Compound Formula Rehmannia has been shown to be clinically effective in treating Parkinson＇s disease and levodopa-induced dyskinesia; however, the mechanisms remain unclear. In this study, we established a model of P...Compound Formula Rehmannia has been shown to be clinically effective in treating Parkinson＇s disease and levodopa-induced dyskinesia; however, the mechanisms remain unclear. In this study, we established a model of Parkinson＇s disease dyskinesia in rats, and treated these animals with Compound Formula Rehmannia. Compound Formula Rehmannia inhibited the increase in mRNA expression of N-methyl-D-aspartate receptor subunits 1 and 2 and excitatory amino acid neurotransmitter genes, and it inhibited the reduction in expression of γ-aminobutyric acid receptor B1, an inhibitory amino acid neurotransmitter gene, in the corpus striatum. In addition, Compound Formula Rehmannia alleviated dyskinesia symptoms in the Parkinson＇s disease rats. These experimental findings indicate that Compound Formula Rehmannia alleviates levodopa-induced dyskinesia in Parkinson＇s disease by modulating neurotransmitter signaling in the corpus striatum.展开更多
The governing equation of the discharge per unit width, derived from the flow continuity equation and the momentum equation in the vegetated compound chan- nel, is established. The analytical solution to the discharge...The governing equation of the discharge per unit width, derived from the flow continuity equation and the momentum equation in the vegetated compound chan- nel, is established. The analytical solution to the discharge per unit width is presented, including the effects of bed friction, lateral momentum transfer, drag force, and secondary flows. A simple＇ but available numerical integral method, i.e., the compound trapezoidM formula, is used to calculate the approximate solutions of the sub-area discharge and the total discharge. A comparison with the published experimental data from the U. K. Flood Channel Facility （UK-FCF） demonstrates that this model is capable of predicting not only the stage-discharge curve but also the sub-area discharge in the vegetated com- pound channel. The effects of the two crucial parameters, i.e., the divided number of the integral interval and the secondary flow coefficient, on the total discharge are discussed and analyzed.展开更多
Long-term application of levodopa （L-3, 4-dihydroxyphenylalanine, L-DOPA） for Parkinson＇s disease can lead to adverse effects and reduce the amount of dopamine transporter （DAT） in the corpus striatum. The presen...Long-term application of levodopa （L-3, 4-dihydroxyphenylalanine, L-DOPA） for Parkinson＇s disease can lead to adverse effects and reduce the amount of dopamine transporter （DAT） in the corpus striatum. The present study attempted to vedfy whether increasing the amount of DAT can reduce the adverse effects of L-DOPA. The specific radioactive uptake value of DAT in the corpus striatum of the lesioned hemisphere was significantly decreased, but was significantly increased following administration of compound rehmannia formula [Radix rehmanniae preparata （prepared rehmannia root）, Concha margantifera usta （nacre）, Radix paeoniae alba （white peony alba）, Radix salviae miltiotThizae （Danshen root）, Scorpio （scorpion）, green tea] for 4 weeks. The changes in DAT 1251-beta-carbomethoxy-3 beta-（4-iodophenyl） tropane autoradiography were consistent with those in radioactivity. The results revealed that the compound rehmannia formula can reduce the adverse effects of L-DOPA in treating Parkinson＇s disease, possibly by increasing the amount of DAT.展开更多
Objective:To investigate the effect of Shenqi Compound Formula (SCF) on peroxisome proliferators-activated receptor γ (PPARγ) in white adipose tissue of rats with macrovascular lesion in early stage of diabetes. Met...Objective:To investigate the effect of Shenqi Compound Formula (SCF) on peroxisome proliferators-activated receptor γ (PPARγ) in white adipose tissue of rats with macrovascular lesion in early stage of diabetes. Methods: Corresponding treatment was given to rats in model group, Ramipril group, normal control group, low dosage SCF group and high dosage SCF group respectively for 32 days. The expressions of PPARγ and adiponectin Messenger RNA (mRNA) were detected by real-time reverse transcriptase poly-merase chain reaction. Results: The expressions of PPARγ and adiponectin mRNA increased significantly in both low and high dosage SCF groups as compared with the model group, and a positive linear correlation was found between the expressions of PPARγ and adiponectin mRNA. Conclusions: SCF can prevent macrovascular lesion in early stage of diabetes, which is possibly related with up-regulating expressions of PPARγ and activating PPARγ.展开更多
