Objective The effects of Shuang Dan Ming Mu capsule on expression of VEGF-a,VEGF-b,VEGF-c and the VEGF receptor,Flk-1,were examined in a diabetic retinopathy rats model.Methods Forty Sprague-Dawley(SD)rats were random...Objective The effects of Shuang Dan Ming Mu capsule on expression of VEGF-a,VEGF-b,VEGF-c and the VEGF receptor,Flk-1,were examined in a diabetic retinopathy rats model.Methods Forty Sprague-Dawley(SD)rats were randomized into Groups A(blank),B(model),C(Shuang Dan Ming Mu)and D(positive control)group,with each group containing10rats and20eyes.Rats from groups B,C and D were administered one dose of50mg/kg streptozotocin(STZ)by tail vein injection to establish a diabetic rat model.One week after model preparation,medication was continuously administered by gavage.After gavage for8weeks,the animals were sacrificed and retinal expression of VEGF-a,VEGF-b,VEGF-c and Flk-1was quantified by immunohistochemical analysis.Results At week8of drug administration after model preparation,the average protein expression grayscale values for VEGF-a,VEGF-b,VEGF-c and Flk-1in the rats model,Shuang Dan Ming Mu and positive control groups were all lower than those in the normal group,while the mean optical density values were higher than those in the normal group.When the model group was compared to the normal group,the difference was extremely significant(P<0.01).The mean grayscale values of VEGF-a,VEGF-b,VEGF-c and Flk-1in the Shuang Dan Ming Mu and positive control groups were all higher than those in the model group,while the mean optical density values were lower than those in the model group(P<0.05or0.01).Conclusion Shuang Dan Ming Mu capsule can significantly decrease the expression of VEGF-a,VEGF-b,VEGF-c and Flk-1in the retinas of diabetic model rats and exhibit some protective effects in their retinas.展开更多
OBJECTIVE:To characterize naringenin(NAR) population pharmacokinetics(PPK) in Chinese women with primary osteoporosis.METHODS:Ninety-eight female patients with primary osteoporosis from the Jingshan,Beixinqiao,Jiaodao...OBJECTIVE:To characterize naringenin(NAR) population pharmacokinetics(PPK) in Chinese women with primary osteoporosis.METHODS:Ninety-eight female patients with primary osteoporosis from the Jingshan,Beixinqiao,Jiaodaokou,Chaoyangmen,and Donghuamen communities in Beijing,China,aged 40 to 80 years,received oral Qianggu capsules(250 mg).Blood samples were collected before and at 0.5,1,2,3,4,6,8,10,12,and 24 h after administration.The concentration of NAR in the blood samples was measured using high performance liquid chromatography-tandem mass spectrometry.PPK analyses were performed with nonlinear mixed-effect modeling software(version 7.1.2,PsN3.2.12).The clearance(C1),central distribution volume(V),absorption rate constant(Ka1),peripheral distribution volume(VII),and inter-compartmental clearance(CLII) were set as parameters and estimated by the base model,covariate model,and final model.Kidney-Yang deficiency[Shenyangxu(SYAX)]and liver-kidney-Yin deficiency(Ganshenyinxu) are patterns of symptoms in Traditional Chinese Medicine that were set as covariates,along with age,height,blood urea nitrogen,serum creatinine,alanine transaminase,aspartate transaminase,and hyperlipidemia.Both stepwise forward and backward procedures were accomplished to build models.The final model was evaluated by internal and external validation,visual predictive check,bootstrap,and leverage analysis.RESULTS:A one compartment open model with first order degradation was the best fitted to the concentration-time profiles following oral administration of NAR.The mean of population parameters of the final model,C1,SYAX on C1,V,Ka1,CLII,and VII,were measured to be 37.6 L/h,0.427 L,123 L/h,0.12/h,0.3056,and 1.446,respectively.Inter-individual variability was estimated and SYAX was identified as a significant covariate.CONCLUSION:The population pharmacokinetic model described in this study could effectively characterize the pharmacokinetic profile of NAR following administration of a single dose of oral Qianggu capsules in Chinese women with primary osteoporosis.Among the tested covariates,only SYAX was a significant factor.展开更多
