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Objective To explore the molecular mechanism of Xiaojin Pills in the treatment of breast cancer using an integrated network pharmacology and experimental verification.Methods The chemical components and potential targets of Xiaojin Pills were obtained from TCMSP,TCM-ID,ETCM and SwissTargetPrediction databases.Breast cancer related targets were collected from GeneCards,OMIM and KEGG databases.The overlapped targets were imported into STRING database to analysis a protein-protein interaction(PPI).The key targets of PPI networks were screened based on node topology parameter values through Cytoscape 3.8.0.DAVID database was used to analyze the GO and KEGG pathway enrichment to build drug-chemical components-key targets-signaling pathway network.The breast cancer cell lines MDA-MB-231 and SK-BR-3 were used to study the effects of Xiaojin Pills extract on cell apoptosis,migration and invasion,and to verify the key pathway obtained by enrichment analysis.Results Totally 181 chemical components in Xiaojin Pills were obtained,including quercetin,myricetin,pinocembrin and β-sitosterol.615 potential targets were identified for the anti-breast cancer effects of Xiaojin Pills.After overlapping,170 key targets against breast cancer were identified based on the topological analysis,which included SRC,ERK1/2,AKT1,EGFR,etc.KEGG analysis enriched pathways including pathways in cancer,MAPK signaling pathway,endocrine resistance,PI3K-AKT signaling pathway,EGFR tyrosine kinase inhibitor resistance,apoptosis,and HIF-1 signaling pathway,which may play important roles in the therapeutic effects of Xiaojin Pills against breast cancer.GO enrichment was involved in protein phosphorylation,inflammatory response,negative regulation of apoptosis,and positive regulation of ERK1 and ERK2 cascades.Cell experiments showed that Xiaojin Pills further induced mitochondria-dependent apoptosis by inhibiting the activation of MAPK and PI3K-AKT pathways.At the same time,the expressions of ZO-1 and β-catenin increased,and the epithelial-mesenchymal transformation process was reversed to inhibit the metastasis of breast cancer cells.Conclusion The key targets and signaling pathways of Xiaojin Pills in the treatment of breast cancer are studied through network pharmacology combined with in vitro experiments,which provided a basis for further study of its pharmacodynamic material basis,mechanism of action and clinical application.
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Shiwei Longdanhua Granule (SWLDH) is a classic Tibetan medicine (TM) ranking in the top 20 Chinese patent medicines in prescription rate to treat respiratory diseases like pneumonia, acute and chronic tracheobronchitis, acute exacerbation of COPD and bronchial asthma in solution of inflammation, cough and phlegm obstruction in clinical practice. However, its systematic pharmacological mechanisms have not been elucidated yet. Here, we studied the therapeutic efficacy of SWLDH in treatment of acute respiratory diseases in BALB/c mice by comprehensive analysis of airway inflammation, oxidative stress, mucus hypersecretion, cough hypersensitivities and indicators associated with the development of chronic diseases. Our results show that SWLDH might exhibit its inhibitory effects on pulmonary inflammation by interference with arachidonic acid (AA) metabolism pathways. Oxidative stress that highly related to the degree of tissue injury could be alleviated by enhancing the reductive activities of glutathione redox system, thioredoxin system and the catalytic activities of catalase and superoxide dismutase (SOD) after SWLDH treatment. In addition, SWLDH could significantly abrogate the mucus hypersecretion induced bronchiole obstruction by inactivate the globlet cells and decrease the secretion of gel-forming mucins (MUC5AC and MUC5B) under pathological condition, demonstrating its mucoactive potency. SWLDH also showed reversed effects on the release of neuropeptides that are responsible for airway sensory hypersensitivity. Simultaneously observed inhibition of calcium influx, reduction in in vivo biosynthesis of acetylcholine and the recovery of the content of cyclic adenosine monophosphate (cAMP) might collaboratively contribute to cause airway smooth muscle cells (ASMCs) relexation. These findings indicated that SWLDH might exhibited antitussive potency via suppression of the urge to cough and ASMCs contraction. Moreover, SWLDH might affect airway remodeling. We found SWLDH could retard the elevation of TGF-ß1 and α-SMA, which are important indicators for hyperplasia and contraction during the progression of the chronic airway inflammatory diseases like COPD and asthma.
