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OBJECTIVE: To preliminary investigate the distribution of Traditional Chinese Medicine (TCM) constitution among patients with allergic rhinitis (AR) and reveal the related factors with anxiety and depression. METHODS: Between July 2020 and June 2021, specialist doctor recruited AR patients in Beijing and Shanghai. A total of 630 patients admitted to participate in the survey, and 516 (81.9%) (male 54.3%, female 45.7%) participants completed the questionnaires. Three scales including Constitution in Chinese Medicine Questionnaire (CCMQ), Generalized Anxiety Disorder Questionnaire (GAD-7) and The Patient Health Queationaire-9 (PHQ-9) were applied. The χ2 and the Fisher's exact test were used to evaluate the classification data, multivariate logistic regression was used to explore the related factors of anxiety and depression. RESULTS: According to 516 AR patients, the most commonly first-constitution was Yang-deficiency (22.1%) and frequent of all constitutions was inherited-special (21.6%). One third of AR patients (33.5%) suffered from anxiety, nearly half of AR patients (46.5%) were found to be depressive. Inherited-special (27.7%) was the most common constitution in patients with anxiety whereas Yang-deficiency (26.7%) was most common constitution in patients with depression. Sex, duration of symptoms, balanced, Qi-deficiency, phlegm-dampness, Qi-stagnation, and inherited-special constitutions were related with anxiety; Sex, income, duration of symptoms, balanced, Qi-deficiency, Yang-deficiency, phlegm-dampness, Qi-stagnation, and inherited-special constitutions were related with depression. CONCLUSIONS: According to our study, the commonly constitution types of AR were Yang-deficiency and inherited-special. We found that the prevalence value of anxiety and depression were high. People with Qi-deficiency, phlegm-dampness, Qi-stagnation, and inherited-special constitutions were more likely to have mental problems than the others. Controlling these influential factors might be beneficial for clinical health management of AR patients, and the government should apply appropriate mental health treatment services to offer psychiatric support.
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Depresión , Medicina Tradicional China , Humanos , Masculino , Femenino , Depresión/epidemiología , Constitución Corporal , China/epidemiología , Deficiencia Yang , Ansiedad/epidemiología , Trastornos de AnsiedadRESUMEN
Idiopathic pulmonary fibrosis is incurable, and its progression is difficult to control and thus can lead to pulmonary deterioration. Pan-histone deacetylase inhibitors such as SAHA have shown potential for modulating pulmonary fibrosis yet with off-target effects. Therefore, selective HDAC inhibitors would be beneficial for reducing side effects. Toward this goal, we designed and synthesized 24 novel HDAC6, HDAC8, or dual HDAC6/8 inhibitors and established a two-stage screening platform to rapidly screen for HDAC inhibitors that effectively mitigate TGF-ß-induced pulmonary fibrosis. The first stage consisted of a mouse NIH-3T3 fibroblast prescreen and yielded five hits. In the second stage, human pulmonary fibroblasts (HPFs) were used, and four out of the five hits were tested for caco-2 permeability and liver microsome stability to give two potential leads: J27644 (15) and 20. This novel two-stage screen platform will accelerate the discovery and reduce the cost of developing HDAC inhibitors to mitigate TGF-ß-induced pulmonary fibrosis.
