[Objectives]To observe the therapeutic effect of intragastric administration of Jiangtang Shuxin recipe on diabetic heart failure(DHF)in rats and to explore its mechanism.[Methods]Fifty SD rats were randomly divided i...[Objectives]To observe the therapeutic effect of intragastric administration of Jiangtang Shuxin recipe on diabetic heart failure(DHF)in rats and to explore its mechanism.[Methods]Fifty SD rats were randomly divided into five groups,with 10 rats in each group.DHF models were prepared in the low-dose group,high-dose group,Western medicine group,and model group except the control group.Rats in the low-dose and high-dose groups were given 1.0 and 1.5 g/(kg·d)Jiangtang Shuxin recipe suspension by gavage,respectively.Rats in the Western medicine group were given gliquidone and benazepril by gavage for 2 months,and were fed with high-fat diet.Rats in the control group were fed with ordinary diet.Fasting blood glucose(FBG),serum triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),C-reactive protein(CRP),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),creatine kinase isoenzyme(CK-MB),lactate dehydrogenase(LDH),pathological morphology of myocardial tissue,NF-κB p65 protein and IκBαprotein were compared among groups.[Results]Compared with the control group,the levels of FBG,serum TG,LDL-C,CRP,IL-6,TNF-α,CK-MB and LDH increased,while the level of serum HDL-C decreased.The myocardial tissue was seriously damaged,and the expression of NF-κB p65 protein increased,while the expression of IκBαprotein decreased in the other four gruops(all P<0.05).Compared with the model group,the levels of FBG,serum TG,LDL-C,CRP,IL-6,TNF-α,CK-MB and LDH decreased,while the serum HDL-C level increased.The myocardial tissue damage was alleviated,and the expression of NF-κB p65 protein decreased,while the expression of IκBαprotein increased in the low-dose group,high-dose group and Western medicine group(all P<0.05).Compared with the Western medicine group,the levels of FBG,serum TG,LDL-C,CRP,IL-6,TNF-α,CK-MB and LDH decreased,and the level of serum HDL-C increased in the high-dose group(all P<0.05).[Conclusions]Jiangtang Shuxin recipe has a therapeutic effect on DHF in rats,with the best effect in the high-dose group.It can not only alleviate high glucose and high fat state,but also reduce myocardial injury and inflammation,and improve the pathological morphology of myocardial cells.The mechanism may be related to its inhibition of NF-кB signaling pathway.展开更多
Background:Jinqi Jiangtang tablets(JQJT)have been approved for the treatment of type 2 diabetes mellitus(T2DM)in China for many years.Exploring the effective substances and mechanisms of JQJT is important for its clin...Background:Jinqi Jiangtang tablets(JQJT)have been approved for the treatment of type 2 diabetes mellitus(T2DM)in China for many years.Exploring the effective substances and mechanisms of JQJT is important for its clinical application and further drug research and development.This study aimed to explore the chemical basis and mechanisms of JQJT in the treatment of T2DM.Methods:With network pharmacology,we screened substances in JQJT and their possible targets,then constructed the action network and enriched the biological functions and pathways associated with the active components,and identified the potential targets and mechanisms of JQJT in the treatment of T2DM.Based on the network pharmacology data,we explored the hypoglycemic mechanisms of coptisine in JQJT through western blot and quantitative real-time polymerase chain reaction.Results:Forty-three compounds with good pharmacokinetic properties were identified in JQJT,together with 146 potential biological targets.Among these potential targets,74 were associated with treatment of T2DM.A compound-target network of the 43 compounds against T2DM was constructed.Biological process and signal pathway enrichment analysis of the network highlighted the FoxO signaling pathway.Western blot and quantitative real-time polymerase chain reaction results showed that coptisine,but not epiberberine,significantly inhibited expression of key genes involved in hepatocyte gluconeogenesis by regulating the FoxO1 signaling pathway.Conclusion:Network pharmacology analysis and cell experiments showed that coptisine regulated glucose homeostasis by inhibiting the FoxO1 signaling pathway and hepatic gluconeogenesis,which may be one of the mechanisms of JQJT in the treatment of T2DM.展开更多