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Asma , Hipersensibilidad , Neumonía , Enfermedad Pulmonar Obstructiva Crónica , Ratones , Animales , Tos/inducido químicamente , Tos/tratamiento farmacológico , Lipopolisacáridos/metabolismo , Neumonía/inducido químicamente , Neumonía/tratamiento farmacológico , Neumonía/metabolismo , Moco/metabolismo , Asma/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Enfermedad Crónica , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Estrés Oxidativo , Mucina 5AC/metabolismoRESUMEN
Objective:To investigate the effects of Guiling Gao on body temperature, gastrointestinal motility, gastrointestinal hormones, Th1/Th2 cytokines and water metabolism in rats with damp-heat syndrome.Methods:Totally 60 SD rats were randomly divided into control group, model group, mosapride group, Guiling Gao low dose group (3.4 g/kg), medium dose group (6.8 g/kg) and high dose group (13.6 g/kg) according to random number table method, with 10 rats in each group. Except for the blank group, the other groups adopted the method of "environmental factors + fat and sweet diet + biological factors" to prepare the rat model of damp heat syndrome of febrile diseases. After modeling, they were administered by gavage for 7 days. During the experiment, the general state, body weight and body temperature were observed, the gastric residue rate of rats was calculated by weighing method, the intestinal propulsion rate of rats was calculated by charcoal propulsion method, and the levels of serum motilin (MTL), gastrin (GAS), somatostatin (SS), substance P (SP),IL-4 and interferon-γ (IFN-γ) were detected by ELISA, and the changes of aquaporin 3 (AQP3) mRNA transcription level were detected by real-time PCR.Results:Compared with the model group, the weight of rats in Guiling Gao high dose group increased after experiment of 22 days ( P<0.05), and body temperature of rats in Guiling Gao medium and high dose group decreased in 19-20 day ( P<0.01); and the gastric emptying rate and the small intestine propulsion rate of small intestine in Guiling Gao medium and high dose group increased significantly ( P<0.01 or P<0.05); the serum MTL, GAS and SP levels increased ( P<0.01 or P<0.05), and SS decreased ( P<0.01 or P<0.05) in the Guiling Gao medium and high dose groups; The levels of IL-4, IFN-γ and IFN-γ/IL-4 ratio decreased ( P<0.01); The expression of AQP3 mRNA (1.16 ± 0.25 vs. 0.23 ± 0.01) in the Guiling Gao high dose group was up-regulated ( P<0.01). Conclusions:Guiling Gao can effectively improve the activity state of damp-heat syndrome model rats caused by complex factors. This mechanism may be related to enhancing gastrointestinal movement, increasing gastrointestinal hormone secretion, restoring the dynamic balance of immune system Th1/Th2 and promoting the transport of water from intestinal cavity.
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ObjectiveTo investigate the detoxification mechanism of Chebulae Fructus, Glycyrrhizae Radix et Rhizoma and Prepared Aconiti Kusnezoffii Radix Cocta, and their effective components ellagic acid, liquiritin and aconitine based on cardiac cytochrome P450 (CYP450) system. MethodIn in vivo experiments, rats were randomly divided into control group, prepared Aconiti Kusnezoffii Radix Cocta group (0.25 g·kg-1), Chebulae Fructus group (0.252 g·kg-1), Glycyrrhizae Radix et Rhizoma group (0.25 g·kg-1) and combination group (0.25 g·kg-1 Chebulae Fructus+0.25 g·kg-1 Glycyrrhizae Radix et Rhizoma+0.25 g·kg-1 prepared Aconiti Kusnezoffii Radix Cocta, with prepared Aconiti Kusnezoffii Radix Cocta as standard). After 8 days of administration, creatine kinase (CK) and lactate dehydrogenase (LDH) in rats were detected to observe the pathological changes of heart tissue. Real-time PCR and Western blot were performed to detect the mRNA and protein expressions of CYP2J3, respectively. In in vitro experiments, control group, aconitine group, ellagic acid group, liquiritin group and combination group (aconitine+ellagic acid+liquiritin) were set, and their effects on cell number, DNA content, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were detected by high content analysis. The changes in the mRNA and protein expressions of CYP2J3 were also observed. ResultIn vivo experiments, compared with the control group, the prepared Aconiti Kusnezoffii Radix Cocta group had increased CK and LDH in serum (P<0.05, P<0.01), while the combination group had decreased activities of CK and LDH. Additionally, pathological staining results showed that Chebulae Fructus and Glycyrrhizae Radix