To evaluate the effect of components in Guanxin Ⅱ prescription on the pharmacokinetic profiles of paeoniflorin. Plasma concentration of Paeoniflorin in rats after intravenous injection of Paronia Pall Extract （PPE）...To evaluate the effect of components in Guanxin Ⅱ prescription on the pharmacokinetic profiles of paeoniflorin. Plasma concentration of Paeoniflorin in rats after intravenous injection of Paronia Pall Extract （PPE） and oral administration of PPE and three types of decoctions in Guanxin Ⅱ prescription, respectively, were determined by HPLC analyses. NONMEM （nonlinear mixed-effect modeling） method was used to analyze full set of pharmacokinetic data directly. A two-compartment model with first-order degradation in absorption compartment was employed for the data analysis. The mean of population parameters, CL1, V1, CL2, V2, Ka0, and Kal, were measured to be 0.509 L/h, 0.104 L, 0.113 L/h, 0.123 L, 0.135/h, and 0.0135/h, respectively. Inter-individual variabilities were estimated and dose formulation （DF） was identified as a significant covariate of Ka 1, Ka0, and V1. It is concluded that the pharmacokinetic behaviors of paeoniflorin in rats can alter with different dose formulations.展开更多
BACKGROUND Recent research suggests that although prokinetic agents,acid suppressors,and radical treatment for Helicobacter pylori infection may be effective in patients with functional dyspepsia(FD),a large proportio...BACKGROUND Recent research suggests that although prokinetic agents,acid suppressors,and radical treatment for Helicobacter pylori infection may be effective in patients with functional dyspepsia(FD),a large proportion of patients still fail to respond to these treatments or may suffer from severe adverse reactions.Many traditional Chinese medicinal herbs can regulate the status of the entire body and have special advantages in the treatment of functional diseases.The present study was designed to verify the efficacy of Biling Weitong Granules(BLWTG),a traditional Chinese medicinal herbal compound formula,in alleviating epigastric pain syndrome(EPS)in FD patients,in an attempt to provide an effective prescription for the clinical treatment of this disease.AIM To evaluate the clinical efficacy and safety of BLWTG in treating EPS in patients with FD.METHODS In this multicenter,stratified,randomized,double-blind,placebo-controlled,parallel group clinical trial,eligible patients were randomized into the BLWTG and placebo groups who were treated for 6 wk.Efficacy indicators including the severity and frequency of EPS and the time to pain resolution and safety indicators including adverse events were observed and compared.RESULTS The baseline demographic data and clinical characteristics,such as epigastric pain symptoms,pain intensity,and frequency of attacks,were matched between the two groups before randomization.After 6 wk of treatment and after the center effect was eliminated,the epigastric pain was significantly improved in 28.33%and 85.59%of the patients in the placebo and BLWTG groups,respectively(P<0.05).At 6 wk,the resolution rate of epigastric pain was 15%and 69.49%in the placebo and BLWTG groups,respectively(P<0.05).The differences of total FD clinical score between these two groups were significant(P<0.05)at 2,4,and 6 wk(P<0.05).The scores of each item and the total score in the Functional Digestive Disorders Quality of Life Questionnaire showed significant differences between the two groups at 6 wk after both the center and interaction effects were eliminated(P<0.05).There was no significant difference in the incidence of adverse events between the two groups,and no serious adverse event was noted during the observation.CONCLUSION Compared with placebo,BLWTG markedly improved EPS in FD patients without causing serious adverse reactions.展开更多
OBJECTIVE:To explore the mechanism of Dangua Fang(丹瓜方,DGR)in multi-target and multi-method regulation of glycolipid metabolism based on phosphoproteomics.METHODS:Sprague-Dawley rats with normal glucose levels were ...OBJECTIVE:To explore the mechanism of Dangua Fang(丹瓜方,DGR)in multi-target and multi-method regulation of glycolipid metabolism based on phosphoproteomics.METHODS:Sprague-Dawley rats with normal glucose levels were randomly divided into three groups,including a conventional diet control group(Group A),high-fat-highsugar diet model group(Group B),and DGR group(Group C,high-fat-high-sugar diet containing 20.5 g DGR).After 10 weeks of intervention,the fasting blood glucose(FBG),2 h blood glucose[PBG;using the oral glucose tolerance test(OGTT)],hemoglobin A1c(HbA1c),plasma total cholesterol(TC),and triglycerides(TG)were tested,and the livers of rats were removed to calculate the liver index.Then,hepatic portal TG were tested using the Gross permanent