Background:Si-Miao Sun wrote about the Jinqi Jiangtang tablet(JQJT)that is derived from the traditional Chinese herbal medicine Huanglian(Coptis Chinensis Franch)pills in the Essential Recipes for Emergent Use Worth A...Background:Si-Miao Sun wrote about the Jinqi Jiangtang tablet(JQJT)that is derived from the traditional Chinese herbal medicine Huanglian(Coptis Chinensis Franch)pills in the Essential Recipes for Emergent Use Worth A Thousand Gold in C.E.652.The tablet is used to treat diabetes in China owing to its powerful hypoglycemic properties.However,little is known about the metabolic mechanisms underlying these properties.Methods:Ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry-based metabolomics approach was performed to explore the metabolic mechanism of JQJT in the treatment of type 2 diabetes mellitus(T2DM).Results:The metabolomic pathway analysis and the Kyoto Encyclopedia of Genes and Genomes database were used to screen out 25 potential biomarkers and construct pertinent metabolic pathways.Five metabolites,such as allantoic acid and taurine,were downregulated and 20 metabolites were upregulated in the urine of T2DM rats.The biomarkers in the JQJT group exhibited a good callback trend.It is speculated that JQJT can alleviate T2DM by regulating the disorders of taurine,hypotaurine,phenylalanine,ascorbate,and aldarate metabolism,as well as pentose and glucuronate interconversions.Conclusion:This study will be meaningful in the clinical application of JQJT and will be valuable for further exploration of the metabolic mechanisms underlying its properties.展开更多
Background:The purpose of this research is to predict the mechanisms of the experienced prescription Jiangtang decoction for treating diabetic nephropathy based on network pharmacology,the predicted targets and pathwa...Background:The purpose of this research is to predict the mechanisms of the experienced prescription Jiangtang decoction for treating diabetic nephropathy based on network pharmacology,the predicted targets and pathways were validated by celluar experiments.Methods:The active ingredients of the experienced prescription Jiangtang decoction and their putative targets were collected from TCMSP Database and SwissTargetPrediction platform.Diabetic nephropathy-related targets were excavated from GeneCards and DisGeNET database.Then,the interactions of potential targets of the experienced prescription Jiangtang decoction with well-known diabetic nephropathy targets were used to construct the protein-protein interaction network by STRING database and Cytoscape,and screened the core targets via topological analysis.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed by Metascape platform.Finally,we conducted in vitro experiments to verify this prediction of the network pharmacology.A diabetic nephropathy model was established by treating mesangial cells with D-ribose,in which the therapeutic effects of the experienced prescription Jiangtang decoction were evaluated.CCK-8 and LDH assay were used to test cell viability and cell toxicity,cell apoptosis was evaluated by Hoechst 33258 staining,AO/EB staining,levels of ROS were detected by fluorescent probe,the expression levels of MAPK signaling pathway-associated proteins and apoptosis-related proteins Bax were measured by western blotting assay.Results:A total of 74 active ingredients contained and 871 potential identified targets were retrieved from databases.Simultaneously,803 diabetic nephropathy-associated targets were also obtained,180 overlapped targets were considered as potential therapeutic targets of the experienced prescription Jiangtang decoction against diabetic nephropathy.By constructing a protein-protein interaction network and topological analysis,57 core targets were screened.Gene Ontology analysis highlighted 1655 Gene Ontology terms main including apoptotic signaling pathway,regulation of reactive oxygen species metabolic process and positive regulation of cell migration.KEGG enrichment analysis revealed that core targets were enriched mainly in MAPK,AGE-RAGE,TNF,PI3K-Akt signaling pathways.Cellular experiments further demonstrated D-ribose decreased mesangial cells viability,increased LDH release and the ROS level,induced apoptosis and activated the p38/JNK MAPK signal pathways,while the experienced prescription Jiangtang decoction could be useful in attenuation of D-ribose-induced damage.Conclusion:Network pharmacology intuitively shows the multi-component,multi-target and multi-pathway therapeutic effects of the experienced prescription Jiangtang decoction on diabetic nephropathy.By in vitro experiment,it revealed that the experienced prescription Jiangtang decoction has potential therapeutic effects on diabetic nephropathy via alleviating oxidative stress and apoptosis.the experienced prescription Jiangtang decoction treatment significantly inhibited the D-ribose-stimulated JNK and p38 MAPK activation.展开更多
Objective To study effects of Jiangtang Fanglong Wan (glucose-lowering and deafness-preventing capsule) on hearing in an animal model of diabetes. Methods Wistar rats were used to create a diabetes model by intraperit...Objective To study effects of Jiangtang Fanglong Wan (glucose-lowering and deafness-preventing capsule) on hearing in an animal model of diabetes. Methods Wistar rats were used to create a diabetes model by intraperitoneal injection of streptozotocin (STZ, 55 mg/kg). Forty rats were randomly selected to receive Jiangtang Fanglong Wan (10 g/kg/day) through intragastric gavage (treatment group) or normal saline (control group). Auditory brainstem responses (ABRs) were recorded at Months 1, 2 and 3. Results ABR latencies and wave intervals were similar between the two groups at Month 1 (P > 0.05). ABR latencies and wave intervals were shorter in the treatment group than those of the control group at Months 2 and 3 (P < 0.05 and P < 0.01, respectively). Conclusion Our results suggest that Jiangtang Fanglong Wan may have a beneficial effect in preventing and treating hearing impairment associated with diabetes.展开更多