et Rhizoma reduced the cardiac toxicity caused by prepared Aconiti Kusnezoffii Radix Cocta. Real-time PCR found that compared with the control group, prepared Aconiti Kusnezoffii Radix Cocta down-regulated the mRNA level of CYP2J3 (P<0.05), while up-regulated that expression when used in combination with Chebulae Fructus and Glycyrrhizae Radix et Rhizoma (P<0.01). The protein and mRNA translation levels were basically consistent. In vitro experiments, high content analysis revealed that there was a decrease in the cell number, DNA content and MMP fluorescence value of the aconitine group (P<0.01) and the combination group (P<0.05, P<0.01), and the fluorescence value of the combination group was higher than that of the aconitine group. Moreover, aconitine down-regulated the mRNA level of CYP2J3 (P<0.05), but the down-regulating ability of aconitine was reversed in the combination group (P<0.05). ConclusionThe detoxification mechanism of combined Chebulae Fructus, Glycyrrhizae Radix et Rhizoma and prepared Aconiti Kusnezoffii Radix Cocta is mainly that the combination of ellagic acid, liquiritin and aconitine can up-regulate the expression of CYP2J3, and promote the metabolism of arachidonic acid (AA) to produce epoxyeicosatrienoic acids (EETs), thus reducing the cardiac toxicity, and this effect may start from the transcriptional link.
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Objective To study computer toxicity prediction technology and predict the acute toxicity of Chinese materia medica; To provide a new way and method for safety evaluation of traditional Chinese medicine. Methods First, Mold2 software (version 2.0.0) was used to calculate molecular descriptors of 7409 chemical components. After preliminary screening of molecular descriptors, quantitative structure-activity relationship (QSAR) models were built up with Random Forest (RF) for screening the optimum prediction model. From the 83 kinds of toxic Chinese materia medica in Chinese Pharmacopoeia (2010 edition), acute toxicity of 60 kinds of Chinese materia medica reported from monomer structure (1692 chemical components) were under prediction.Results Totally 7409 pieces of data were obtained. When the descriptors were 52, RF modeling accuracy and Kappa were the highest, 0.712 and 0.436 respectively. Compound clusters were divided into 3 types according to optimum molecule descriptors (52). The accuracy and Kappa of the optimum model for the first type of compounds were 0.666 and 0.476 respectively; the accuracy and Kappa of the optimum model for the second type of compounds were 0.804 and 0.381 respectively; the accuracy and Kappa of the optimum model for the third type of compounds were 0.709 and 0.373 respectively. It was predicted that 60 kinds of Chinese materia medica containing 0 violent toxic compound, 2 high toxic compounds, 172 medium toxic compounds and 1518 low toxic compound.Conclusion QSAR model for prediction study on acute toxicity of chemical components of Chinese mareria medica can provide references combination medication and experimental studies.
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In order to provide a new way and method for safety evaluation of Chinese materia medica (CMM) and also to provide a reference for conventional animal experiments, computer toxicity prediction technique and method were established to predict the cardiotoxicity of CMM. Mold2 software (version 2.0.0) was used to calculate molecular descriptors of 1034 chemical components. Then, the random forest (RF) method and the support vector machine (SVM) method were used to screen the descriptors. After that, boosting trees method, SVM, regularized discriminant analysis method and RF method were used to build up prediction model, respectively. Finally, the cardiotoxicity of chemical components was predicted by the quantitative structure-activity relationship (QSAR) model with the best accuracy and Kappa value. The results showed that by comparing the accuracy and Kappa value of prediction model, it was found that the RF model was the optimal algorithm model with 86.3%accuracy and the Kappa value of 0. 725. Through the prediction research on chemical components of Chinese herbs with toxicity recorded in the Pharmacopoeia of People’s Republic of China (version2010),suchasEvodia rutaecarpa,North bean root,Murraya incense,some meaningful results had been received. It was concluded that QSAR model on prediction research of chemical components of Chinese herbs provided important references for further experimental studies and clinical researches.
