmacología , Miocitos Cardíacos/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Fosforilación , Ratas , Factor de Necrosis Tumoral alfa/biosíntesis , WortmaninaRESUMEN
<p><b>OBJECTIVE</b>To explore the possible angiogenesis mechanism of Huazhuo Jiedu Hewei Recipe (HJHR) in preventing and treating precancerous lesions of gastric cancer (PLGC).</p><p><b>METHODS</b>Totally 66 Wistar rats were randomly divided into 6 groups, i.e., the normal control group, the model group, the retinoic acid (RA) group, the high dose HJHR group, the middle dose HJHR group, the low dose HJHR group, 11 in each group. PLGC model was duplicated by inserting a spring with Helicobacter. Corresponding medicines were administered to rats in each medicated group once daily by gastrogavage, 2 mL each time for 12 successive weeks. The effect of HJHR on hypoxia induced factor (HIF-1alpha) and vascular endothelial growth factor (VEGF) of PLGC in chronic atrophic gastritis (CAG) rats' gastric mucosa was observed by immunohistochemical assay and Western blot method.</p><p><b>RESULTS</b>Compared with the normal control group, the expression of VEGF and HIF-1alpha increased in the model group (P < 0.05). Compared with the model group, the expression of VEGF and HIF-1alpha decreased in each medicated group (P < 0.05). Besides, they were lower in the high and middle dose HJHR groups than in the RA group and the low dose HJHR group (P < 0. 05). There was no statistical difference between the low dose HJHR group and the RA group (P > 0.05).</p><p><b>CONCLUSION</b>HJHR could prevent and treat PLGC of CAG rats possibly through decreasing the expression of HIF-1alpha and VEGF in a dose-dependent manner.</p>
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Animales , Masculino , Ratas , Medicamentos Herbarios Chinos , Usos Terapéuticos , Mucosa Gástrica , Metabolismo , Gastritis , Metabolismo , Microbiología , Helicobacter , Subunidad alfa del Factor 1 Inducible por Hipoxia , Metabolismo , Neovascularización Patológica , Lesiones Precancerosas , Quimioterapia , Metabolismo , Ratas Wistar , Neoplasias Gástricas , Quimioterapia , Metabolismo , Factor A de Crecimiento Endotelial Vascular , MetabolismoRESUMEN
Scutellarin is the most important flavone glycoside in the herbal drug Erigeron breviscapus (Vant.) Hand.-Mazz. It is used frequently in the clinic to treat ischemic vascular diseases in China. However, the direct relationship between scutellarin and cytochrome P450 (CYP450) is unclear. The present study investigated the in vitro and in vivo effects of scutellarin on cytochrome P450 1A2 (CYP 1A2) metabolism. According to in vitro experiments, scutellarin (10-250 µM) decreased the formation of 4-acetamidophenol in a concentration-dependent manner, with an IC50 value of 108.20 ± 0.657 µM. Furthermore, scutellarin exhibited a weak mixed-type inhibition against the activity of CYP1A2 in rat liver microsomes, with a K(i) value of 95.2 µM. Whereas in whole animal studies, scutellarin treatment for 7 days (at 5, 15, 30 mg/kg, i.p.) decreased the clearance (CL), and increased the T(1/2) (at 15, 30 mg/kg, i.p.), it did not affect the V(d) of phenacetin. Scutellarin treatment (at 5, 15, 30 mg/kg, i.p.) increased the AUC(0-∞) by 14.3%, 67.3% and 159.2%, respectively. Scutellarin at 30 mg/kg also weakly inhibited CYP1A2 activity, in accordance with our in vitro study. Thus, the results indicate that CYP1A2 is inhibited directly, but weakly, by scutellarin in vivo, and provide useful information on the safe and effective use of scutellarin in clinical practice.
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Apigenina/farmacología , Citocromos/antagonistas & inhibidores , Glucuronatos/farmacología , Hígado/efectos de los fármacos , Animales , Apigenina/administración & dosificación , Área Bajo la Curva , Citocromo P-450 CYP1A2 , Citocromos/metabolismo , Relación Dosis-Respuesta a Droga , Activación Enzimática , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/farmacología , Erigeron/química , Femenino , Glucuronatos/administración & dosificación , Concentración 50 Inhibidora , Hígado/enzimología , Masculino , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/enzimología , Fenacetina/farmacocinética , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
To investigate how cognitive impairment is affected by the relief of bilateral carotid stenosis, chronic cerebral hypoperfusion was established through stenosis of the bilateral carotid common artery in adult Sprague-Dawley rats. Subsequently, the model rats received the intragastric placebo, donepezil (5 mg per kg), or surgery to relieve carotid stenosis after bilateral carotid common artery stenosis. After carotid stenosis was relieved, the cerebral blood flow values significantly increased, and P300 latency and escape latency in the Morris water-maze were significantly shortened. The concentrations of acetylcholine and norepinephrine in the dorsal hippocampus increased after carotid stenosis was relieved. Furthermore, P300 latency and escape latency were shortened in the relief-treated group compared to the drug-treated group, and acetylcholine levels in the relief-treated group were higher than the drug-treated group. No significant difference was found for the norepinephrine levels in the dorsal hippocampus between the relief-treated and drug-treated groups. Cognitive impairment can be significantly reduced by bilateral carotid stenosis relief, and the effect of relieving stenosis on cognitive dysfunction is superior to the effect of administering an acetylcholinesterase inhibitor.
