Background:Erzhu Erchen decoction(EZECD),which is based on Erchen decoction and enhanced with Atractylodes lancea and Atractylodes macrocephala,is widely used for the treatment of dampness and heat(The clinical manife...Background:Erzhu Erchen decoction(EZECD),which is based on Erchen decoction and enhanced with Atractylodes lancea and Atractylodes macrocephala,is widely used for the treatment of dampness and heat(The clinical manifestations of Western medicine include thirst,inability to drink more,diarrhea,yellow urine,red tongue,et al.)internalized disease.Nevertheless,the mechanism of EZECD on damp-heat internalized Type 2 diabetes(T2D)remains unknown.We employed data mining,pharmacology databases and experimental verification to study how EZECD treats damp-heat internalized T2D.Methods:The main compounds or genes of EZECD and damp-heat internalized T2D were obtained from the pharmacology databases.Succeeding,the overlapped targets of EZECD and damp-heat internalized T2D were performed by the Gene Ontology,kyoto encyclopedia of genes and genomes analysis.And the compound-disease targets-pathway network were constructed to obtain the hub compound.Moreover,the hub genes and core related pathways were mined with weighted gene co-expression network analysis based on Gene Expression Omnibus database,the capability of hub compound and genes was valid in AutoDock 1.5.7.Furthermore,and violin plot and gene set enrichment analysis were performed to explore the role of hub genes in damp-heat internalized T2D.Finally,the interactions of hub compound and genes were explored using Comparative Toxicogenomics Database and quantitative polymerase chain reaction.Results:First,herb-compounds-genes-disease network illustrated that the hub compound of EZECD for damp-heat internalized T2D could be quercetin.Consistently,the hub genes were CASP8,CCL2,and AHR according to weighted gene co-expression network analysis.Molecular docking showed that quercetin could bind with the hub genes.Further,gene set enrichment analysis and Gene Ontology represented that CASP8,or CCL2,is negatively involved in insulin secretion response to the TNF or lipopolysaccharide process,and AHR or CCL2 positively regulated lipid and atherosclerosis,and/or including NOD-like receptor signaling pathway,and TNF signaling pathway.Ultimately,the quantitative polymerase chain reaction and western blotting analysis showed that quercetin could down-regulated the mRNA and protein experssion of CASP8,CCL2,and AHR.It was consistent with the results in Comparative Toxicogenomics Database databases.Conclusion:These results demonstrated quercetin could inhibit the expression of CASP8,CCL2,AHR in damp-heat internalized T2D,which improves insulin secretion and inhibits lipid and atherosclerosis,as well as/or including NOD-like receptor signaling pathway,and TNF signaling pathway,suggesting that EZECD may be more effective to treat damp-heat internalized T2D.展开更多
[Objectives]To explore the mechanism of Gegen Qinlian Decoction in treating type 2 diabetes mellitus(T2DM)complicated with non-alcoholic fatty liver disease(NAFLD)by analyzing the effective components of Gegen Qinlian...[Objectives]To explore the mechanism of Gegen Qinlian Decoction in treating type 2 diabetes mellitus(T2DM)complicated with non-alcoholic fatty liver disease(NAFLD)by analyzing the effective components of Gegen Qinlian Decoction.[Methods]TCMSP database was used to analyze the active components of Gegen Qinlian Decoction,and pubchem and Swiss ADME databases were also used to predict drug targets,extract T2DM complicated with NAFLD targets from OMIM and Genecards databases.Venny plot was drawn to obtain intersection targets,and finally Cytoscape was used to make core target maps and drug-target-disease network maps.Using DAVID and Metascape database to analyze the intersection targets,the gene ontology information of Go and KEGG was obtained.Microbial informatics technology was used to visualize GO,and Cytoscape was used to make drug-target-disease network map-enrichment pathway map.[Results]The network pharmacological analysis showed that Gegen Qinlian Decoction acted on the key targets of type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease,such as ALB and ALT1,through many components,and achieved the purpose of treating this disease.The chemical constituents of the drug include formononetin,5-hydroxyisomucronulatol-2,5-2-O-glucoside,cholesteryl laurate,isoliquiritigenin,etc.[Conclusions]This study provides a new idea and theoretical support for future drug research and clinical practice.展开更多