OBJECTIVE:To investigate the therapeutic action and mechanism of the Qizhi Jiangtang capsule(芪蛭降糖胶囊,QZJT)on diabetic kidney disease(DKD)treatment.METHODS:This experiment used db/db mice and podocytes(MPC5)to dev...OBJECTIVE:To investigate the therapeutic action and mechanism of the Qizhi Jiangtang capsule(芪蛭降糖胶囊,QZJT)on diabetic kidney disease(DKD)treatment.METHODS:This experiment used db/db mice and podocytes(MPC5)to develop DKD model.Evaluation of the effect of the QZJT on db/db mice by testing urine and blood biochemical parameters(24-h urinary albumin,serum creatinine,blood urine nitrogen),pathological kidney injury,and podocyte integrity.Moreover,autophagosomes in podocytes of DKD mice and cultured podocytes were detected using electron microscopy.Additionally,Western blotting was applied to detect the expression of podocyte marker protein(podocin),autophagy-associated proteins,and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR)signaling pathway changes in vivo and in vitro.RESULTS:QZJT significantly reduced urine protein,blood nitrogen urea,and serum creatinine and showed histological restoration of renal tissues.QZJT also significantly improved the down-regulation of podocin and foot fusion and effacement in db/db mice.QZJT increased autophagic vesicles in mice and cultured podocytes.QZJT also upregulated microtubuleassociated protein 1 light chain 3-II(LC3-II)/(LC3-I)and Beclin-1 and downregulated phosphorylated-PI3K(pPI3K),p-AKT,and p-mTOR in db/db mice and MPC5 cells.However,autophagy inhibitor 3-methyladenine partially alleviated the above effects in MPC5 cells.CONCLUSIONS:These results showed that the QZJT can enhance podocyte autophagy and ameliorate podocyte injury in DKD by inhibiting the PI3K/AKT/mTOR signaling pathway.展开更多
OBJECTIVE:To investigate the effect and mechanisms of Danzhi Jiangtang capsule(丹蛭降糖胶囊,DJC)on renal injury in streptozotocin(STZ)-induced diabetes of rats.METHODS:Sprague-Dawley rats were fed with high fat diet f...OBJECTIVE:To investigate the effect and mechanisms of Danzhi Jiangtang capsule(丹蛭降糖胶囊,DJC)on renal injury in streptozotocin(STZ)-induced diabetes of rats.METHODS:Sprague-Dawley rats were fed with high fat diet for 6 weeks followed by streptozotocin(STZ,35 mg/kg)injection.These rats were then treated with DJC(270,540 and 1080 mg/kg)daily for 8 weeks.RESULTS:A combination of high fat diet and STZ significantly increased blood glucose creatinine,urea nitrogen,and urine albumin in rats.Meanwhile,the glomerular and tubular lesions were observed in rats fed with high fat diet and injected with STZ.These biochemical and pathological changes were significantly attenuated by DJC treatments in a dose-dependent manner.Mechanistically,DJC treatments significantly decreased toll-like receptor 4(TLR4),mitogen-activated protein kinase(MAPK),and nuclear factor-κB(NF-κB)signals in the kidney of rats fed with high fat diet and injected with STZ.Terminal deoxynucleotidyl transferase dU TP nick end labeling staining and caspase-8 levels showed that renal apoptosis was increased in rats fed with high fat diet and injected with STZ,and this was attenuated by DJC treatments.CONCLUSIONS:DJC treatments protect against diabetic kidney disease,and the mechanism may be closely related to downregulation of TLR4/MAPK/NF-κB pathways and apoptosis.This study provides further evidence of using DJC as a potential therapeutic option for diabetic kidney disease.展开更多
目的探究参芪降糖颗粒辅治对2型糖尿病(Diabetes mellitus type 2,T2DM)患者糖脂代谢平衡的作用效果,并分析对其转化生长因子-β1(Transforming growth factor-β1,TGF-β1)、胰高糖素样肽-1(Glucagon-like peptide-1,GLP-1)的影响。方...目的探究参芪降糖颗粒辅治对2型糖尿病(Diabetes mellitus type 2,T2DM)患者糖脂代谢平衡的作用效果,并分析对其转化生长因子-β1(Transforming growth factor-β1,TGF-β1)、胰高糖素样肽-1(Glucagon-like peptide-1,GLP-1)的影响。方法选取2018年12月—2021年12月期间在四川省眉山市中医医院初诊为T2DM患者96例为研究对象,按随机数字表法分为对照组和观察组,每组各48例。对照组采取常规西药治疗,观察组在对照组基础上采用参芪降糖颗粒加以辅治。治疗4周后,观察比较两组患者临床疗效、治疗前后糖脂[空腹血糖(Fasting plasma glucose,FPG)、餐后2 h血糖(2 h postprandial glucose,2 h PG)、糖化血红蛋白(Glycosylated hemoglobin,HbA1c)以及甘油三酯(Triglyceride,TG)、总胆固醇(Total cholesterol,TC)、高密度脂蛋白胆固醇(High density lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(Low-density lipoprotein cholesterol,LDL-C)]代谢情况、TGF-β1及GLP-1水平变化,同时探究药物安全性。结果治疗后观察组显效43.75%(21/48)、总有效率95.83%(46/48)均明显高于对照组22.92%(11/48)、83.33%(40/48),差异有统计学意义(P<0.05)。治疗4周后两组患者糖代谢指标FPG、2 h PG、HbA1c和脂代谢指标TG、TC、LDL-C均较治疗前明显降低,HDL-C较治疗前明显升高,差异有统计学意义(P<0.05);且观察组糖代谢指标FPG、2 h PG、HbA1c和脂代谢指标TG、TC、LDL-C均低于对照组,HDL-C高于对照组,差异有统计学意义(P<0.05)。治疗4周后两组患者TGF-β1水平较治疗前降低,GLP-1水平较治疗前升高,差异有统计学意义(P<0.05);且观察组TGF-β1水平低于对照组,GLP-1水平高于对照组,差异有统计学意义(P<0.05)。时点效应可显著影两项指标水平,且两项指标随时点变化趋势受到治疗方法的干预(P<0.05)。结论在西药基础上辅以参芪降糖颗粒可以明显降低T2DM患者的血糖和血脂水平,有效改善机体糖脂代谢和胰岛素代谢,从而提高整体疗效。展开更多