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Inhibidores de Histona Desacetilasas , Fibrosis Pulmonar Idiopática , Ratones , Animales , Humanos , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Histona Desacetilasas/uso terapéutico , Factor de Crecimiento Transformador beta , Histona Desacetilasas/uso terapéutico , Evaluación Preclínica de Medicamentos , Células CACO-2 , Fibrosis Pulmonar Idiopática/inducido químicamente , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Histona Desacetilasa 6 , Proteínas RepresorasRESUMEN
OBJECTIVE@#To investigate the therapeutic effects of total saponins from Panax notognseng (PNS) combined with cyclophosphamide (CTX) in mice bearing hepatocellular carcinoma H22 cell xenograft.@*METHODS@#We examined the effects of treatment with different concentrations of PNS on H22 cell proliferation for 24 to 72 h in vitro using CCK8 colorimetric assay. Annexin V/PI double fluorescence staining was used to detect the effect of PNS on apoptosis of H22 cells. Mouse models bearing H22 cell xenograft were established and treated with CTX (25 mg/kg), PNS (120, 240 or 480 mg/kg), alone or in combinations. After treatments for consecutive 10 days, the mice were euthanized for examinations of carbon clearance ability of the monocytes and macrophages, splenic lymphocyte proliferation, tumor necrosis factor (TNF-α), interleukin-2 (IL-2), serum hemolysin antibody level, blood indicators, and the tumor inhibition rate.@*RESULTS@#Treatment with PNS concentration-dependently inhibited the proliferation and significantly promoted apoptosis of cultured H22 cells (P < 0.01). In the tumor-bearing mouse models, PNS alone and its combination with CTX both resulted in obvious enhancement of phagocytosis of the monocyte-macrophages, stimulated the proliferation of splenic lymphocytes, promoted the release of TNF-α and IL-2 and the production of serum hemolysin antibody, and increased the number of white blood cells, red blood cells and lymphocytes in the peripheral blood. Treatment with 480 mg/kg PNS combined with CTX resulted in a tumor inhibition rate of 83.28% (P < 0.01) and a life prolonging rate of 131.25% in the mouse models (P < 0.05).@*CONCLUSION@#PNS alone or in combination with CTX can improve the immunity and tumor inhibition rate and prolong the survival time of H22 tumor-bearing mice.
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Animales , Humanos , Ratones , Carcinoma Hepatocelular/patología , Ciclofosfamida/uso terapéutico , Proteínas Hemolisinas , Xenoinjertos , Interleucina-2 , Neoplasias Hepáticas/patología , Panax notoginseng , Saponinas/uso terapéutico , Factor de Necrosis Tumoral alfaRESUMEN
Objective::To finding the main research contents, research frontier, author and institutional cooperation of traditional Chinese medicine(TCM) for treating henoch-schonlein purpura(HSP). Providing reference for the research and development of TCM for treating the disease. Method::Using Citespace to analyze 2 878 TCM articles related to HSP retrieved from CNKI, cluster analysis and burst analysis of literature keywords, co-occurring authors and institutional cooperation analysis. Result::Since 1995, the number of related literature was growing rapidly and had been stable at more than 100 per year after 2005.Cluster analysis showed 32 clusters, consisting of 396 nodes and 638 lines. The main clustering results include Children with allergic purpura, blood-activating and stasis-resolving drug, Henoch-Schonlein purpura nephritis, blood-cooling drugs, clinical observation, etc. Break analysis yielded 52 emergent words. It can be seen that TCM treatment of HSP is mainly based on cooling blood, followed by activating blood to eliminate stagnation and clearing heat. Commonly used drugs are Moutan Cortex, Paeoniae Radix Rubra, and Rehmanniae Radix, etc. Clinically, it pays more attention to the experience of famous doctors, research on Children with allergic purpura, etc.The author's cooperation network has obtained the maps of the three main cooperation teams with DING Ying, SUN Yi-qiu and HE Ping as the core. The Density of institutional cooperation network is 0.007 1. Conclusion::The main research contents of TCM for treating HSP include Children with allergic purpura, blood-activating and stasis-resolving drug, HSP nephritis, blood-cooling drugs, clinical observation, etc. Children with allergic purpura, experience from famous doctor, HSP nephritis and clinical efficacy is the foremost current research hotspot. A number of research teams have been formed that are relatively stable, but the institutional cooperation is scattered.
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To explore the medication rules of herbal prescriptions for nonalcoholic fatty liver disease,and analyze the possible drug targets and interactions,in order to explore the mechanisms of the herbs. Randomized controlled trials of herbal prescriptions for treating nonalcoholic fatty liver disease were collected from CNKI,Wan Fang,VIP,Sino Med and PubMed databases. The properties,flavors and meridian tropism of herbs were analyzed by using systematic cluster analysis method with SPSS 19. 0 software. Subsequently,the association rules of herbs were analyzed by using Clementine 12. 0 software. Finally,the interactions between targets and relevant signaling pathways were analyzed by Traditional Chinese Medicine Systems Pharmacology Database(TCMSP),Search Tool for the Retrieval of Interacting Genes/Proteins(STRING) and Kyoto Encyclopedia of Genes and Genomes(KEGG). In the 88 prescriptions screened out,the commonly used herbs were Salvia miltiorrhiza,Bupleurum chinense,Alisma orientale,and Crataegus pinnatifida,and the potential signaling pathways were PPAR signaling pathway and calcium signaling pathway. The results showed that the main effects of herbal prescriptions were to improve blood flow/clear blood stasis,clear heatiness/dampness,promote digestion and strengthen spleen. And its mechanism of action may be achieved through the regulation of PPAR signaling pathway and calcium signaling pathway.