Background:The development and prognosis of breast cancer are intricately linked to psychological stress.In addition,depression is the most common psychological comorbidity among breast cancer survivors,and reportedly...Background:The development and prognosis of breast cancer are intricately linked to psychological stress.In addition,depression is the most common psychological comorbidity among breast cancer survivors,and reportedly,Fang-Xia-Dihuang decoction(FXDH)can effectively manage depression in such patients.However,its pharmacological and molecular mechanisms remain obscure.Methods:Public databases were used for obtaining active components and related targets.Main active components were further verified by ultra-high-performance liquid chromatography-high-resolution mass spectrometry(UPLC-HRMS).Protein–protein interaction and enrichment analyses were taken to predict potential hub targets and related pathways.Molecule docking was used to understand the interactions between main compounds and hub targets.In addition,an animal model of breast cancer combined with depression was established to evaluate the intervention effect of FXDH and verify the pathways screened by network pharmacology.Results:174 active components of FXDH and 163 intersection targets of FXDH,breast cancer,and depression were identified.Quercetin,methyl ferulate,luteolin,ferulaldehyde,wogonin,and diincarvilone were identified as the principal active components of FXDH.Protein–protein interaction and KEGG enrichment analyses revealed that the phosphoinositide-3-kinase–protein kinase B(PI3K/AKT)and Janus kinase/signal transducer and activator of transcription(JAK2/STAT3)signaling pathways played a crucial role in mediating the efficacy of FXDH for inhibiting breast cancer progression induced by depression.In addition,in vivo experiments revealed that FXDH ameliorated depression-like behavior in mice and inhibited excessive tumor growth in mice with breast cancer and depression.FXDH treatment downregulated the expression of epinephrine,PI3K,AKT,STAT3,and JAK2 compared with the control treatment(p<0.05).Molecular docking verified the relationship between the six primary components of FXDH and the three most important targets,including phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA),AKT,and STAT3.Conclusion:This study provides a scientific basis to support the clinical application of FXDH for improving depression-like behavior and inhibiting breast cancer progression promoted by chronic stress.The therapeutic effects FXDH may be closely related to the PI3K/AKT and JAK2/STAT3 pathways.This finding helps better understand the regulatory mechanisms underlying the efficacy of FXDH.展开更多
Background:This study will be aimed at investigating the effects of Baihu Renshen decoction(BHRS)on type 2 diabetes rats and on macromolecular enzyme 1(PINK1)/E3 ubiquitin protein ligase(Parkin)pathway.Methods:The exp...Background:This study will be aimed at investigating the effects of Baihu Renshen decoction(BHRS)on type 2 diabetes rats and on macromolecular enzyme 1(PINK1)/E3 ubiquitin protein ligase(Parkin)pathway.Methods:The experiment was divided into four groups:control group,model group,metformin group and BHRS low-dose group and high-dose group.Forty male rats were selected as samples and randomly assigned to at least one test group.Finally,there are 18 rats in each group.Except for