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Studies on mechanisms of antimalarial action of artemisinin and its derivatives had been reviewed after artemisinin as an antimalarial drug was developed in 1972. The research work, which was mainly done by Chinese scholars, was introduced in the paper, and comprised 4 aspects:histopathology on the ultrastructure by electro-microscopy, the metabolism including the pigment clumping of the malarial parasite by biochemical pharmacology, and oxidation and Fe iron’s effect that were discussed in details based on studies from both domestic and international labs.
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The aim of this study is to explore the tissue distribution of PEGylated puerarin in acute myocardial ischemia model rats. Healthy male SD rats were randomly divided into two groups (30 each). Both were given PEGylated puerarin at a dose of 488 mg x kg(-1). After 5 min of medication, one group was normal rats, another group with acute myocardial ischemia was established by peritoneal injection of 50 mg x kg(-1) isoprenaline. After administration, the animals were executed at 30, 60, 90, 120, 150 and 180 min, then heart, liver, spleen, lung, kidney were extracted. The content of puerarin in organ tissue was determined by HPLC. The results showed that the AUC of tissue distribution of PEGylated puerarin in normal rats was liver > kidney > heart ≈ spleen > lung > brain. While the AUC of tissue distribution of PEGylated puerarin in acute myocardial ischemia model rats was liver ≈ heart > kidney > lung ≈ spleen > brain. AUC(heart) of PEGylated puerarin in acute myocardial ischemia model rats was 1.7 times than that of the normal rats, and there was significant difference (P < 0.05). Thus, PEGylated puerarin had a good heart-targeting property in early myocardial infarction area, drugs could accumulate in the ischemic myocardium. It provided important information for further study and clinic use of PEGylated puerarin.
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Objective To observe the antioxidative dosage-effect relationship of Marigold lutein, and provide experimental data for clinical use. Methods The mice were randomly divided into seven groups:blank control group, model control group, 1 mg/kg lutein group, 5 mg/kg lutein group, 25 mg/kg lutein group, 125 mg/kg lutein group and 625 mg/kg lutein group. The mice in blank control group were dealt with saline solution by intraperitoneal injection, the others were dealt with D-galactose (120 mg/kg) by intraperitoneal injection for seven weeks to make oxidative damage model, meanwhile the mice were given corresponding dose of the drug. Subsequently, the level of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) in the serum were measured, and the antioxidative dosage-effect relationship was observed. Results The 1, 5, 25 mg/kg lutein reduced the MDA level and increased SOD activity, and the 125, 625 mg/kg dose of lutein did not show significant antioxidant activity. Conclusion Lutein has significant antioxidant activity in mouse dealt with D-galactose within the dose range of 1-25 mg/kg. The results suggest that the clinical dosage range of lutein should be kept within reasonable limits.
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Objective The toxicological compatibility of Aconiti Carmichaeli Radix, as a toxic Chinese medicinal herb, combined with the other ingredients in Sini Decoction was investigated to elucidate the rationality of the combination of the ingredients in Sini Decoction from toxicological point of view. Methods Three kinds of experiments, acute toxicity in mice, heart toxicity in rats and aconitines level in water extract of Sini Decoction and its ingredients including Aconiti Carmichaeli Radix alone and its combination with licorice or dried ginger were adopted in this study. In the toxicological experiments, LD50 values for the acute toxicity test and TD50 values for the heart toxicity (arrhythemia as a parameter) of Sini Decoction, Aconiti Carmichaeli Radix alone and its combination with licorice or dried ginger were comparatively determined. And levels of individual aconitines of the water extracts from Sini Decoction, Aconiti Carmichaeli Radix alone and its combination with licorice or dried ginger were measured, respectively. Results The LD50 and TD50 of the combination of Aconiti Carmichaeli Radix and licorice in Sini Decoction were found to be higher than Aconiti Carmichaeli Radix alone or Sini Decoction, while the LD50 and TD50 of the combination of Aconiti Carmichaeli Radix and dried ginger appeared to be not different from those of Aconiti Carmichaeli Radix alone. The level of the main toxic compound of the water extracts for the combination of Aconiti Carmichaeli Radix and licorice, and Sini Decoction was lower than that of Aconiti Carmichaeli Radix alone and its combination with dried ginger. Conclusion The combination of Aconiti Carmichaeli Radix and licorice can attenuate the toxicity of Aconiti Carmichaeli Radix.