OBjECTIVE:To observe the relationship between reduced pulmonary function and regulatory T cells(Tregs)and helper T cells(Th)1/Th2 drift in a rat model of adjuvant arthritis(AA),and to study the impact of Xinfeng capsu...OBjECTIVE:To observe the relationship between reduced pulmonary function and regulatory T cells(Tregs)and helper T cells(Th)1/Th2 drift in a rat model of adjuvant arthritis(AA),and to study the impact of Xinfeng capsule(XFC)on pulmonary function and investigate the mechanism of action.METHODS:Forty rats were randomly divided into normal control group(NC),model control group(MC),Tripterygium glycosides tablet group(TPT),and XFC group,with 10 in each.Except for the NCgroup,AA was induced in all rats by intracutaneous injection of 0.1 mL Freund's complete adjuvant in the right paw.On the 19th day after modeling,the NC and MC groups were given physiological saline(0.9%),while the TPT and XFC groups were given TPT(10 mg/kg)and XFC(2.4 g/kg),once daily,respectively.Thirty days after administration,changes in paw swelling,arthritis index(AI),pulmonary function,levels of serumγ-interferon(IFN-γ)and interleukin(IL)-4,Tregs in peripheral blood,and IFN-γ,IL-4,Forkhead box transcription factor 3(FoxP3)in lung tissue were observed by enzyme-linked immunosorbent assay,flow cytometry,polymerase chain reaction,and western blot.RESULTS:Compared with the NC group,paw swelling,AI,IFN-γ,and Th1/Th2 were increased,and pulmonary function parameters,IL-4,FoxP3 were decreased significantly in the MC group(P<0.05 or P<0.01).Pulmonary function parameters,Treg,IL-4,FoxP3(and mRNA)were higher,and paw swelling,AI,and IFN-γ(and mRNA)were lower in the XFC group than those in the MC group.The XFC group was also much better than theTPT group in improving pulmonary function,FoxP3 mRNA,IFN-γ,IL-4,Th1/Th2,and IL-10(P<0.05 or P<0.01).CONCLUSION:Xinfeng capsule can improve pulmonary function by regulating the levels of Tregs,inhibiting the activation of Th1 to Th2 cells,inducing drift,maintaining cell immune suppression,correcting the imbalance of Th1/Th2,and reducing inflammatory mediators.展开更多
OBJECTIVE: To investigate the effects of Yindanxinnaotong capsule(YDXNTC) and main components compatibility and ratios on myocardium against ischemia/reperfusion injury and the effect's underlying mechanism.METHOD...OBJECTIVE: To investigate the effects of Yindanxinnaotong capsule(YDXNTC) and main components compatibility and ratios on myocardium against ischemia/reperfusion injury and the effect's underlying mechanism.METHODS: Myocardial ischemia/reperfusion injury(MIRI) was induced by ischemia for 30 min and reperfusion for 30 min. Electrocardiogram data and coronary flow were recorded, and superoxide dismutase(SOD), malondialdehyde(MDA), lactate dehydrogenase, creatine kinase-MB, cardiac troponin T and I(cT nT, cT n I) and interleukin-1β, interleukin-8,interleukin-18(IL-1β, IL-8, IL-18) in myocardium were measured. Hypoxia/reoxygenation and hydrogen peroxide(H2O2) injury were induced by hypoxia for 3 h/reoxygenation for 2 h, and 100 μM H2O2 for 1 h, respectively, in vitro rat myocardial cells(H9c2). Cell viability, SOD, MDA, cT nT and inflamma-tory factors(IL-1β, IL-8 and IL-18) were determined,and Toll-like receptor 4(TLR-4) expression was measured by western blotting.RESULTS: In the isolated heart experiment, elevated heart function, coronary flow and SOD levels,and decreased MDA levels and inflammatory factors were noted in the YDXNTC, main components and main components compatibility groups. Ventricular tachycardia/ventricular fibrillation occurrence decreased in the ginkgo biloba extract(GBE),and GBE and salvia miltiorrhiza ethanol extract compatibility(SM-E, GSEC) groups. Lactic dehydrogenase levels decreased in the YDXNTC and aqueous extract of salvia miltiorrhiza(SM-H) groups. Creatine kinase-MB decreased with GBE, SM-E, SM-H and GSEC treatment, and cT n I and cT nT levels decreased with GSEC. In the in vitro cell study,YDXNTC and main components ratios improved cell viability and SOD levels, and suppressed MDA,cT nT and inflammatory factors. TLR-4 expression was down-regulated.CONCLUSION: YDXNTC and main components compatibility showed protective effects on MIRI in this rat model and in vitro study. Regulating the Toll-like receptor signaling pathway may affect the mechanism.展开更多
基金funding support from the National Natural Science Foundation General Program (No. 814737370)Hunan Province Graduate Student Research Innovation Program (No. CX2016B377 and No. CX2017B432)+4 种基金Traditional Chinese Medicine Prevention and Treatment of Facial Feature Disease Hunan Province Key Laboratory Construction Program (No. 2017TP1018)Changsha City Science and Technology Program (No. kc1704005)Central Finance Supported Local High School Construction ProjectState Administration of Traditional Chinese Medicine Ophthalmology Key Discipline Construction ProjectHunan Province Traditional Chinese Medicine Facial Feature Key Discipline Construction Project