the control group,the rats within the different teams got a high-fat diet associate in nursing an intraperitoneal injection of streptozotocin to make a type 2 diabetes mellitus(T2DM)rat model.The organic chemistry and inflammatory indexes of rats in every cluster were analyzed and compared once four weeks of intragastric administration of comparable reagents to review the therapeutic impact of BHRS on T2DM.In addition,we determined the pathological changes of ductal gland tissue of T2DM rats after treatment,and compared the expression of mitochondrial phagocytosis related proteins in ductal gland tissue of rats in each group.Results:FBG,LDL-C,TC,TG,MDA,IL-1,IL-6,TNF-,and mitophagy-related proteins COXIV,P62,VDAC1,and TOM20 were elevated in the model group compared to the control group,while HDL-C,SOD,GSH-Px,and mitophagy-related proteins PINK1,Parkin,and LC3II/I were decreased(P<0.05 or P<0.01).The expressions of FBG,TC,TG,LDL-C,MDA,IL-1,IL-6,TNF-,and mitophagy-related proteins COXIV,P62,VDAC1,and TOM20 were lowered in the BHRS group,while the expressions of HOMA-,HDL-C,SOD,GSH-Px,and mitophagy-related proteins PINK1,Parkin,and LC3II/I were(P<0.05 or P<0.01).After therapy with BHRS,hematoxylin-eosin staining showed that the intensity of pancreatic acinar staining increased,and islet cells became clear boundaries that were,regularly arranged,and with reduced vacuoles reduced.Conclusion:BHRS has a clear therapeutic effect on T2DM,which may be achieved by regulating mitochondrial autophagy through the PINK1/Parkin pathway.展开更多
Objective:To observe the effect of Qishen decoction on macrophage polarization mediated by miR-495/FTO signaling pathway,and to clarify the molecular mechanism of Qishen decoction in improving insulin resistance in th...Objective:To observe the effect of Qishen decoction on macrophage polarization mediated by miR-495/FTO signaling pathway,and to clarify the molecular mechanism of Qishen decoction in improving insulin resistance in the treatment of type 2 diabetes.Methods:THP-1 was induced to differentiate macrophages with phorbol ester.It was divided into the control group,the model group,the Qishen decoction group,the miR-495 inhibitor group,and the Qishen decoction+miR-495 inhibitor group.Except for the control group,the remaining groups were stimulated with 30 mmol/L glucose to construct a macrophage polarization model,and corresponding drugs were given for intervention.Cells were collected from each group for 24 hours and the content of inflammatory factors(IL-6,IL-1β,IL-4,and IL-10)were detected using enzyme-linked immunosorbent assay.The expression of macrophage polarization marker molecules,miR-495,and FTO were detected by flow cytometry,qPCR,and Western blot to detect.Results:Compared with the control group,there was no significant change in the activity of macrophages in the control serum,Qishen decoction containing serum,and miR-495 inhibitor transfected serum,and the difference was not statistically significant(P>0.05).In addition,compared to the control group,the content of IL-6 and IL-1β,the expression levels of CD68,iNOS,COX-2,miR-495,and the ratio of CD68/CD206,were significantly increased(P<0.01).While the content of IL-4 and IL-10,as well as the expression of CD206,Arg-1,YM-1,and FTO were significantly reduced(P<0.01).Compared with the model group,the QiShen decoction significantly reduced the contents of IL-6 and IL-1β,and the expression levels of CD68,iNOS,COX-2,and miR-495,as well as the ratio of CD68/CD206,while the content of IL-4 and IL-10,as well as the expression of CD206,Arg-1,YM-1,and FTO were significantly increased(P<0.01).Conclusion:Qishen decoction upregulate the expression of FTO to promote M2 type polarization of macrophages,thereby inhibiting inflammation and improving insulin resistance by inhibiting the expression of miR-495.展开更多