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<p><b>OBJECTIVE</b>To develop animal models and methodologies for assay of pseudoallergy induced by injectable drugs.</p><p><b>METHOD</b>Rats cutaneous anaphylactoid reaction model was developed by intravenous injection of 0. 6% Evans blue(EB) followed by intracutaneous injection of test substance solutions 50 microL. Diameters of subcutaneous blue spots and EB exudation were assayed.</p><p><b>RESULT</b>Rat anaphylactoid reaction was characterized as vascular hyperpermeability which was measured by diameters of blue spots inside the skin and the EB exudation of the blue spots. Compound 48/80 caused severe bluing and EB exudation in the skin by inducing obvious vascular hyperpermeability which indicated that it can induce rat skin pseudoallergy. Normal saline or 5% glucose injection showed no obvious reactions. The rat pseudoallergy model was validated by intracutaneous injections of western drug injections and Chinese medicine.</p><p><b>CONCLUSION</b>Rats could be developed into skin pseudoallergy model for preclinical safety evaluation of injectable drugs. The pseudoallergy reaction in this model is of high clinic consistency, sensitivity, reproducibility, and maneuverability. The model is suitable for the evaluation for pseudoallergy induced by injectable products prepared from Chinese materia medica This model can also be used for safety assay and quality control in manufacturing process, spot checking of marketed products, screening of allergen as well as studying of pseudoallergy mechanism.</p>
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Animales , Femenino , Masculino , Ratas , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Métodos , Hipersensibilidad a las Drogas , Inyecciones Subcutáneas , Métodos , Ratas Sprague-Dawley , PielRESUMEN
<p><b>OBJECTIVE</b>To develop animal models and methodologies for assay of pseudoallergy induced by injectable drugs.</p><p><b>METHOD</b>Mouse anaphylactoid reaction model was developed by intravenous injection of test substance solutions containing Evans blue (EB). Scores of ear blue staining and quantitation of ear EB exudation were the parameters for the pseudoallergy reaction.</p><p><b>RESULT</b>Mouse anaphylactoid reaction was characterized as vascular hyperpermeability which was detectable in ears by quantitation of blue staining score and EB exudation. Compound 48/80 and histamine caused severe ear bluing and EB exudation by inducing obvious vascular hyperpermeability which indicated that they can induce mouse pseudoallergy. Intravenous injection of either normal saline or 5% glucose injection showed no ear bluing. The mouse pseudoallergy model was validated by intravenous injections of western drugs and Chinese medicine.</p><p><b>CONCLUSION</b>Mice could be developed into pseudoallergy model for preclinical safety evaluation of injectable drugs. The pseudoallergy reaction in this model is of high clinic consistency, sensitivity, reproducibility, and maneuverability. The model is suitable for the evaluation for pseudoallergy induced by injectable products prepared from Chinese materia medica This model can also be used for safety assay and quality control in manufacturing process, spot checking of marketed products, screening of allergen as well as studying of pseudoallergy mechanism.</p>
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Animales , Ratones , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Métodos , Hipersensibilidad a las Drogas , Inyecciones Intravenosas , Ratones Endogámicos ICRRESUMEN
<p><b>OBJECTIVE</b>According to the record of mutual-detoxication and mutual restraint in ancient Chinese materia medica, to research the influence to the toxicity of Aconiti Carmichaeli Radix added the traditional Chinese medicine (TCM) which is mutual-detoxication and mutual restraint to it.</p><p><b>METHOD</b>ICR mouse, 0.4 microL x g(-1), to pour the fluid into stomach, paired comparison of acute toxicity of Aconiti Carmichaeli Radix seperately added different ratio of Sileris Radix, Astragali Radix and Polygalae Radix, and ad-measure the dose for LD50. SD rats, administration by injection through duodenum, 20 microL x g(-1), paired comparison of heart toxicity of Aconiti Carmichaeli Radix seperately added different ratio of Sileris Radix, Astragali Radix and Polygalae Radix, and admeasure the dose for TD50.</p><p><b>RESULT</b>LD50, and heart toxicity of TD50 were increased after Aconiti Carmichaeli Radix added separately, its toxicity attenuation is related to the ratio.</p><p><b>CONCLUSION</b>Mutual-detoxication and mutual restraint are the summary drawed when China ancient people is in the process of using toxic TCM and it is scientific.</p>