文摘Objective The effects of Shuang Dan Ming Mu capsule on expression of VEGF-a,VEGF-b,VEGF-c and the VEGF receptor,Flk-1,were examined in a diabetic retinopathy rats model.Methods Forty Sprague-Dawley(SD)rats were randomized into Groups A(blank),B(model),C(Shuang Dan Ming Mu)and D(positive control)group,with each group containing10rats and20eyes.Rats from groups B,C and D were administered one dose of50mg/kg streptozotocin(STZ)by tail vein injection to establish a diabetic rat model.One week after model preparation,medication was continuously administered by gavage.After gavage for8weeks,the animals were sacrificed and retinal expression of VEGF-a,VEGF-b,VEGF-c and Flk-1was quantified by immunohistochemical analysis.Results At week8of drug administration after model preparation,the average protein expression grayscale values for VEGF-a,VEGF-b,VEGF-c and Flk-1in the rats model,Shuang Dan Ming Mu and positive control groups were all lower than those in the normal group,while the mean optical density values were higher than those in the normal group.When the model group was compared to the normal group,the difference was extremely significant(P<0.01).The mean grayscale values of VEGF-a,VEGF-b,VEGF-c and Flk-1in the Shuang Dan Ming Mu and positive control groups were all higher than those in the model group,while the mean optical density values were lower than those in the model group(P<0.05or0.01).Conclusion Shuang Dan Ming Mu capsule can significantly decrease the expression of VEGF-a,VEGF-b,VEGF-c and Flk-1in the retinas of diabetic model rats and exhibit some protective effects in their retinas.
基金Supported by Grant from Significant Drug Research and Development in Important State Science and Technology Specific And Key Technique Research(Key Issues Research on Re-evaluation of Listed Herbal Hedicine,No.2009ZX09502-030)Visiting Fellow Joint Innovation Research Project of The China Academy of Chinese Medical Sciences(Exploratory Research in Population Pharmacokinetics of Bioactive Compounds of Osteopractic Total Flavone Based on Total Quantum Statistical Moment.No.ZZ070834)
文摘OBJECTIVE:To characterize naringenin(NAR) population pharmacokinetics(PPK) in Chinese women with primary osteoporosis.METHODS:Ninety-eight female patients with primary osteoporosis from the Jingshan,Beixinqiao,Jiaodaokou,Chaoyangmen,and Donghuamen communities in Beijing,China,aged 40 to 80 years,received oral Qianggu capsules(250 mg).Blood samples were collected before and at 0.5,1,2,3,4,6,8,10,12,and 24 h after administration.The concentration of NAR in the blood samples was measured using high performance liquid chromatography-tandem mass spectrometry.PPK analyses were performed with nonlinear mixed-effect modeling software(version 7.1.2,PsN3.2.12).The clearance(C1),central distribution volume(V),absorption rate constant(Ka1),peripheral distribution volume(VII),and inter-compartmental clearance(CLII) were set as parameters and estimated by the base model,covariate model,and final model.Kidney-Yang deficiency[Shenyangxu(SYAX)]and liver-kidney-Yin deficiency(Ganshenyinxu) are patterns of symptoms in Traditional Chinese Medicine that were set as covariates,along with age,height,blood urea nitrogen,serum creatinine,alanine transaminase,aspartate transaminase,and hyperlipidemia.Both stepwise forward and backward procedures were accomplished to build models.The final model was evaluated by internal and external validation,visual predictive check,bootstrap,and leverage analysis.RESULTS:A one compartment open model with first order degradation was the best fitted to the concentration-time profiles following oral administration of NAR.The mean of population parameters of the final model,C1,SYAX on C1,V,Ka1,CLII,and VII,were measured to be 37.6 L/h,0.427 L,123 L/h,0.12/h,0.3056,and 1.446,respectively.Inter-individual variability was estimated and SYAX was identified as a significant covariate.CONCLUSION:The population pharmacokinetic model described in this study could effectively characterize the pharmacokinetic profile of NAR following administration of a single dose of oral Qianggu capsules in Chinese women with primary osteoporosis.Among the tested covariates,only SYAX was a significant factor.