目的探讨胃衡汤调控核因子E2相关因子2(Nrf2)-Kelch样环氧氯丙烷相关蛋白(Keap)信号通路抑制老年胃癌前病变(Precancerous lesions of gastric cancer,PLGC)患者氧化应激反应的作用。方法选取2022年3月-2023年3月期间于南京中医药大学...目的探讨胃衡汤调控核因子E2相关因子2(Nrf2)-Kelch样环氧氯丙烷相关蛋白(Keap)信号通路抑制老年胃癌前病变(Precancerous lesions of gastric cancer,PLGC)患者氧化应激反应的作用。方法选取2022年3月-2023年3月期间于南京中医药大学第二附属医院消化腔镜中心和脾胃病科就诊的PLGC老年患者60例,按随机数字表法分为基础治疗组与胃衡汤治疗组,每组各30例。另选择同期常规胃镜体检的慢性浅表性胃炎患者30例为对照组。对照组仅入组接受研究相关指标检测,不予治疗。基础治疗组患者给予雷贝拉唑钠肠溶胶囊,胃衡汤组在基础治疗组上加用胃衡汤治疗,均治疗6个月。观察比较两组PLGC患者临床疗效、安全性,治疗前后中医证候评分、胃镜病理分级及Nrf2-Keap通路相关蛋白检测。结果治疗后胃衡汤治疗组中医证候疗效总有效率93.33%(28/30)明显高于基础治疗组76.67%(23/30),差异有统计学意义(P<0.05)。治疗后胃衡汤治疗组病理组织学疗效总有效率83.33%(25/30)明显高于基础治疗组63.33%(19/30),差异有统计学意义(P<0.05)。治疗后两组患者中医证候各项积分及总积分均较治疗前降低,差异有统计学意义(P<0.05);且胃衡汤治疗组中医证候各项积分及总积分均明显低于基础治疗组,差异有统计学意义(P<0.05)。治疗后两组患者胃黏膜组织学各项积分及总分均较治疗前降低,差异有统计学意义(P<0.05);且胃衡汤治疗组胃黏膜组织学各项积分及总分均明显低于基础治疗组,差异有统计学意义(P<0.05)。治疗后两组患者Nrf2和SOD表达高于治疗前,Keap1和MDA表达较治疗前降低,差异有统计学意义(P<0.05);且胃衡汤治疗组Nrf2和SOD表达明显高于基础治疗组,Keap1和MDA表达明显低于基础治疗组,差异有统计学意义(P<0.05)。治疗期间,两组患者治疗前后肝肾功能、三大常规及心电图检查均未发现异常。结论胃衡汤治疗老年PLGC能够改善临床症状,抑制甚至逆转病理学改变,提高治疗效果,其机制与调节Nrf2-Keap信号通路而抑制氧化应激反应有关。展开更多
In the present study, a human neuroblastoma cell line （SH-SY5Y） and BV-2 microglia were treated with amyloid-β peptide （25-35）, as a model of Alzheimer＇s disease, to evaluate the protective effects of 10-3-10-8 ...In the present study, a human neuroblastoma cell line （SH-SY5Y） and BV-2 microglia were treated with amyloid-β peptide （25-35）, as a model of Alzheimer＇s disease, to evaluate the protective effects of 10-3-10-8 g/mL Lingguizhugan decoction and to examine the underlying anti-inflammatory mechanism. Lingguizhugan decoction significantly enhanced the viability of SH-SY5Y cells with amyloid-β peptide-induced injury, and lowered levels of interleukin-1β, interleukin-6, tumor necrosis factor-a and nitric oxide in the culture supernatant of activated BV-2 microglia. The effects of 103 g/mL Lingguizhugan decoction were more significant. These results suggest that Lingguizhugan decoction can protect SH-SY5Y cells against amyloid-β peptide （25-35）-induced injury in a dose-dependent manner by inhibiting overexpression of inflammatory factors by activated microglia.展开更多
Summary： In order to investigate whether Yinchenhao decoction （YCHD） attenuates hepatic fibro- genesis in the bile duct ligation （BDL） model via recovering and restoring the self-regulation and bal- ance of the r...Summary： In order to investigate whether Yinchenhao decoction （YCHD） attenuates hepatic fibro- genesis in the bile duct ligation （BDL） model via recovering and restoring the self-regulation and bal- ance of the renin-angiotensin system （RAS）, 33 specific-pathogen-free （SPF） male Sprague-Dawley rats with common BDL and scission were randomly divided into five groups as follows： G1, the sham group （n=4）; G2, BDL 7-day group （n=5）; G3, BDL＋YCHD 430 mg/mL （n=8）; G4, BDL＋losartan 0.65 mg/mL （ARB group, n=8）; G5, model group （BDL without any treatment, n=8）. YCHD and losartan （10 mL.kgl.day-1） were given by gastric gavage for 16 days following BDL in G3 and G4 groups, respec- tively. The effect of YCHD on liver fibrosis and the detailed molecular mechanisms were assessed by liver function including total bilirubin （TBIL）, direct bilirubin （DBIL）, indirect bilirubin （IDBIL）, alanine aminotransferase （ALT）, and aspartate aminotransferase （AST）. Histological changes were ob-. served by transmission electron microscopy （TEM） and Masson trichrome staining. Western blotting was used to detect the protein expression level of the renin-angiotensin system （RAS） components in- cluding angiotensin converting enzyme （ACE）, angiotensin II type 1 receptor （AT1R）, ACE2, angio- tensin II （Ang II） as well as transforming growth factor 131 （TGF131）. The experimental data were ana- lyzed by principle component analytical method of pattern recognition. The results showed that bio- chemically, serum TBIL, DBIL, IDBIL, ALT and AST levels were markedly increased following BDL as compared with the sham group （P〈0.05）. Serum TBIL, IDBIL and DBIL levels in G3 group were dramatically decreased as compared with G5 and G4 groups （P〈0.05）. Serum AST level in G3 was sig- nificantly lowered