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Animales , Femenino , Masculino , Ratones , Ratas , Aconitum , Química , Planta del Astrágalo , Química , Composición de Medicamentos , Interacciones Farmacológicas , Medicamentos Herbarios Chinos , Farmacocinética , Toxicidad , Corazón , Inactivación Metabólica , Ratones Endogámicos ICR , Polygala , Química , Ratas Sprague-DawleyRESUMEN
<p><b>OBJECTIVE</b>Through the paired comparison on the toxicity effect of Aconiti Lateralis Radix Praeparata of different compatibility proportion of Aconiti Lateralis Radix Praeparata and Glycyrrhizae Radix et Rhizoma, to observe the detoxication effect of Glycyrrhizae Radix et Rhizoma to Aconiti Lateralis Radix Praeparata.</p><p><b>METHOD</b>Paired comparison on the mouse acute toxicity of Aconiti Lateralis Radix Praeparata and Aconiti Lateralis Radix Praeparata with different compatibility proportion of Glycyrrhizae Radix et Rhizoma, to assay the LD50. Paired comparison on the rat heart toxicity of Aconiti Lateralis Radix Praeparata and Aconiti Lateralis Radix Praeparata with different compatibility proportion of Glycyrrhizae Radix et Rhizoma, to assay the TD50. We dilute medicated serum of Aconiti Lateralis Radix Praeparata, Aconiti Lateralis Radix Praeparata plus Glycyrrhizae Radix et Rhizoma (3:1), Aconiti Lateralis Radix Praeparata plus Glycyrrhizae Radix et Rhizoma (1: 1) into 5%, 10%, 20% solution with serum free DMEM, to survey the effect of different concentration of medicated serum to the pulsing rhythm of myocardial cell of original generation newborn rat, cell surviva rate and content of LDH in myocardial cells.</p><p><b>RESULT</b>LD50 and TD50 of Aconiti Lateralis Radix Praeparata can be increased after adding Glycyrrhizae Radix et Rhizoma Compared to the blank serum, medicated serum with Aconiti Lateralis Radix Praeparata can obviously increased the pulse rhythm of myocardial cell and the content of LDH (P < 0.05). The medicated serum with Aconiti Lateralis Radix Praeparata added different proportion of Glycyrrhizae Radix et Rhizoma can reduce the acceleration of myocardial cell's rhythm, which is induced by Aconiti Lateralis Radix Praeparata, and can reduce the content of LDH. With the increased ratio of Glycyrrhizae Radix et Rhizoma, the effect is stronger. But for the serum with different concerntration of Aconiti Lateralis Radix Praeparata or Aconiti Lateralis Radix Praeparata added Glycyrrhizae Radix et Rhizoma, there is no obvious effect to the cell survival.</p><p><b>CONCLUSION</b>Glycyrrhizae Radix et Rhizoma has the detoxication effect through increasing the ultimatetotaldosage of Aconiti Lateralis Radix Praeparata. The detoxication effect of Glycyrrhizae Radix et Rhizoma to Aconiti Lateralis Radix Praeparata is through restraining the increased rhythm of myocardial cell and protecting the myocardial cell.</p>
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Animales , Femenino , Masculino , Ratones , Ratas , Aconitum , Química , Células Cultivadas , Química Farmacéutica , Métodos , Interacciones Farmacológicas , Medicamentos Herbarios Chinos , Farmacocinética , Toxicidad , Glycyrrhiza , Química , Inactivación Metabólica , Ratones Endogámicos ICR , Miocitos Cardíacos , Metabolismo , Ratas Sprague-Dawley , Rizoma , QuímicaRESUMEN
The primary objective was to develope a UPLC method for determine the concentration of buspirone hydroxychloride in plasma and to evaluate the effects of Aconiti Laterlis Radix and Aconiti Laterlis Radix compatibility of Glycyrrhizae Radix on CYP3A4 in vivo. ACQUITY UPLC BEH C18 column (2.1 mm x 10 mm, 1.7 microm) was used for the gradient elution with a 2.0 mmol x L(-1) ammonium acetate (pH 7.4, A)-acetonitrile (B) solution, 0-2.2 min, 10% - 60% B, 2.2-2.5 min, 60% B, 2.5-3.0 min, 60%-75% B, 3.0-3.5 min, 75% B, 3.5-4.0 min, 75%-10% B, at the flow rate of 0.3 mL x min(-1) at room temperature. The UV wavelenght was detected at 243 nm. The linear calibration curve ranged between 0.078 125-20.0 microg (r = 0.9975). The average recovery (n = 6) of buspirone hydroxychloride was 85.62% (RSD 6.8%). The results showed that this method has good specificity and repeatability, and which can be used for the determination of buspirone hydrochlorid in serum. In animial studies, single dose Aconiti Laterlis Radix extract treatment (0.5 g x kg(-1)) decreased buspirone hydroxychloride AUC(0-2 h) (52.8%, P = 0.020), increased CL/F (122%, P = 0.045). Compared to the saline treatment group, Aconiti Laterlis Radix compatibility of Glycyrrhizae Radix extract treatment has no effect on CYP3A4 in rat. The results indicated that Aconiti Laterlis Radix extract induced CYP3A4 while Aconiti Laterlis Radix compatibility of Glycyrrhizae Radix extract had no effect on CYP3A4 in vivo. Aconiti Laterlis Radix had been detoxified when be used as compatibility of Glycyrrhizae Radix.