OBJECTIVE:To elucidate whether Danzhi Jiangtang capsule(丹蛭降糖胶囊,DJC)has treatment effects on diabetic periodontitis and the potential mechanism.METHODS:One week after the induction of diabetes by streptozotocin(S...OBJECTIVE:To elucidate whether Danzhi Jiangtang capsule(丹蛭降糖胶囊,DJC)has treatment effects on diabetic periodontitis and the potential mechanism.METHODS:One week after the induction of diabetes by streptozotocin(STZ),60 male Wistar rats were ligated by orthodontic ligation thread in cervical portion of bilateral maxillary first molar to induce diabetic periodontitis.Periodontitis was exanimated by tooth tissue morphology after 4 weeks.And then all rats were divided into 5 groups:diabetic periodontitis group(DP,n=20),periodontal basic treatment group(DP+BT,n=20),periodontal basic treatment+DJC treatment group(DP+BT+DJC,n=20)and additional Wnt/β-catenin inhibitor group(DP+BT+DJC+WIKI4/21 H7,n=20).Eight weeks after different interventions,fasting plasma glucose(FPG),C-peptide and glycosylated hemoglobin(Hb Alc)of rats were measured and then all rats were sacrificed.The paraffin sections of periodontal tissue were executed hematoxylin-eosin(HE)staining and immunohistochemical examination.The m RNA and protein levels of inflammatory cytokines were evaluated by quantitative polymerase chain reaction(Q-PCR)and Western blotting(WB).The protein levels of Wnt/β-catenin signaling molecules were measured by WB.RESULTS:The blood glucose and C-peptide concentrations in DP,DP+BT and DP+BT+DJC groups were gradually reduced,with gradually decreased distance of CEJ-A and the percentage of periodontal ligament(PDL),as well as gradually increased Hb Alc.The number of monocytes and leukocytes in the junctional epithelium and periodontal connective tissue was markedly decreased in DP+BT+DJC group(P<0.05),which was slightly reduced in DP+BT group comparing to DP group.The protein levels of Wnt1 andβ-catenin were obviously up-regulated with DJC treatment,while the SOST and DDK1 were markedly down-regulated with DJC treatment.The expression levels of BGP were lowest in DP group and highest in DP+BT+DJC group,while the tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ)and metalloproteinase-3(MMP-3)were highest in DP group and lowest in DP+BT+DJC group.All these changes could be reversed by Wnt/β-catenin inhibitor.CONCLUSION:DJC can improve the hyperglycemia and both distal alveolar bone loss and alveolar bone loss in furcation area of diabetic periodontitis rats by reducing the inflammation of gingival tissue and regulating the expressions of BGP,TNF-α,IFN-γand MMP-3 potentially through Wnt/β-catenin signaling.展开更多
OBJECTIVE: To evaluate the antioxidant capacity of the extract from Jiangtang Xiaozhi recipe(JXR) of in vitro.METHODS: JXR extract was prepared according to previously reported method. In vitro antioxidant assays were...OBJECTIVE: To evaluate the antioxidant capacity of the extract from Jiangtang Xiaozhi recipe(JXR) of in vitro.METHODS: JXR extract was prepared according to previously reported method. In vitro antioxidant assays were used in this experiment, including 1,1-Diphenyl-2-picrylhydrazyl free radical(DPPH) radical scavenging ability, 2-2’-Azinobis-(3-ethylbenzthiazoline-6-sul phonate(ABTS) radical scavenging ability, reducing power assay, fluorescence recovery after photo bleaching assay, β-carotene bleaching assay, ferric thiocyanate assay, and thiobarbituric acid method.RESULTS: DPPH, ABTS assay showed that JXR extract had distinct effect on scavenging free radicals;reducing power and ferricreducing-antioxidant power assay showed that JXR extract possessed redox ability;β-Carotene bleaching assay and antioxidant activity in a linoleic acid system using ferric thiocyanate method, thiobarbituric acid assay indicated that JXR extract could effectively inhibit lipid peroxidation, and the effect was better than that of Vitamin C.CONCLUSION: JXR extract has significant antioxidant capacity in vitro.展开更多
文摘[Objectives]To observe the therapeutic effect of intragastric administration of Jiangtang Shuxin recipe on diabetic heart failure(DHF)in rats and to explore its mechanism.[Methods]Fifty SD rats were randomly divided into five groups,with 10 rats in each group.DHF models were prepared in the low-dose group,high-dose group,Western medicine group,and model group except the control group.Rats in the low-dose and high-dose groups were given 1.0 and 1.5 g/(kg·d)Jiangtang Shuxin recipe suspension by gavage,respectively.Rats in the Western medicine group were given gliquidone and benazepril by gavage for 2 months,and were fed with high-fat diet.Rats in the control group were fed with ordinary diet.Fasting blood glucose(FBG),serum triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),C-reactive protein(CRP),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),creatine kinase isoenzyme(CK-MB),lactate dehydrogenase(LDH),pathological morphology of myocardial tissue,NF-κB p65 protein and IκBαprotein were compared among groups.