optimization-participatiory action planning enzymatic method and phosphoproteomics was performed using liquid chromatography with tandem mass spectrometry(LC-MS/MS)analysis followed by database search and bioinformatics analysis.Finally,cell experiments were used to verify the results of phosphoproteomics.Phosphorylated mitogen-activated protein kinase kinase kinase kinase 4(MAP4k4)and phosphorylated adducin 1(ADD1)were detected using western blotting.RESULTS:DGR effectively reduced PBG,TG,and the liver index(P<0.05),and significantly decreased HbA1c,TC,and hepatic portal TG(P<0.01),showed significant hematoxylin and eosin(HE)staining,red oil O staining,and Masson staining of liver tissue.The total spectrum was 805334,matched spectrum was 260471,accounting for accounting 32.3%,peptides were 19995,modified peptides were 14671,identified proteins were 4601,quantifiable proteins were 4417,identified sites were 15749,and quantified sites were 14659.Based on the threshold of expression fold change(>1.2),DGR upregulated the modification of 228 phosphorylation sites involving 204 corresponding function proteins,and downregulated the modification of 358 phosphorylation sites involving 358 corresponding function proteins,which included correcting 75 phosphorylation sites involving 64 corresponding function proteins relating to glycolipid metabolism.Therefore,DGR improved biological tissue processes,including information storage and processing,cellular processes and signaling,and metabolism.The metabolic functions regulated by DGR mainly include energy production and conversion,carbohydrate transport and metabolism,lipid transport and metabolism,inorganic ion transport and metabolism,secondary metabolite biosynthesis,transport,and catabolism.In vitro phosphorylation validation based on cell experiments showed that the change trends in the phosphorylation level of MAP4k4 and ADD1 were consistent with that of previous phosphoproteomics studies.CONCLUSION:DGR extensively corrects the modification of phosphorylation sites to improve corresponding glycolipid metabolism-related protein expression in rats with glycolipid metabolism disorders,thereby regulating glycolipid metabolism through a multi-target and multi-method process.展开更多
基金supported by the National Natural Science Foundation of China,No.30672684,30973722Science and Technology Support Traditional Chinese Drug Research and Development Project of Shanghai,No.F50102+1 种基金Traditional Chinese Medicine Research Fund of Shanghai Municipal Health Bureau,No.2012J009AAnnual Research Budget of Shanghai University of Traditional Chinese Medicine in 2013,No.2013JW25
文摘Compound Formula Rehmannia has been shown to be clinically effective in treating Parkinson＇s disease and levodopa-induced dyskinesia; however, the mechanisms remain unclear. In this study, we established a model of Parkinson＇s disease dyskinesia in rats, and treated these animals with Compound Formula Rehmannia. Compound Formula Rehmannia inhibited the increase in mRNA expression of N-methyl-D-aspartate receptor subunits 1 and 2 and excitatory amino acid neurotransmitter genes, and it inhibited the reduction in expression of γ-aminobutyric acid receptor B1, an inhibitory amino acid neurotransmitter gene, in the corpus striatum. In addition, Compound Formula Rehmannia alleviated dyskinesia symptoms in the Parkinson＇s disease rats. These experimental findings indicate that Compound Formula Rehmannia alleviates levodopa-induced dyskinesia in Parkinson＇s disease by modulating neurotransmitter signaling in the corpus striatum.
基金Project supported by the National Natural Science Foundation of China(Nos.51279117 and 11072161)the Program for New Century Excellent Talents in University of China(No.NCET-130393)the National Science and Technology Ministry of China(No.2012BAB05B02)
文摘The governing equation of the discharge per unit width, derived from the flow continuity equation and the momentum equation in the vegetated compound chan- nel, is established. The analytical solution to the discharge per unit width is presented, including the effects of bed friction, lateral momentum transfer, drag force, and secondary flows. A simple＇ but available numerical integral method, i.e., the compound trapezoidM formula, is used to calculate the approximate solutions of the sub-area discharge and the total discharge. A comparison with the published experimental data from the U. K. Flood Channel Facility （UK-FCF） demonstrates that this model is capable of predicting not only the stage-discharge curve but also the sub-area discharge in the vegetated com- pound channel. The effects of the two crucial parameters, i.e., the divided number of the integral interval and the secondary flow coefficient, on the total discharge are discussed and analyzed.