than in G5 group （P〈0.05）, but there was no significant difference in ALT among G3, G4 and G5 groups （P〉0.05）. Histologically, livers in G3 group showed less hepatocytes necrosis, less bile duct hyperplasia and less collagen formation than in G4 and G5 groups. The protein expression lev- els of ACE2, ACE, Ang II, AT1R and TGF131 in G2, G3 and G4 groups were significantly higher than in sham group （P〈0.05）, and lower than in G5 group （P〈0.05）. However, the differences among G2, G3 and G4 groups were not significant （P〉0.05）. ACE2 protein expression in G3 group was significantly higher than in G2 group （P〈0.05） and there was no significant difference in comparison with G4 group （P〉0.05）. Moreover, the protein expression of TGF131 in G3 group was significantly lower than in G5 and G4 groups （P〈0.05）. Our findings suggest that the antifibrotic effects of YCHD may be associated with the decreased classical RAS pathway components and TGFI31 downexpression so as to recover and rebuild self-regulation of the RAS by elevating the protein expression of ACE2.展开更多
基金supported by a grant from Hubei Key Laboratory of Diabetes and Angiopathy Program of Hubei University of Science and Technology(2020XZ10)Project of Education Commission of Hubei Province(B2022192).
文摘Background:Erzhu Erchen decoction(EZECD),which is based on Erchen decoction and enhanced with Atractylodes lancea and Atractylodes macrocephala,is widely used for the treatment of dampness and heat(The clinical manifestations of Western medicine include thirst,inability to drink more,diarrhea,yellow urine,red tongue,et al.)internalized disease.Nevertheless,the mechanism of EZECD on damp-heat internalized Type 2 diabetes(T2D)remains unknown.We employed data mining,pharmacology databases and experimental verification to study how EZECD treats damp-heat internalized T2D.Methods:The main compounds or genes of EZECD and damp-heat internalized T2D were obtained from the pharmacology databases.Succeeding,the overlapped targets of EZECD and damp-heat internalized T2D were performed by the Gene Ontology,kyoto encyclopedia of genes and genomes analysis.And the compound-disease targets-pathway network were constructed to obtain the hub compound.Moreover,the hub genes and core related pathways were mined with weighted gene co-expression network analysis based on Gene Expression Omnibus database,the capability of hub compound and genes was valid in AutoDock 1.5.7.Furthermore,and violin plot and gene set enrichment analysis were performed to explore the role of hub genes in damp-heat internalized T2D.Finally,the interactions of hub compound and genes were explored using Comparative Toxicogenomics Database and quantitative polymerase chain reaction.Results:First,herb-compounds-genes-disease network illustrated that the hub compound of EZECD for damp-heat internalized T2D could be quercetin.Consistently,the hub genes were CASP8,CCL2,and AHR according to weighted gene co-expression network analysis.Molecular docking showed that quercetin could bind with the hub genes.Further,gene set enrichment analysis and Gene Ontology represented that CASP8,or CCL2,is negatively involved in insulin secretion response to the TNF or lipopolysaccharide process,and AHR or CCL2 positively regulated lipid and atherosclerosis,and/or including NOD-like receptor signaling pathway,and TNF signaling pathway.Ultimately,the quantitative polymerase chain reaction and western blotting analysis showed that quercetin could down-regulated the mRNA and protein experssion of CASP8,CCL2,and AHR.It was consistent with the results in Comparative Toxicogenomics Database databases.Conclusion:These results demonstrated quercetin could inhibit the expression of CASP8,CCL2,AHR in damp-heat internalized T2D,which improves insulin secretion and inhibits lipid and atherosclerosis,as well as/or including NOD-like receptor signaling pathway,and TNF signaling pathway,suggesting that EZECD may be more effective to treat damp-heat internalized T2D.