[Results]Compared with the control group,the levels of FBG,serum TG,LDL-C,CRP,IL-6,TNF-α,CK-MB and LDH increased,while the level of serum HDL-C decreased.The myocardial tissue was seriously damaged,and the expression of NF-κB p65 protein increased,while the expression of IκBαprotein decreased in the other four gruops(all P<0.05).Compared with the model group,the levels of FBG,serum TG,LDL-C,CRP,IL-6,TNF-α,CK-MB and LDH decreased,while the serum HDL-C level increased.The myocardial tissue damage was alleviated,and the expression of NF-κB p65 protein decreased,while the expression of IκBαprotein increased in the low-dose group,high-dose group and Western medicine group(all P<0.05).Compared with the Western medicine group,the levels of FBG,serum TG,LDL-C,CRP,IL-6,TNF-α,CK-MB and LDH decreased,and the level of serum HDL-C increased in the high-dose group(all P<0.05).[Conclusions]Jiangtang Shuxin recipe has a therapeutic effect on DHF in rats,with the best effect in the high-dose group.It can not only alleviate high glucose and high fat state,but also reduce myocardial injury and inflammation,and improve the pathological morphology of myocardial cells.The mechanism may be related to its inhibition of NF-кB signaling pathway.
基金the Fundamental Research Funds for the Central Universities(grant number:2021-JYB-XJSJJ-003)the Open Project of State Key Laboratory of Bioactive Substance and Function of Natural Medicines(grant number:GTZK202108)+1 种基金Chinese Society of Toxicology(grant number:CST2021CT101)Discipline Construction Project of Peking Union Medical College(grant number:201920200801).
文摘Background:Jinqi Jiangtang tablets(JQJT)have been approved for the treatment of type 2 diabetes mellitus(T2DM)in China for many years.Exploring the effective substances and mechanisms of JQJT is important for its clinical application and further drug research and development.This study aimed to explore the chemical basis and mechanisms of JQJT in the treatment of T2DM.Methods:With network pharmacology,we screened substances in JQJT and their possible targets,then constructed the action network and enriched the biological functions and pathways associated with the active components,and identified the potential targets and mechanisms of JQJT in the treatment of T2DM.Based on the network pharmacology data,we explored the hypoglycemic mechanisms of coptisine in JQJT through western blot and quantitative real-time polymerase chain reaction.Results:Forty-three compounds with good pharmacokinetic properties were identified in JQJT,together with 146 potential biological targets.Among these potential targets,74 were associated with treatment of T2DM.A compound-target network of the 43 compounds against T2DM was constructed.Biological process and signal pathway enrichment analysis of the network highlighted the FoxO signaling pathway.Western blot and quantitative real-time polymerase chain reaction results showed that coptisine,but not epiberberine,significantly inhibited expression of key genes involved in hepatocyte gluconeogenesis by regulating the FoxO1 signaling pathway.Conclusion:Network pharmacology analysis and cell experiments showed that coptisine regulated glucose homeostasis by inhibiting the FoxO1 signaling pathway and hepatic gluconeogenesis,which may be one of the mechanisms of JQJT in the treatment of T2DM.
基金supported by the National Key Research and Development Program of China(No.2020YFF01014606)the National Natural Science Foundation of China(No.82073741).
文摘Background:Si-Miao Sun wrote about the Jinqi Jiangtang tablet(JQJT)that is derived from the traditional Chinese herbal medicine Huanglian(Coptis Chinensis Franch)pills in the Essential Recipes for Emergent Use Worth A Thousand Gold in C.E.652.The tablet is used to treat diabetes in China owing to its powerful hypoglycemic properties.However,little is known about the metabolic mechanisms underlying these properties.Methods:Ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry-based metabolomics approach was performed to explore the metabolic mechanism of JQJT in the treatment of type 2 diabetes mellitus(T2DM).Results:The metabolomic pathway analysis and the Kyoto Encyclopedia of Genes and Genomes database were used to screen out 25 potential biomarkers and construct pertinent metabolic pathways.Five metabolites,such as allantoic acid and taurine,were downregulated and 20 metabolites were upregulated in the urine of T2DM rats.The biomarkers in the JQJT group exhibited a good callback trend.It is speculated that JQJT can alleviate T2DM by regulating the disorders of taurine,hypotaurine,phenylalanine,ascorbate,and aldarate metabolism,as well as pentose and glucuronate interconversions.Conclusion:This study will be meaningful in the clinical application of JQJT and will be valuable for further exploration of the metabolic mechanisms underlying its properties.