基金the National Natural Science Foundation of China,No.30672684, 30973722the Third Intention Key Disciplinary Areas of Shanghai,No.S30302
文摘Long-term application of levodopa （L-3, 4-dihydroxyphenylalanine, L-DOPA） for Parkinson＇s disease can lead to adverse effects and reduce the amount of dopamine transporter （DAT） in the corpus striatum. The present study attempted to vedfy whether increasing the amount of DAT can reduce the adverse effects of L-DOPA. The specific radioactive uptake value of DAT in the corpus striatum of the lesioned hemisphere was significantly decreased, but was significantly increased following administration of compound rehmannia formula [Radix rehmanniae preparata （prepared rehmannia root）, Concha margantifera usta （nacre）, Radix paeoniae alba （white peony alba）, Radix salviae miltiotThizae （Danshen root）, Scorpio （scorpion）, green tea] for 4 weeks. The changes in DAT 1251-beta-carbomethoxy-3 beta-（4-iodophenyl） tropane autoradiography were consistent with those in radioactivity. The results revealed that the compound rehmannia formula can reduce the adverse effects of L-DOPA in treating Parkinson＇s disease, possibly by increasing the amount of DAT.
文摘Objective:To investigate the effect of Shenqi Compound Formula (SCF) on peroxisome proliferators-activated receptor γ (PPARγ) in white adipose tissue of rats with macrovascular lesion in early stage of diabetes. Methods: Corresponding treatment was given to rats in model group, Ramipril group, normal control group, low dosage SCF group and high dosage SCF group respectively for 32 days. The expressions of PPARγ and adiponectin Messenger RNA (mRNA) were detected by real-time reverse transcriptase poly-merase chain reaction. Results: The expressions of PPARγ and adiponectin mRNA increased significantly in both low and high dosage SCF groups as compared with the model group, and a positive linear correlation was found between the expressions of PPARγ and adiponectin mRNA. Conclusions: SCF can prevent macrovascular lesion in early stage of diabetes, which is possibly related with up-regulating expressions of PPARγ and activating PPARγ.
基金National Natural Science Foundation (Grant No. 30472165)
文摘To evaluate the effect of components in Guanxin Ⅱ prescription on the pharmacokinetic profiles of paeoniflorin. Plasma concentration of Paeoniflorin in rats after intravenous injection of Paronia Pall Extract （PPE） and oral administration of PPE and three types of decoctions in Guanxin Ⅱ prescription, respectively, were determined by HPLC analyses. NONMEM （nonlinear mixed-effect modeling） method was used to analyze full set of pharmacokinetic data directly. A two-compartment model with first-order degradation in absorption compartment was employed for the data analysis. The mean of population parameters, CL1, V1, CL2, V2, Ka0, and Kal, were measured to be 0.509 L/h, 0.104 L, 0.113 L/h, 0.123 L, 0.135/h, and 0.0135/h, respectively. Inter-individual variabilities were estimated and dose formulation （DF） was identified as a significant covariate of Ka 1, Ka0, and V1. It is concluded that the pharmacokinetic behaviors of paeoniflorin in rats can alter with different dose formulations.
基金National New Drug Innovation Program,No.2017ZX09304003Special Research on Modernization of Traditional Chinese Medicine in the National Key Research and Development Program in the 13th Five-Year Plan Demonstrative Research,No.2017YFC1703703.Institutional review board statement:This study was approved by the IRB of Xiyuan Hospital of China Academy of Chinese Medical Sciences(No.2016XL011).
文摘BACKGROUND Recent research suggests that although prokinetic agents,acid suppressors,and radical treatment for Helicobacter pylori infection may be effective in patients with functional dyspepsia(FD),a large proportion of patients still fail to respond to these treatments or may suffer from severe adverse reactions.Many traditional Chinese medicinal herbs can regulate the status of the entire body and have special advantages in the treatment of functional diseases.The present study was designed to verify the efficacy of Biling Weitong Granules(BLWTG),a traditional Chinese medicinal herbal compound formula,in alleviating epigastric pain syndrome(EPS)in FD patients,in an attempt to provide an effective prescription for the clinical treatment of this disease.AIM To evaluate the clinical efficacy and safety of BLWTG in treating EPS in patients with FD.METHODS In this multicenter,stratified,randomized,double-blind,placebo-controlled,parallel group clinical trial,eligible patients were randomized into the BLWTG and placebo groups who were treated for 6 wk.Efficacy indicators including the severity and frequency of EPS and the time to pain resolution and safety indicators including adverse events were observed and compared.RESULTS The baseline demographic data and clinical characteristics,such as epigastric pain symptoms,pain intensity,and frequency of attacks,were matched between the two groups before randomization.After 6 wk of treatment and after the center effect was eliminated,the epigastric pain was significantly improved in 28.33%and 85.59%of the patients in the placebo and BLWTG groups,respectively(P<0.05).At 6 wk,the resolution rate of epigastric pain was 15%and 69.49%in the placebo and BLWTG groups,respectively(P<0.05).The differences of total FD clinical score between these two groups were significant(P<0.05)at 2,4,and 6 wk(P<0.05).The scores of each item and the total score in the Functional Digestive Disorders Quality of Life Questionnaire showed significant differences between the two groups at 6 wk after both the center and interaction effects were eliminated(P<0.05).There was no significant difference in the incidence of adverse events between the two groups,and no serious adverse event was noted during the observation.CONCLUSION Compared with placebo,BLWTG markedly improved EPS in FD patients without causing serious adverse reactions.