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Humanos , Minería de Datos , Medicamentos Herbarios Chinos , Usos Terapéuticos , Medicina Tradicional China , Meridianos , Enfermedad del Hígado Graso no Alcohólico , Quimioterapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Transducción de SeñalRESUMEN
Health medicine has been the direction of the development of medicine. However, the definition of health defined by Western medicine and traditional medicine cannot completely cover the full meaning of health. Therefore, we propose the new concept of health: health is a state of physical and mental harmony of different individuals in the life process with the environment, and good self-adaptive and regulation ability to natural and social environment. The new concept of health enriches the connotation of health defined by Western medicine and improves the understanding of health in the past, which provide the conceptual basis for further study on health medicine.
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Ginkgo diterpene lactones meglumine injection (GDLI) is a commercially available product used for neuroprotection. However, the pharmacokinetic properties of the prototypes and hydrolyzed carboxylic forms of the primary components in GDLI, i.e., ginkgolide A (GA), ginkgolide B (GB), and ginkgolide K (GK), have never been fully evaluated in beagle dogs. In this work, a simple, sensitive, and reliable method based on ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) was developed, and the prototypes and total amounts of GA, GB, and GK were determined in beagle dog plasma. The plasma concentrations of the hydrolyzed carboxylic forms were calculated by subtracting the prototype concentrations from the total lactone concentrations. For the first time, the pharmacokinetics of GA, GB, and GK were fully assessed in three forms, i.e., the prototypes, the hydrolyzed carboxylic forms, and the total amounts, after intravenous administration of GDLI in beagle dogs. It was shown that ginkgolides primarily existed in the hydrolyzed form in plasma, and the ratio of hydrolysates to prototype forms of GA and GB decreased gradually to a homeostatic ratio. All of the three forms of the three ginkgolides showed linear exposure of AUC to the dosages. GA, GB, and GK showed a constant half-life approximately 2.7, 3.4, and 1.2 h, respectively, which were consistent for the forms at three dose levels (0.3, 1.0, and 3.0 mg·kg) and after a consecutive injection of GDLI for 7 days (1.0 mg·kg).
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Animales , Perros , Ginkgo biloba , Química , Ginkgólidos , Farmacocinética , Lactonas , Farmacocinética , Extractos Vegetales , Farmacocinética , Espectrometría de Masas en TándemRESUMEN
This article discussed the feasibility of assessing health state by detecting redox state of human body. Firstly, the balance of redox state is the basis of homeostasis, and the balance ability of redox can reflflect health state of human body. Secondly, the redox state of human body is a sensitive index of multiple risk factors of health such as age, external environment and psychological factors. It participates in the occurrence and development of multiple diseases involving metabolic diseases and nervous system diseases, and can serve as a cut-in point for treatment of these diseases. Detecting the redox state of high risk people is signifificantly important for early detection and treatment of disease. The blood plasma and urine could be selected to detect, which is convenient. It is pointed that the indexes not only involve oxidation product and antioxidant enzyme but also redox couple. Chinese medicine constitution reflflects the state of body itself and the ability of adapting to external environment, which is consistent with the connotation of health. It is found that there are nine basic types of constitution in Chinese population, which provides a theoretical basis of health preservation, preventive treatment of disease and personalized treatment. With the combination of redox state detection and the Chinese medicine constitution theory, the heath state can be systemically assessed by conducting large-scale epidemiological survey with classifified detection on redox state of human body.
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Humanos , Enfermedad , Estudios de Factibilidad , Estado de Salud , Cuerpo Humano , Medicina Tradicional China , Oxidación-ReducciónRESUMEN
Isochlorogenic acid A (ICQA), which has anti-inflammatory, hepatoprotective, and antiviral properties, is commonly presented in fruits, vegetables, coffee, plant-based food products, and herbal medicines. These herbal medicines are usually used in combination with other medicines in the clinic. However, little is known about the regulatory effects of ICQA on drug-metabolizing enzymes and the herb-drug interactions. In the present study, we evaluated the inhibitory potentials of ICQA on CYP1A2, CYP2C9, CYP2C19, CYP3A4, CYP2D6, and CYP2E1 in vitro based on a cocktail approach. The P450 and UGT activities in mice treated with ICQA for a prolonged period were also determined. Our results demonstrated that ICQA exhibited a weak inhibitory effect on CYP2C9 in human liver microsomes with IC being 57.25 μmol·L and Ki being 26.77 μmol·L. In addition, ICQA inhibited UGT1A6 activity by 25%, in the mice treated with ICQA (i.p.) at 30 mg·kg for 14 d, compared with the control group. Moreover, ICQA showed no mechanism-based inhibition on CYP2C9 or UGT1A6. In conclusion, our results further confirm a safe use of ICQA in clinical practice.