基金Supported by the National Natural Science Foundation Project(No.81173211)Medical Key Subjects Chinese Paraly-sis Disease in the National School Construction Projects[Tra-ditional Chinese Medicine(2009)No.30]+3 种基金Anhui Science and Technology Office of Scientific Research Program(09020304046)Anhui Provincial Health Department of Tra-ditional Chinese Medicine Research Projects(No.2009-ZY05)Anhui Modern Chinese Medicine Basic and Applied Research and Development Projects Provincial Laboratory(2008 No.150)Anhui Medical and Technological Innovation Team project(No.2010TD005)
文摘OBjECTIVE:To observe the relationship between reduced pulmonary function and regulatory T cells(Tregs)and helper T cells(Th)1/Th2 drift in a rat model of adjuvant arthritis(AA),and to study the impact of Xinfeng capsule(XFC)on pulmonary function and investigate the mechanism of action.METHODS:Forty rats were randomly divided into normal control group(NC),model control group(MC),Tripterygium glycosides tablet group(TPT),and XFC group,with 10 in each.Except for the NCgroup,AA was induced in all rats by intracutaneous injection of 0.1 mL Freund's complete adjuvant in the right paw.On the 19th day after modeling,the NC and MC groups were given physiological saline(0.9%),while the TPT and XFC groups were given TPT(10 mg/kg)and XFC(2.4 g/kg),once daily,respectively.Thirty days after administration,changes in paw swelling,arthritis index(AI),pulmonary function,levels of serumγ-interferon(IFN-γ)and interleukin(IL)-4,Tregs in peripheral blood,and IFN-γ,IL-4,Forkhead box transcription factor 3(FoxP3)in lung tissue were observed by enzyme-linked immunosorbent assay,flow cytometry,polymerase chain reaction,and western blot.RESULTS:Compared with the NC group,paw swelling,AI,IFN-γ,and Th1/Th2 were increased,and pulmonary function parameters,IL-4,FoxP3 were decreased significantly in the MC group(P<0.05 or P<0.01).Pulmonary function parameters,Treg,IL-4,FoxP3(and mRNA)were higher,and paw swelling,AI,and IFN-γ(and mRNA)were lower in the XFC group than those in the MC group.The XFC group was also much better than theTPT group in improving pulmonary function,FoxP3 mRNA,IFN-γ,IL-4,Th1/Th2,and IL-10(P<0.05 or P<0.01).CONCLUSION:Xinfeng capsule can improve pulmonary function by regulating the levels of Tregs,inhibiting the activation of Th1 to Th2 cells,inducing drift,maintaining cell immune suppression,correcting the imbalance of Th1/Th2,and reducing inflammatory mediators.
基金the Major National Science and Technology Projects:the Technology Reformation of Yindanxinnaotong Capsule(No.2012ZX09201201)
文摘OBJECTIVE: To investigate the effects of Yindanxinnaotong capsule(YDXNTC) and main components compatibility and ratios on myocardium against ischemia/reperfusion injury and the effect's underlying mechanism.METHODS: Myocardial ischemia/reperfusion injury(MIRI) was induced by ischemia for 30 min and reperfusion for 30 min. Electrocardiogram data and coronary flow were recorded, and superoxide dismutase(SOD), malondialdehyde(MDA), lactate dehydrogenase, creatine kinase-MB, cardiac troponin T and I(cT nT, cT n I) and interleukin-1β, interleukin-8,interleukin-18(IL-1β, IL-8, IL-18) in myocardium were measured. Hypoxia/reoxygenation and hydrogen peroxide(H2O2) injury were induced by hypoxia for 3 h/reoxygenation for 2 h, and 100 μM H2O2 for 1 h, respectively, in vitro rat myocardial cells(H9c2). Cell viability, SOD, MDA, cT nT and inflamma-tory factors(IL-1β, IL-8 and IL-18) were determined,and Toll-like receptor 4(TLR-4) expression was measured by western blotting.RESULTS: In the isolated heart experiment, elevated heart function, coronary flow and SOD levels,and decreased MDA levels and inflammatory factors were noted in the YDXNTC, main components and main components compatibility groups. Ventricular tachycardia/ventricular fibrillation occurrence decreased in the ginkgo biloba extract(GBE),and GBE and salvia miltiorrhiza ethanol extract compatibility(SM-E, GSEC) groups. Lactic dehydrogenase levels decreased in the YDXNTC and aqueous extract of salvia miltiorrhiza(SM-H) groups. Creatine kinase-MB decreased with GBE, SM-E, SM-H and GSEC treatment, and cT n I and cT nT levels decreased with GSEC. In the in vitro cell study,YDXNTC and main components ratios improved cell viability and SOD levels, and suppressed MDA,cT nT and inflammatory factors. TLR-4 expression was down-regulated.CONCLUSION: YDXNTC and main components compatibility showed protective effects on MIRI in this rat model and in vitro study. Regulating the Toll-like receptor signaling pathway may affect the mechanism.