基金the National Natural Science Foundation of China:Based on the"miR34a/Nampt-NAD+-TAC"Pathway to Study the Mechanism of Simultaneously Treating the Phlegm and Blood Stasis in the Regulation of Glycolipid(No.81873213)Study on the Mechanism of Simultaneously Treating the Phlegm and Blood Stasis on Glycolipid Metabolism Based on Intestinal Fat Absorption Regulated by miR-34a/Stat3-Nfil3 Pathway(82074308)+1 种基金a New Mechanism of Regulating the Amino Acid Metabolism of Type 2 Diabetes Mellitus with Dissipating Phlegm-Stasis:Based on the TCA Cycle-Mediated Transformation of"α-KG→Glutamate"(82274389)by Industry-University Cooperation Project for University in Fujian Province:Preparation of Monomeric Traditional Chinese Medicine Complexes Based on Nampt's Activation of Tricarboxylic Acid Cycle and Respiratory Chain to Interfere with Glycolipid Metabolism(2022Y41010015)。
文摘OBJECTIVE:To explore the mechanism of Dangua Fang(丹瓜方,DGR)in multi-target and multi-method regulation of glycolipid metabolism based on phosphoproteomics.METHODS:Sprague-Dawley rats with normal glucose levels were randomly divided into three groups,including a conventional diet control group(Group A),high-fat-highsugar diet model group(Group B),and DGR group(Group C,high-fat-high-sugar diet containing 20.5 g DGR).After 10 weeks of intervention,the fasting blood glucose(FBG),2 h blood glucose[PBG;using the oral glucose tolerance test(OGTT)],hemoglobin A1c(HbA1c),plasma total cholesterol(TC),and triglycerides(TG)were tested,and the livers of rats were removed to calculate the liver index.Then,hepatic portal TG were tested using the Gross permanent optimization-participatiory action planning enzymatic method and phosphoproteomics was performed using liquid chromatography with tandem mass spectrometry(LC-MS/MS)analysis followed by database search and bioinformatics analysis.Finally,cell experiments were used to verify the results of phosphoproteomics.Phosphorylated mitogen-activated protein kinase kinase kinase kinase 4(MAP4k4)and phosphorylated adducin 1(ADD1)were detected using western blotting.RESULTS:DGR effectively reduced PBG,TG,and the liver index(P<0.05),and significantly decreased HbA1c,TC,and hepatic portal TG(P<0.01),showed significant hematoxylin and eosin(HE)staining,red oil O staining,and Masson staining of liver tissue.The total spectrum was 805334,matched spectrum was 260471,accounting for accounting 32.3%,peptides were 19995,modified peptides were 14671,identified proteins were 4601,quantifiable proteins were 4417,identified sites were 15749,and quantified sites were 14659.Based on the threshold of expression fold change(>1.2),DGR upregulated the modification of 228 phosphorylation sites involving 204 corresponding function proteins,and downregulated the modification of 358 phosphorylation sites involving 358 corresponding function proteins,which included correcting 75 phosphorylation sites involving 64 corresponding function proteins relating to glycolipid metabolism.Therefore,DGR improved biological tissue processes,including information storage and processing,cellular processes and signaling,and metabolism.The metabolic functions regulated by DGR mainly include energy production and conversion,carbohydrate transport and metabolism,lipid transport and metabolism,inorganic ion transport and metabolism,secondary metabolite biosynthesis,transport,and catabolism.In vitro phosphorylation validation based on cell experiments showed that the change trends in the phosphorylation level of MAP4k4 and ADD1 were consistent with that of previous phosphoproteomics studies.CONCLUSION:DGR extensively corrects the modification of phosphorylation sites to improve corresponding glycolipid metabolism-related protein expression in rats with glycolipid metabolism disorders,thereby regulating glycolipid metabolism through a multi-target and multi-method process.