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Animales , Humanos , Ratones , Ácido Clorogénico , Química , Inhibidores Enzimáticos del Citocromo P-450 , Química , Sistema Enzimático del Citocromo P-450 , Química , Metabolismo , Glucuronosiltransferasa , Química , Metabolismo , Cinética , Ratones Endogámicos C57BL , Microsomas Hepáticos , QuímicaRESUMEN
Glycyrrhizin is a major bioactive component of liquorice, which exerts multiple biochemical and pharmacological activities and is frequently used in combination with other drugs in the clinic. Mycophenolate mofetil (MMF), an immunosuppressant widely used in transplant patients, is metabolized by UDP-glucuronyltransferases (UGTs). Although significant evidence supports that glycyrrhizin could interact with the cytochrome P450s (CYPs), few studies have addressed its effects on UGTs. The present study aimed at investigating the regulatory effects of diammonium glycyrrhizinate (GLN) on UGTs in vitro and in vivo. We found that long-term administration of GLN in rats induced overall metabolism of MMF, which might be due to the induction of UGT1A protein expression. Hepatic UGT1A activity and UGT1A mRNA and protein expression were significantly increased in GLN-treated rats. UGT1A expression levels were also increased in the intestine, contradicting with the observed decrease in intestinal UGT1A activities. This phenomenon may be attributed to different concentrations of glycyrrhetinic acid (GA) in liver and intestine and the inhibitory effects of GA on UGT1A activity. In conclusion, our study revealed that GLN had multiple effects on the expression and activities of UGT1A isoforms, providing a basis for a better understanding of interactions between GLN and other drugs.
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Animales , Masculino , Ratas , Medicamentos Herbarios Chinos , Química , Farmacología , Glucuronosiltransferasa , Química , Metabolismo , Ácido Glicirrínico , Química , Farmacología , Interacciones de Hierba-Droga , Intestinos , Química , Cinética , Hígado , Química , Ratas Sprague-DawleyRESUMEN
Liquid chromatography hybrid ion trap/time-of-flight mass spectrometry possessesd both the MS(n) ability of ion trap and the excellent resolution of a time-of-flight, and has been widely used to identify drug metabolites and determine trace multi-components for in natural products. Collision energy, one of the most important factors in acquiring MS(n) information, could be set freely in the range of 10%-400%. Herein, notoginsenosides were chosen as model compounds to build a novel methodology for the collision energy optimization. Firstly, the fragmental patterns of the representatives for the authentic standards of protopanaxadiol-type and protopanaxatriol-type notoginsenosides authentic standards were obtained based on accurate MS(2) and MS(3) measurements via liquid chromatography hybrid ion trap/time-of-flight mass spectrometry. Then the extracted ion chromatograms of characteristic product ions of notoginsenosides in Panax Notoginseng Extract, which were produced under a series of collision energies and, were compared to screen out the optimum collision energies values for MS(2) and MS(3). The results demonstrated that the qualitative capability of liquid chromatography hybrid ion trap/time-of-flight mass spectrometry was greatly influenced by collision energies, and 50% of MS(2) collision energy was found to produce the highest collision-induced dissociation efficiency for notoginsenosides. BesidesAddtionally, the highest collision-induced dissociation efficiency appeared when the collision energy was set at 75% in the MS(3) stage.