基金Guangxi Key R&D Program Project(GuiKe AB18221095)National and Autonomous Region-Level College Student Innovation and Entrepreneurship Training Funding Project(202210599009)High-level Talent Research Project of Youjiang Medical University for Nationalities(01002018079).
文摘[Objectives]To explore the mechanism of Gegen Qinlian Decoction in treating type 2 diabetes mellitus(T2DM)complicated with non-alcoholic fatty liver disease(NAFLD)by analyzing the effective components of Gegen Qinlian Decoction.[Methods]TCMSP database was used to analyze the active components of Gegen Qinlian Decoction,and pubchem and Swiss ADME databases were also used to predict drug targets,extract T2DM complicated with NAFLD targets from OMIM and Genecards databases.Venny plot was drawn to obtain intersection targets,and finally Cytoscape was used to make core target maps and drug-target-disease network maps.Using DAVID and Metascape database to analyze the intersection targets,the gene ontology information of Go and KEGG was obtained.Microbial informatics technology was used to visualize GO,and Cytoscape was used to make drug-target-disease network map-enrichment pathway map.[Results]The network pharmacological analysis showed that Gegen Qinlian Decoction acted on the key targets of type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease,such as ALB and ALT1,through many components,and achieved the purpose of treating this disease.The chemical constituents of the drug include formononetin,5-hydroxyisomucronulatol-2,5-2-O-glucoside,cholesteryl laurate,isoliquiritigenin,etc.[Conclusions]This study provides a new idea and theoretical support for future drug research and clinical practice.
基金supported by the Xiamen High-Level Health Talents Introduction and Training Project(Xiaweidang 2021-124)the National Natural Science Foundation of China(No.81774319).
文摘Background:The development and prognosis of breast cancer are intricately linked to psychological stress.In addition,depression is the most common psychological comorbidity among breast cancer survivors,and reportedly,Fang-Xia-Dihuang decoction(FXDH)can effectively manage depression in such patients.However,its pharmacological and molecular mechanisms remain obscure.Methods:Public databases were used for obtaining active components and related targets.Main active components were further verified by ultra-high-performance liquid chromatography-high-resolution mass spectrometry(UPLC-HRMS).Protein–protein interaction and enrichment analyses were taken to predict potential hub targets and related pathways.Molecule docking was used to understand the interactions between main compounds and hub targets.In addition,an animal model of breast cancer combined with depression was established to evaluate the intervention effect of FXDH and verify the pathways screened by network pharmacology.Results:174 active components of FXDH and 163 intersection targets of FXDH,breast cancer,and depression were identified.Quercetin,methyl ferulate,luteolin,ferulaldehyde,wogonin,and diincarvilone were identified as the principal active components of FXDH.Protein–protein interaction and KEGG enrichment analyses revealed that the phosphoinositide-3-kinase–protein kinase B(PI3K/AKT)and Janus kinase/signal transducer and activator of transcription(JAK2/STAT3)signaling pathways played a crucial role in mediating the efficacy of FXDH for inhibiting breast cancer progression induced by depression.In addition,in vivo experiments revealed that FXDH ameliorated depression-like behavior in mice and inhibited excessive tumor growth in mice with breast cancer and depression.FXDH treatment downregulated the expression of epinephrine,PI3K,AKT,STAT3,and JAK2 compared with the control treatment(p<0.05).Molecular docking verified the relationship between the six primary components of FXDH and the three most important targets,including phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA),AKT,and STAT3.Conclusion:This study provides a scientific basis to support the clinical application of FXDH for improving depression-like behavior and inhibiting breast cancer progression promoted by chronic stress.The therapeutic effects FXDH may be closely related to the PI3K/AKT and JAK2/STAT3 pathways.This finding helps better understand the regulatory mechanisms underlying the efficacy of FXDH.