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Animales , Masculino , Ratas , Aconitum , Química , Cromatografía Líquida de Alta Presión , Métodos , Citocromo P-450 CYP3A , Sistema Enzimático del Citocromo P-450 , Genética , Metabolismo , Medicamentos Herbarios Chinos , Expresión Génica , Glycyrrhiza , Química , Interacciones de Hierba-Droga , Ratas Sprague-DawleyRESUMEN
Toxic classification of traditional Chinese medicine, as a contribution of traditional Chinese medicine (TCM) to the recognition of medicinal toxicity and rational use of medicinal materials by Chinese people, is now a great issue related to safe medication, sustainable development and internationalization of Chinese medicine. In this article, the origination and development of toxic classification theory was summarized and analyzed. Because toxic classification is an urgent issue related to TCM industrialization, modernization and internationalization, this article made a systematic analysis on the nature and connotation of toxic classification as well as risk control for TCM industry due to the medicinal toxicity. Based on the toxic studies, this article made some recommendations on toxic classification of Chinese medicinal materials for the revision of China Pharmacopeia (volume 1). From the aspect of scientific research, a new technical guideline for research on toxic classification of Chinese medicine should be formulated based on new biological toxicity test technology such as Microtox and ADME/Tox, because the present classification of acute toxicity of mice/rats can not met the modern development of Chinese medicine any more. The evaluation system and technical SOP of TCM toxic classification should also be established, and they should well balance TCM features, superiority and international requirements. From the aspect of medicine management, list of toxic medicines and their risk classification should be further improved by competent government according to scientific research. In China Pharmacopeia (volume I), such descriptions of strong toxicity, toxicity or mild toxicity should be abandoned when describing medicine nature and flavor. This revision might help promote TCM sustainable development and internationalization, and enhance the competitive capacity of Chinese medicine in both domestic and international market. However, description of strong toxicity, toxicity or mild toxicity might be used when making cautions for the medicine, stating that the description is based on Chinese classic works. In this way, TCM traditional theory might be inherited and features of Chinese medicine maintained and reflected. Besides, modern findings should be added to the cautions, including dose-response relationship, toxic mechanism, and toxic elements. The traditional toxic descriptions and modern findings, as a whole, can make the caution clear and scientific, and then promote safe medication and TCM modernization and internationalization.
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Animales , Humanos , Ratones , Ratas , China , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Historia , Medicamentos Herbarios Chinos , Clasificación , Historia , Toxicidad , Historia Antigua , Medicina Tradicional China , Historia , Farmacología , HistoriaRESUMEN
This article discusses the characteristics of cmmunity herbal monographs for traditional herbal medicinal products and its establishment procedure. It also reviews the new development of cmmunity traditional herbal monographs. The purpose is to clarify the relationship between cmmunity herbal monographs and simplified registration for traditional herbal medicinal product in European Union and provide reference to the registration of taditional Chinese mdicinal products in Europe.
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Humanos , Aprobación de Drogas , Unión Europea , Fitoterapia , Plantas MedicinalesRESUMEN
To establish a HPLC method for the determination of vaccarin in Vaccariae Semen. Analysis was carried out on an Alltima-C18 column (4.6 mm x 250 mm, 5 microm) eluted with methanol -0.3% phosphoric acid as mobile phase in gradient elution. The flow rate was 1.0 mL x min(-1) and detected wavelength was set at 280 nm. The peak areas and injection ammounts of vaccarin showed a good linear relationship in the range of 0.102-1.539 microg, R2 = 0.9997. The average recovery was 100.4%, RSD was 0.81%. The results of the assay of 10 samples showed that the contents of vaccarin varied in the range of 0.46%-0.57%. The method is simple, accurate, reproducible and specific. It can be used for the quality control of Vaccariae Semen.