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Cromatografía Líquida de Alta Presión , Métodos , Medicamentos Herbarios Chinos , Química , Ginsenósidos , Química , Espectrometría de Masas , Métodos , Estructura MolecularRESUMEN
The aim of the study is to evaluate the effects of the single and mixed decoction of Thallus laminariae (kelp) and Glycyrrhiza glabra (licorice) on the metabolism and their difference. The mixed decoction of kelp and licorice and the single decoction were made and intragastrically administered to the SD rats. The effect on system metabolism, the toxicity of liver and kidney were assessed by GC-MS profiling of the endogenous molecules in serum, routine biochemical assays and histographic inspection of tissues from SD rats, separately. The mixed decoction of kelp and licorice induced more obvious pathological abnormalities in SD rats than a single decoction of kelp, while the extracts of licorice did not show any pathological change. Neither the mixed, nor the single decoction showed abnormal histopathology. After intragastric administration of extracts for 5 days, the mixed decoction induced a decrease of ALT (no significant change in the groups of single decoction) and an increase of BUN (so did the single decoction of kelp). Metabolomic profile of the molecules in serum revealed that the metabolic patterns were all obviously affected for the three groups, i.e., the mixed and single decoction of kelp and licorice. The rats given with the single decoction of kelp showed a similar pattern to that of the mixed decoction, indicating that the kelp primarily contributed the perturbation of metabolism for the mixed decoction. All three groups induced a decrease of branched chain amino acids, TCA cycle intermediates and glycolysis intermediates (e.g., pyruvic acid and lactic acid) and an increase of 3-hydroxybutyric acid. Kelp decoction showed stronger potential in reducing TCA cycle intermediates and glycolysis intermediates than the other two groups, while the levels of branched chain amino acids were the lowest after licorice extracts were given. These results suggested that the effect of the mixed decoction on metabolism was closely associated with both kelp and licorice. The continuous administration of single decoction of kelp and the mixed decoction of licorice and kelp resulted in pathological abnormalities in kidney of SD rats. The mixed decoction of kelp and licorice distinctly perturbed sera molecules and hence system metabolism, which showed associated with those of kelp and licorice. Although the metabolic effect was associated with both kelp and licorice, the results suggested kelp contributed to it primarily.
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Animales , Ratas , Glycyrrhiza , Química , Kelp , Química , Riñón , Hígado , Metabolómica , Preparaciones de Plantas , Farmacología , Ratas Sprague-DawleyRESUMEN
As a computer-assisted approach, molecular docking has been universally applied in drug research and development and plays an important role in the investigation and evaluation of herbal medicines. Herein, the method was used to estimate the pharmacodynamics of Mai-Luo-Ning injection, a traditional Chinese compound herbal prescription. Through investigating the interactions between several important proteins in cardiovascular system and characteristic components of the formula, its effect on cardiovascular protection was evaluated. Results showed the differences in the interactions between each component and the selected target proteins and revealed the possible mechanisms for synergistic effects of various characteristic components on cardiovascular protection. The study provided scientific evidence supporting the mechanistic study of the interactions among multi-components and targets, offering a general approach to investigating the pharmacodynamics of complicated materials in compound herbal prescriptions.
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Humanos , Fármacos Cardiovasculares , Farmacología , Sistema Cardiovascular , Metabolismo , Sinergismo Farmacológico , Medicamentos Herbarios Chinos , Farmacología , Enzimas , Metabolismo , Simulación del Acoplamiento MolecularRESUMEN
Constitution factor plays an important role in the occurrence, development, and transformation of diseases. The occurrence of allergic diseases is mainly caused by the disorganized physiological function and suitability regulation of patients, except for their exposure to outside allergens. Moreover, it represents susceptibility and hypersensitivity to allergens. The current study expresses the concept of allergic constitution from the perspective of Chinese medicine (CM) and presents the criterion of allergic constitution. In addition, the distribution of allergic constitution in population, its factors, and its relation to health-related quality of life (HRQOL) were investigated. The HRQOL scores of allergic constitution were found to be lower than those of the Pinghe constitution. After making a study on the gene expression profile of allergic constitution, the characteristics of up-regulated or down-regulated genes were found. Finally, CM drug was researched and developed to improve allergic constitution. Based on clinical trials and animal experiments, CM is found to have good regulatory effects on allergic constitution.