基金the Construction Project of Workshop of Prestigious Chinese Physician Xiu-Hai Su(2022-75).
文摘Background:This study will be aimed at investigating the effects of Baihu Renshen decoction(BHRS)on type 2 diabetes rats and on macromolecular enzyme 1(PINK1)/E3 ubiquitin protein ligase(Parkin)pathway.Methods:The experiment was divided into four groups:control group,model group,metformin group and BHRS low-dose group and high-dose group.Forty male rats were selected as samples and randomly assigned to at least one test group.Finally,there are 18 rats in each group.Except for the control group,the rats within the different teams got a high-fat diet associate in nursing an intraperitoneal injection of streptozotocin to make a type 2 diabetes mellitus(T2DM)rat model.The organic chemistry and inflammatory indexes of rats in every cluster were analyzed and compared once four weeks of intragastric administration of comparable reagents to review the therapeutic impact of BHRS on T2DM.In addition,we determined the pathological changes of ductal gland tissue of T2DM rats after treatment,and compared the expression of mitochondrial phagocytosis related proteins in ductal gland tissue of rats in each group.Results:FBG,LDL-C,TC,TG,MDA,IL-1,IL-6,TNF-,and mitophagy-related proteins COXIV,P62,VDAC1,and TOM20 were elevated in the model group compared to the control group,while HDL-C,SOD,GSH-Px,and mitophagy-related proteins PINK1,Parkin,and LC3II/I were decreased(P<0.05 or P<0.01).The expressions of FBG,TC,TG,LDL-C,MDA,IL-1,IL-6,TNF-,and mitophagy-related proteins COXIV,P62,VDAC1,and TOM20 were lowered in the BHRS group,while the expressions of HOMA-,HDL-C,SOD,GSH-Px,and mitophagy-related proteins PINK1,Parkin,and LC3II/I were(P<0.05 or P<0.01).After therapy with BHRS,hematoxylin-eosin staining showed that the intensity of pancreatic acinar staining increased,and islet cells became clear boundaries that were,regularly arranged,and with reduced vacuoles reduced.Conclusion:BHRS has a clear therapeutic effect on T2DM,which may be achieved by regulating mitochondrial autophagy through the PINK1/Parkin pathway.
基金Scientific Research Project of Heilongjiang Provincial Health Commission(No.20222121020595)Traditional Chinese Medicine Research Project of Heilongjiang Province(No.ZHY2020-041)。
文摘Objective:To observe the effect of Qishen decoction on macrophage polarization mediated by miR-495/FTO signaling pathway,and to clarify the molecular mechanism of Qishen decoction in improving insulin resistance in the treatment of type 2 diabetes.Methods:THP-1 was induced to differentiate macrophages with phorbol ester.It was divided into the control group,the model group,the Qishen decoction group,the miR-495 inhibitor group,and the Qishen decoction+miR-495 inhibitor group.Except for the control group,the remaining groups were stimulated with 30 mmol/L glucose to construct a macrophage polarization model,and corresponding drugs were given for intervention.Cells were collected from each group for 24 hours and the content of inflammatory factors(IL-6,IL-1β,IL-4,and IL-10)were detected using enzyme-linked immunosorbent assay.The expression of macrophage polarization marker molecules,miR-495,and FTO were detected by flow cytometry,qPCR,and Western blot to detect.Results:Compared with the control group,there was no significant change in the activity of macrophages in the control serum,Qishen decoction containing serum,and miR-495 inhibitor transfected serum,and the difference was not statistically significant(P>0.05).In addition,compared to the control group,the content of IL-6 and IL-1β,the expression levels of CD68,iNOS,COX-2,miR-495,and the ratio of CD68/CD206,were significantly increased(P<0.01).While the content of IL-4 and IL-10,as well as the expression of CD206,Arg-1,YM-1,and FTO were significantly reduced(P<0.01).Compared with the model group,the QiShen decoction significantly reduced the contents of IL-6 and IL-1β,and the expression levels of CD68,iNOS,COX-2,and miR-495,as well as the ratio of CD68/CD206,while the content of IL-4 and IL-10,as well as the expression of CD206,Arg-1,YM-1,and FTO were significantly increased(P<0.01).Conclusion:Qishen decoction upregulate the expression of FTO to promote M2 type polarization of macrophages,thereby inhibiting inflammation and improving insulin resistance by inhibiting the expression of miR-495.