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Isquemia Encefálica/complicaciones , Arterias Carótidas/fisiopatología , Estenosis Carotídea/complicaciones , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/terapia , Acetilcolina/metabolismo , Estimulación Acústica/métodos , Análisis de Varianza , Animales , Monoaminas Biogénicas/metabolismo , Estenosis Carotídea/tratamiento farmacológico , Estenosis Carotídea/cirugía , Circulación Cerebrovascular/efectos de los fármacos , Circulación Cerebrovascular/fisiología , Inhibidores de la Colinesterasa/uso terapéutico , Modelos Animales de Enfermedad , Donepezilo , Potenciales Relacionados con Evento P300/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Indanos/uso terapéutico , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Microdiálisis , Piperidinas/uso terapéutico , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
<p><b>OBJECTIVE</b>To observe clinical efficacy of Huazhuo Jiedu Recipe (HJR) on chronic atrophic gastritic precancerosis (CAGP), and its effect on contents of lactic acid, total acid, free acid, and nitrite in the gastric juice, as well as tumor markers in gastric juice and blood.</p><p><b>METHODS</b>Two hundred and twenty-nine patients with CAGP were randomly assigned to two groups, the 119 patients in the treated group orally took HJR and the 110 patients in the control group orally took Weifuchun Tablet. The therapeutic course for all was three months, two courses in total. The therapeutic efficacy, changes of gastric acid contents before and after treatment were observed, and the tumor markers in the gastric juice and blood were detected using electrochemical luminescence immunoassay.</p><p><b>RESULTS</b>The pathological effective rate was 83.2% (99/119) in the treated group and 60.9% (67/110) in the control group, showing significant difference between the two groups (P <0.05). The total acids and free acids in the gastric juice were significantly improved, contents of lactic acid and nitrite were significantly lowered in the two groups. Both contents of carcinoembryonic antigen (CEA), carbohydrate antigen19-9 (CA19-9), carbohydrate antigen72-4 (CA72-4), and carbohydrate antigen125 (CA125) in the gastric juice and serum were significantly lowered after treatment in the treated group (P<0.05). Compared with the normal control group, the therapeutic effect was more obvious in the treated group (P<0.05).</p><p><b>CONCLUSIONS</b>HJR could stimulate the gastric membranous secretion, enhance contents of total acids and free acids. It could prevent the further progress of CAGP by decreasing contents of lactic acid and nitrite in the gastric juice, and lowering contents of CEA, CA19-9, CA72-4, and CA125 in the gastric juice and serum.</p>
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Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Biomarcadores de Tumor , Sangre , Medicamentos Herbarios Chinos , Farmacología , Usos Terapéuticos , Jugo Gástrico , Química , Gastritis Atrófica , Sangre , Metabolismo , Fitoterapia , Lesiones Precancerosas , Sangre , Metabolismo , Neoplasias Gástricas , Sangre , MetabolismoRESUMEN
OBJECTIVE: To observe and compare the protective effect of garlic oil against carbon tetrachloride (CCL)-induced acute liver injury. METHODS: The experiments include 4 preventive groups and 2 therapeutic groups. In every preventive and therapeutic group, the mice were randomized into 6 groups with 15 each, including one negative control group, one solvent control group, one CCl4 model group and 3 garlic oil groups (25, 50, and 100 mg/kg body weight). Before given a single gavage of CCl4 (80 mg/kg), the mice were pretreated with garlic oil by gavage in preventive group 1 (30 days, once daily), preventive group 2 (5 days, once daily), preventive group 3 (ahead of 2 h, once), preventive group 4 (immediately, once) or the vehicle (corn oil, 10 ml/kg) in solvent control group. In therapeutic groups, the mice were gavaged garlic oil 2 h (once, in therapeutic 1) or for 5 days (once daily, in therapeutic 2) after administration CCl. After 24 h of the last administration, blood was collected and centrifuged at 2500 r/min at 4 degrees C for 10 min, and serum was removed to measure ALT and AST activities. The liver was dissected, weighed to calculate the liver coefficient (relative liver weight). At the same time, the liver samples were studied by histological examinations. RESULTS: Compared with negative group, the liver coefficient and the activities of ALT and AST in serum of model group were increased remarkably (P < 0.01). Compared with CCl model group, the liver coefficient and the activities of ALT and AST in serum were decreased significantly (P < 0.01) by garlic oil dose-dependently in each preventive group. Simultaneously, histological assessment showed that garlic oil effectively alleviated hepatocyte injuries induced by CCl4. Comparing the preventive effects of garlic oil in every group, it was better in preventive group 3 than others. However, all indexes and histological examinations in therapeutic group 1 did not show the difference with those of CCl4 model group. In therapeutic group 2, all indexes recovered after 5 d of CCl4 administration. CONCLUSIONS: Garlic oil can prevent acute liver injury induced by CCl4 and the effect is better in ahead of 2 h group than others.