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Animales , Humanos , Perfilación de la Expresión Génica , Hipersensibilidad , Epidemiología , Genética , Psicología , Terapéutica , Medicina Tradicional ChinaRESUMEN
Translational medicine is a new concept presented in recent decades, the core of which is to build a bridge between basic medical research and clinical application. From the beginning of constitution of Chinese medicine, clinical application has been given priority. Therefore, the idea of translational medicine is fully demonstrated in the research into the three key scientific problems of "classification of constitution of Chinese medicine", "relationship between constitution and disease" and "adjustment of constitution". Under its guidance, not only was the systematic theory of constitution of Chinese medicine established, but also the Constitution of Chinese Medicine Scale and the Standards of Classification and determination of Constitution of Chinese Medicine were developed, which translates methods of classifying the nine constitutional types into guidance for prevention of disease, management of health and clinical application. The research findings of constitution of Chinese medicine have been applied in clinical practice and public health, establishing the diagnosis and treatment model of constitution-disease-syndrome differentiation. The nationwide application of constitution differentiation has shown good effect. In the future, constitution of Chinese medicine should strengthen the evidence-based research and multi-disciplinary cooperation, and establish a research team on comprehensive constitution of Chinese medicine and translational medicine, to translate the findings into clinical practice and public health more accurately and quickly.
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Humanos , Investigación Biomédica , Medicina Tradicional China , Síndrome , Investigación Biomédica Traslacional , Estados Unidos , United States Public Health ServiceRESUMEN
<p><b>OBJECTIVE</b>To study the expression changes of tumor necrosis factor-alpha (TNF-(alpha), interleukin-6 (IL-6), C-reactive protein (CRP), monocyte chemotactic protein 1 (MCP-1), and their correlation with obesity in 20 -50 years old population of phlegm-damp constitution (PDC) and of normal constitution (NC) using Luminex technique.</p><p><b>METHODS</b>Totally 101 population were recruited from Health Examination Center of Puren Hospital from April to December 2011. Based on body mass index (BMI), the subjects were assigned to four groups, i.e., the obesity of PDC group (Group OBT, BMI > or = 24 kg/m2, 30 cases), the non-obesity of PDC group (Group NOBT, BMI < 24 kg/m2, 25 cases), the obesity of non-PDC group (Group OBNT, BMI > or = 24 kg/m2, 28 cases), the NC group (Group P, BMI < 24 kg/m2, 18 cases). The BMI and body fat percent (FAT%) were compared among the 4 groups. Serum levels of TNF-alpha, IL-6, CRP, and MCP-1 were measured with Luminex technique.</p><p><b>RESULTS</b>BMI was significantly higher in Group OBT and Group OBNT than in Group NOBT and Group P (all P < 0.05). The FAT% was significantly higher in Group OBT and Group OBNT than in Group P (P < 0.01). The serum TNF-alpha level in Group OBT was higher than in Group P (P < 0.01). The serum CRP and MCP-1 levels were significantly higher in Group OBT, NOBT, and OBNT than in Group P (P < 0.05, P < 0.01). The score for PDC was positively correlated with TNF-alpha, IL-6, and MCP-1 levels (P < 0.05).</p><p><b>CONCLUSIONS</b>Abnormal higher levels of inflammatory factors exist in 20 -50 years old population of PDC. Chronic inflammation exists in population of PDC and obesity people.</p>
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Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Índice de Masa Corporal , Proteína C-Reactiva , Metabolismo , Estudios de Casos y Controles , Quimiocina CCL2 , Sangre , Inflamación , Interleucina-6 , Sangre , Medicina Tradicional China , Procedimientos Analíticos en Microchip , Obesidad , Sangre , Diagnóstico , Factor de Necrosis Tumoral alfa , SangreRESUMEN
Drug metabolism studies, including in vivo and in vitro metabolism studies, are significant in the design of candidate compounds and screening of lead compounds at drug discovery/development stages. Compared with in vivo metabolism studies, in vitro metabolism studies have the advantages of rapidity, simplicity, without consumption of large amounts of samples and animals. Moreover, it is convenient for researchers to observe the selective interaction between compound and target. Therefore, in vitro metabolism studies are appropriate for high throughput screening of compounds which are lack of metabolism information and have been widely used during drug discovery stages. This article briefly introduced the application of in vitro drug metabolism studies based on the metabolic stability, reaction phenotyping and metabolic drug-drug interactions, aiming to raise valuable evaluation strategies for innovative drug discovery in China.