基金This study was supported by the National Natural Science Foundation of China(grants 81573763)Beijing Municipal Natural Science Foundation(grants 7172221)Beijing Traditional Chinese Medicine Science and Technology Development Project(JJ-2020-03).
文摘Background:The purpose of this research is to predict the mechanisms of the experienced prescription Jiangtang decoction for treating diabetic nephropathy based on network pharmacology,the predicted targets and pathways were validated by celluar experiments.Methods:The active ingredients of the experienced prescription Jiangtang decoction and their putative targets were collected from TCMSP Database and SwissTargetPrediction platform.Diabetic nephropathy-related targets were excavated from GeneCards and DisGeNET database.Then,the interactions of potential targets of the experienced prescription Jiangtang decoction with well-known diabetic nephropathy targets were used to construct the protein-protein interaction network by STRING database and Cytoscape,and screened the core targets via topological analysis.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed by Metascape platform.Finally,we conducted in vitro experiments to verify this prediction of the network pharmacology.A diabetic nephropathy model was established by treating mesangial cells with D-ribose,in which the therapeutic effects of the experienced prescription Jiangtang decoction were evaluated.CCK-8 and LDH assay were used to test cell viability and cell toxicity,cell apoptosis was evaluated by Hoechst 33258 staining,AO/EB staining,levels of ROS were detected by fluorescent probe,the expression levels of MAPK signaling pathway-associated proteins and apoptosis-related proteins Bax were measured by western blotting assay.Results:A total of 74 active ingredients contained and 871 potential identified targets were retrieved from databases.Simultaneously,803 diabetic nephropathy-associated targets were also obtained,180 overlapped targets were considered as potential therapeutic targets of the experienced prescription Jiangtang decoction against diabetic nephropathy.By constructing a protein-protein interaction network and topological analysis,57 core targets were screened.Gene Ontology analysis highlighted 1655 Gene Ontology terms main including apoptotic signaling pathway,regulation of reactive oxygen species metabolic process and positive regulation of cell migration.KEGG enrichment analysis revealed that core targets were enriched mainly in MAPK,AGE-RAGE,TNF,PI3K-Akt signaling pathways.Cellular experiments further demonstrated D-ribose decreased mesangial cells viability,increased LDH release and the ROS level,induced apoptosis and activated the p38/JNK MAPK signal pathways,while the experienced prescription Jiangtang decoction could be useful in attenuation of D-ribose-induced damage.Conclusion:Network pharmacology intuitively shows the multi-component,multi-target and multi-pathway therapeutic effects of the experienced prescription Jiangtang decoction on diabetic nephropathy.By in vitro experiment,it revealed that the experienced prescription Jiangtang decoction has potential therapeutic effects on diabetic nephropathy via alleviating oxidative stress and apoptosis.the experienced prescription Jiangtang decoction treatment significantly inhibited the D-ribose-stimulated JNK and p38 MAPK activation.
文摘Objective To study effects of Jiangtang Fanglong Wan (glucose-lowering and deafness-preventing capsule) on hearing in an animal model of diabetes. Methods Wistar rats were used to create a diabetes model by intraperitoneal injection of streptozotocin (STZ, 55 mg/kg). Forty rats were randomly selected to receive Jiangtang Fanglong Wan (10 g/kg/day) through intragastric gavage (treatment group) or normal saline (control group). Auditory brainstem responses (ABRs) were recorded at Months 1, 2 and 3. Results ABR latencies and wave intervals were similar between the two groups at Month 1 (P > 0.05). ABR latencies and wave intervals were shorter in the treatment group than those of the control group at Months 2 and 3 (P < 0.05 and P < 0.01, respectively). Conclusion Our results suggest that Jiangtang Fanglong Wan may have a beneficial effect in preventing and treating hearing impairment associated with diabetes.