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Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos , Reproducibilidad de los Resultados , Vaccaria , QuímicaRESUMEN
<p><b>OBJECTIVE</b>To observe the effects of compound red yeast rice extract (CRYRE) on blood lipids, hemorheology and blood coagulant system in rats with hyperlipidemia.</p><p><b>METHOD</b>SD rats were randomly divided into six groups: normal control group, model group, Xuezhikang group (0. 24 g x kg(-1)), CRYRE high dose group (2.4 g x kg(-1)), middle dose group (1.2 g x kg(-1)) and low dose group (0.6 g x kg(-1)). The normal control rats were given pure water, and rats of other five groups were given 10 mL kg lipid emulsion and subjected to daily intragastric administration simultaneously in two days, continuously for 3 weeks. After the last medication, all the rats were sacrificed for measurement of blood lipids, hemorheology and coagulation factors.</p><p><b>RESULT</b>CRYRE 2.4 g x kg(-1) could significantly reduce the serum TG, TC levels and increase the HDL-C level (P < 0.01, P < 0.05). CRYRE 0.6-2.4 g x kg(-1) could significantly increase the ratios of HDL-C/TG,HDL-C/TC and HDL-C/LDL-C (P < 0.01). CRYRE 2.4 g x kg(-1) also reduced whole blood viscosity and plasma viscosity (P < 0.01, P < 0.05), prolonged active partial thromboplastin time, and lowered fibrinogen content (P < 0.01, P < 0.05).</p><p><b>CONCLUSION</b>CRYRE 2.4 g x kg(-1) could reduce blood lipids, blood viscosity and fibrinogen content, improve blood circulation, and depress the alteration of blood coagulant system resulted from lipid metabolic disorder in rats with hyperlipidemia.</p>
Asunto(s)
Animales , Humanos , Masculino , Ratas , Productos Biológicos , Química , Circulación Sanguínea , Modelos Animales de Enfermedad , Hiperlipidemias , Sangre , Quimioterapia , Hipolipemiantes , Química , Lípidos , Sangre , Distribución Aleatoria , Ratas Sprague-DawleyRESUMEN
<p><b>OBJECTIVE</b>To investigate the characteristics of embryonic toxicity of Senecio scandens, its total alkaloid and Qianbai Biyanpian so that to provide guidance for the safety of medication during pregnancy.</p><p><b>METHOD</b>Two hundred and twenty pregnant SD rats were divided into 11 groups: control group, positive group (cyclophosphamide 10 mg x kg(-1)). Water extract of S. scandens (doses: 7.5, 15.0, 30.0 g herb of S. scandens per kilogram body weight respectively). Qianbai Biyanpian and total alkaloid at the same doses levels with the water extract of S. scandens (doses were expressed as herb of S. scandens per kilogram body weight). The test articles were given to the pregnant rats by gavage from day 6 to day 15 of pregnancy. Body weight and the food consumption of pregnancy rats, and fetal weight and length were measured. The number of absorbed and dead embryos was recorded. Fetuses were examined in viscus and bones.</p><p><b>RESULT</b>Weight and the food consumption of pregnancy rats in high-dose of Qianbai Biyanpian and total alkaloids decreased. All treatment groups had no significant change in the number of absorbed embryos, but the stillbirths were significantly increased in high-dose groups of water extract and total alkaloids as compared with control group. Bone deformities such as fontanel expanding, hypoplasia of parietal bone, occipital bone and cervical arch were observed. Rib abnormality could also be seen in some rats. All water extract of S. scandens, Qianbai Biyanpian and total alkaloid could cause the bone abnormalities, but the percentage of bone deformities of total alkaloids was the highest (up to 80%).</p><p><b>CONCLUSION</b>S. scandens and its total alkaloids, its formula Qianbai Biyanpian can cause rat skeletal deformities in fetuses when they were given during pregnancy. It is suggested that S. scandens and the product containing S. scandens should not be used during pregnancy.</p>