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Animales , Humanos , Sistema Enzimático del Citocromo P-450 , Metabolismo , Diseño de Fármacos , Descubrimiento de Drogas , Métodos , Evaluación Preclínica de Medicamentos , Interacciones Farmacológicas , Estabilidad de Medicamentos , Glucuronosiltransferasa , Metabolismo , Preparaciones Farmacéuticas , Metabolismo , FenotipoRESUMEN
OBJECTIVE@#To analyze the effect of intestinal function-recovering decoction on multiple organ dysfunction syndrome in rats, and to investigate a novel solution to multiple organ dysfunction syndrome.@*METHODS@#Multiple organ dysfunction syndrome was induced in 60 Sprague-Dawley rats by intestinal ischemia-reperfusion combined with cecal ligation and puncture. Then these rats were intragastrically administered physiological saline (group I, n=20), ampicillin (group II, n=20) or intestinal function-recovering decoction (group III, n=20). After treatment, serum malondialdehyde and superoxide dismutase levels were compared among three groups. Simultaneously, bacterial culture of various organ tissues was performed and bacterial and endotoxin translocation were observed.@*RESULTS@#Compared with group I, serum malondialdehyde, alanine aminotransferase and aspartate aminotransferase levels were significantly decreased (all P0.05). The rate of bacterial translocation in the groups II and III was significantly lower than in the group I (P0.05).@*CONCLUSIONS@#Intestinal function-recovering decoction can significantly reduce endotoxin and bacterial translocation and stabilize enteral oxidative-antioxidative balance.
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Animales , Femenino , Masculino , Ratas , Ampicilina , Farmacología , Antibacterianos , Farmacología , Traslocación Bacteriana , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Farmacología , Endotoxinas , Sangre , Mucosa Intestinal , Microbiología , Malondialdehído , Sangre , Insuficiencia Multiorgánica , Quimioterapia , Microbiología , Ratas Sprague-Dawley , Superóxido Dismutasa , SangreRESUMEN
AIM@#Silybin (SB), a major constituent of the milk thistle, has been used to treat several liver disorders. However, liver diseases were always accompanied by CYP450 dysfunction. This study was designed to explore the relationship between the hepatoprotective effect and CYP3A regulation of SB during thioacetamide (TAA)-induced rat liver injury.@*METHODS@#Serum biochemical analysis and histopathological study were taken to evaluate the hepatoprotectinve effect of SB. α-SMA were detected by immunohistochemical analysis and cytokine release in rat liver was determined by ELISA assay. CYP3A and PXR expression were determined by RT-PCR and Western blot analysis, and CYP3A activity was based on the midazolam 4-hydroxylation reaction. Also, siRNA transfection was induced in HepG2 cells to evaluate the effect of PXR on cytotoxicity and CYP3A4 dysregulation caused by TAA.@*RESULTS@#SB showed powerful hepatoprotective effects, and anti-inflammatory and anti-fibrosis effects, and reversed the loss of CYP3A and PXR in TAA-injured rat liver, and decreased PXR translocation into the cell nucleus. PXR silencing weakened the effect of SB on cytoprotection and CYP3A regulation.@*CONCLUSIONS@#PXR was a very important factor of CYP3A regulation and might be the target of SB in TAA-induced liver disease. Also, because of the potential interactions of SB and co-administered medicines, it might be necessary to adjust the dosage in the clinical medication of liver disease.
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Animales , Masculino , Ratas , Enfermedad Hepática Inducida por Sustancias y Drogas , Quimioterapia , Citocromo P-450 CYP3A , Genética , Metabolismo , Medicamentos Herbarios Chinos , Hígado , Metabolismo , Silybum marianum , Química , Receptor X de Pregnano , Ratas Sprague-Dawley , Receptores de Esteroides , Genética , Metabolismo , Transducción de Señal , Silimarina , Silimarina , TioacetamidaRESUMEN
The main objective of the current study was to develop a universal method for a protein binding assay of complicated herbal components, and to investigate the possible relationship between compound polarity and protein binding using Schisadra lignans as an example. Firstly, the rat, dog and human plasma were spiked with three different concentrations of Schisandra chinensis extract (SLE), and ultramicrofiltration was used to obtain the unbound ingredients. Secondly, thirty-one Schisandra lignans in total plasma and ultrafiltered fluid were measured by LC-IT-TOFMS. Lastly, a relative exposure approach, which entailed calculating the relative concentrations of each Schisandra lignan from the corresponding calibration equation created from the calibration samples spiked with the stock solution of SLE, was applied in order to overcome the absence of authentic standards. The results showed that Schisandra lignans exhibited a high capability to bind with plasma protein, furthermore, the protein binding ratio of the lignan components increased proportionally with their individual chromatographic retention time, which indicated that the ratio of protein binding of lignans might increase accordingly with decreasing polarity. This study suggested that the compound polarity might be an important factor affecting the plasma protein binding of herbal components.