基金National Natural Science Foundation of China Project:Experimental Research on Podocyte Autophagy of Diabetic Nephropathy Regulated by Qizhi Jiangtang Capusul(No.81874440)Natural Science Foundation of Shandong Province Project:Curcumin Ameliorates Diabetic Nephropathy via Regulating the Intestinal Barrier-Inflammation“cross-talk”(ZR2020QH063)。
文摘OBJECTIVE:To investigate the therapeutic action and mechanism of the Qizhi Jiangtang capsule(芪蛭降糖胶囊,QZJT)on diabetic kidney disease(DKD)treatment.METHODS:This experiment used db/db mice and podocytes(MPC5)to develop DKD model.Evaluation of the effect of the QZJT on db/db mice by testing urine and blood biochemical parameters(24-h urinary albumin,serum creatinine,blood urine nitrogen),pathological kidney injury,and podocyte integrity.Moreover,autophagosomes in podocytes of DKD mice and cultured podocytes were detected using electron microscopy.Additionally,Western blotting was applied to detect the expression of podocyte marker protein(podocin),autophagy-associated proteins,and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR)signaling pathway changes in vivo and in vitro.RESULTS:QZJT significantly reduced urine protein,blood nitrogen urea,and serum creatinine and showed histological restoration of renal tissues.QZJT also significantly improved the down-regulation of podocin and foot fusion and effacement in db/db mice.QZJT increased autophagic vesicles in mice and cultured podocytes.QZJT also upregulated microtubuleassociated protein 1 light chain 3-II(LC3-II)/(LC3-I)and Beclin-1 and downregulated phosphorylated-PI3K(pPI3K),p-AKT,and p-mTOR in db/db mice and MPC5 cells.However,autophagy inhibitor 3-methyladenine partially alleviated the above effects in MPC5 cells.CONCLUSIONS:These results showed that the QZJT can enhance podocyte autophagy and ameliorate podocyte injury in DKD by inhibiting the PI3K/AKT/mTOR signaling pathway.
基金Supported by the Research Grant from the National Natural Science Foundation of China:Mechanism of Danzhi Jiangtang Capsule Regulating Adipocyte-derived Exosomes in the Prevention and Treatment of Type 2 Diabetes Mellitus Macrovascular Disease(No.82174153)Based on Chip Technology to Carry out Basic and Clinical Comparison to Explore the Research of Danzhi Jiangtang Capsule in Precise Treatment of Diabetic Macrovascular Disease(No.81774286)。
文摘OBJECTIVE:To investigate the effect and mechanisms of Danzhi Jiangtang capsule(丹蛭降糖胶囊,DJC)on renal injury in streptozotocin(STZ)-induced diabetes of rats.METHODS:Sprague-Dawley rats were fed with high fat diet for 6 weeks followed by streptozotocin(STZ,35 mg/kg)injection.These rats were then treated with DJC(270,540 and 1080 mg/kg)daily for 8 weeks.RESULTS:A combination of high fat diet and STZ significantly increased blood glucose creatinine,urea nitrogen,and urine albumin in rats.Meanwhile,the glomerular and tubular lesions were observed in rats fed with high fat diet and injected with STZ.These biochemical and pathological changes were significantly attenuated by DJC treatments in a dose-dependent manner.Mechanistically,DJC treatments significantly decreased toll-like receptor 4(TLR4),mitogen-activated protein kinase(MAPK),and nuclear factor-κB(NF-κB)signals in the kidney of rats fed with high fat diet and injected with STZ.Terminal deoxynucleotidyl transferase dU TP nick end labeling staining and caspase-8 levels showed that renal apoptosis was increased in rats fed with high fat diet and injected with STZ,and this was attenuated by DJC treatments.CONCLUSIONS:DJC treatments protect against diabetic kidney disease,and the mechanism may be closely related to downregulation of TLR4/MAPK/NF-κB pathways and apoptosis.This study provides further evidence of using DJC as a potential therapeutic option for diabetic kidney disease.
文摘目的探究参芪降糖颗粒辅治对2型糖尿病(Diabetes mellitus type 2,T2DM)患者糖脂代谢平衡的作用效果,并分析对其转化生长因子-β1(Transforming growth factor-β1,TGF-β1)、胰高糖素样肽-1(Glucagon-like peptide-1,GLP-1)的影响。方法选取2018年12月—2021年12月期间在四川省眉山市中医医院初诊为T2DM患者96例为研究对象,按随机数字表法分为对照组和观察组,每组各48例。对照组采取常规西药治疗,观察组在对照组基础上采用参芪降糖颗粒加以辅治。治疗4周后,观察比较两组患者临床疗效、治疗前后糖脂[空腹血糖(Fasting plasma glucose,FPG)、餐后2 h血糖(2 h postprandial glucose,2 h PG)、糖化血红蛋白(Glycosylated hemoglobin,HbA1c)以及甘油三酯(Triglyceride,TG)、总胆固醇(Total cholesterol,TC)、高密度脂蛋白胆固醇(High density lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(Low-density lipoprotein cholesterol,LDL-C)]代谢情况、TGF-β1及GLP-1水平变化,同时探究药物安全性。结果治疗后观察组显效43.75%(21/48)、总有效率95.83%(46/48)均明显高于对照组22.92%(11/48)、83.33%(40/48),差异有统计学意义(P<0.05)。治疗4周后两组患者糖代谢指标FPG、2 h PG、HbA1c和脂代谢指标TG、TC、LDL-C均较治疗前明显降低,HDL-C较治疗前明显升高,差异有统计学意义(P<0.05);且观察组糖代谢指标FPG、2 h PG、HbA1c和脂代谢指标TG、TC、LDL-C均低于对照组,HDL-C高于对照组,差异有统计学意义(P<0.05)。治疗4周后两组患者TGF-β1水平较治疗前降低,GLP-1水平较治疗前升高,差异有统计学意义(P<0.05);且观察组TGF-β1水平低于对照组,GLP-1水平高于对照组,差异有统计学意义(P<0.05)。时点效应可显著影两项指标水平,且两项指标随时点变化趋势受到治疗方法的干预(P<0.05)。结论在西药基础上辅以参芪降糖颗粒可以明显降低T2DM患者的血糖和血脂水平,有效改善机体糖脂代谢和胰岛素代谢,从而提高整体疗效。
基金Supported by the Education Science Foundation of Anhui Province(Intervention Study on Periodontal Tissue in Rats with Experimental Diabetic Periodontitis in Danzhi Jiangtang Capsule,No.KJ2015A429)。
文摘OBJECTIVE:To elucidate whether Danzhi Jiangtang capsule(丹蛭降糖胶囊,DJC)has treatment effects on diabetic periodontitis and the potential mechanism.METHODS:One week after the induction of diabetes by streptozotocin(STZ),60 male Wistar rats were ligated by orthodontic ligation thread in cervical portion of bilateral maxillary first molar to induce diabetic periodontitis.Periodontitis was exanimated by tooth tissue morphology after 4 weeks.And then all rats were divided into 5 groups:diabetic periodontitis group(DP,n=20),periodontal basic treatment group(DP+BT,n=20),periodontal basic treatment+DJC treatment group(DP+BT+DJC,n=20)and additional Wnt/β-catenin inhibitor group(DP+BT+DJC+WIKI4/21 H7,n=20).Eight weeks after different interventions,fasting plasma glucose(FPG),C-peptide and glycosylated hemoglobin(Hb Alc)of rats were measured and then all rats were sacrificed.The paraffin sections of periodontal tissue were executed hematoxylin-eosin(HE)staining and immunohistochemical examination.The m RNA and protein levels of inflammatory cytokines were evaluated by quantitative polymerase chain reaction(Q-PCR)and Western blotting(WB).The protein levels of Wnt/β-catenin signaling molecules were measured by WB.RESULTS:The blood glucose and C-peptide concentrations in DP,DP+BT and DP+BT+DJC groups were gradually reduced,with gradually decreased distance of CEJ-A and the percentage of periodontal ligament(PDL),as well as gradually increased Hb Alc.The number of monocytes and leukocytes in the junctional epithelium and periodontal connective tissue was markedly decreased in DP+BT+DJC group(P<0.05),which was slightly reduced in DP+BT group comparing to DP group.The protein levels of Wnt1 andβ-catenin were obviously up-regulated with DJC treatment,while the SOST and DDK1 were markedly down-regulated with DJC treatment.The expression levels of BGP were lowest in DP group and highest in DP+BT+DJC group,while the tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ)and metalloproteinase-3(MMP-3)were highest in DP group and lowest in DP+BT+DJC group.All these changes could be reversed by Wnt/β-catenin inhibitor.CONCLUSION:DJC can improve the hyperglycemia and both distal alveolar bone loss and alveolar bone loss in furcation area of diabetic periodontitis rats by reducing the inflammation of gingival tissue and regulating the expressions of BGP,TNF-α,IFN-γand MMP-3 potentially through Wnt/β-catenin signaling.
基金Supported by The Special Project for Academic Construction of Peking Union Medical CollegeBeijing(Traditional Chinese Medicine Cultural Construction for Heritage in Chinese Union of Medicinal Plant Gardens,Tsinghua,211-201920100902)Beijing Natural Science Foundation(The molecular mechanism of the retinal pericyte protection by Jangtang Xiaozhi Tablets in STZ induced diabetic rats,No.7152100)。
文摘OBJECTIVE: To evaluate the antioxidant capacity of the extract from Jiangtang Xiaozhi recipe(JXR) of in vitro.METHODS: JXR extract was prepared according to previously reported method. In vitro antioxidant assays were used in this experiment, including 1,1-Diphenyl-2-picrylhydrazyl free radical(DPPH) radical scavenging ability, 2-2’-Azinobis-(3-ethylbenzthiazoline-6-sul phonate(ABTS) radical scavenging ability, reducing power assay, fluorescence recovery after photo bleaching assay, β-carotene bleaching assay, ferric thiocyanate assay, and thiobarbituric acid method.RESULTS: DPPH, ABTS assay showed that JXR extract had distinct effect on scavenging free radicals;reducing power and ferricreducing-antioxidant power assay showed that JXR extract possessed redox ability;β-Carotene bleaching assay and antioxidant activity in a linoleic acid system using ferric thiocyanate method, thiobarbituric acid assay indicated that JXR extract could effectively inhibit lipid peroxidation, and the effect was better than that of Vitamin C.CONCLUSION: JXR extract has significant antioxidant capacity in vitro.