文摘目的探讨胃衡汤调控核因子E2相关因子2(Nrf2)-Kelch样环氧氯丙烷相关蛋白(Keap)信号通路抑制老年胃癌前病变(Precancerous lesions of gastric cancer,PLGC)患者氧化应激反应的作用。方法选取2022年3月-2023年3月期间于南京中医药大学第二附属医院消化腔镜中心和脾胃病科就诊的PLGC老年患者60例,按随机数字表法分为基础治疗组与胃衡汤治疗组,每组各30例。另选择同期常规胃镜体检的慢性浅表性胃炎患者30例为对照组。对照组仅入组接受研究相关指标检测,不予治疗。基础治疗组患者给予雷贝拉唑钠肠溶胶囊,胃衡汤组在基础治疗组上加用胃衡汤治疗,均治疗6个月。观察比较两组PLGC患者临床疗效、安全性,治疗前后中医证候评分、胃镜病理分级及Nrf2-Keap通路相关蛋白检测。结果治疗后胃衡汤治疗组中医证候疗效总有效率93.33%(28/30)明显高于基础治疗组76.67%(23/30),差异有统计学意义(P<0.05)。治疗后胃衡汤治疗组病理组织学疗效总有效率83.33%(25/30)明显高于基础治疗组63.33%(19/30),差异有统计学意义(P<0.05)。治疗后两组患者中医证候各项积分及总积分均较治疗前降低,差异有统计学意义(P<0.05);且胃衡汤治疗组中医证候各项积分及总积分均明显低于基础治疗组,差异有统计学意义(P<0.05)。治疗后两组患者胃黏膜组织学各项积分及总分均较治疗前降低,差异有统计学意义(P<0.05);且胃衡汤治疗组胃黏膜组织学各项积分及总分均明显低于基础治疗组,差异有统计学意义(P<0.05)。治疗后两组患者Nrf2和SOD表达高于治疗前,Keap1和MDA表达较治疗前降低,差异有统计学意义(P<0.05);且胃衡汤治疗组Nrf2和SOD表达明显高于基础治疗组,Keap1和MDA表达明显低于基础治疗组,差异有统计学意义(P<0.05)。治疗期间,两组患者治疗前后肝肾功能、三大常规及心电图检查均未发现异常。结论胃衡汤治疗老年PLGC能够改善临床症状,抑制甚至逆转病理学改变,提高治疗效果,其机制与调节Nrf2-Keap信号通路而抑制氧化应激反应有关。
基金sponsored by GraduateStudent Research and Innovation Program of Jiangsu Province,No.CX09B_267Z
文摘In the present study, a human neuroblastoma cell line （SH-SY5Y） and BV-2 microglia were treated with amyloid-β peptide （25-35）, as a model of Alzheimer＇s disease, to evaluate the protective effects of 10-3-10-8 g/mL Lingguizhugan decoction and to examine the underlying anti-inflammatory mechanism. Lingguizhugan decoction significantly enhanced the viability of SH-SY5Y cells with amyloid-β peptide-induced injury, and lowered levels of interleukin-1β, interleukin-6, tumor necrosis factor-a and nitric oxide in the culture supernatant of activated BV-2 microglia. The effects of 103 g/mL Lingguizhugan decoction were more significant. These results suggest that Lingguizhugan decoction can protect SH-SY5Y cells against amyloid-β peptide （25-35）-induced injury in a dose-dependent manner by inhibiting overexpression of inflammatory factors by activated microglia.
基金supported by grants from the National Natural Science Foundation of China(No.81102692)the Natural Science Foundation of Hubei Province,China(No.JX6B09)the Fundamental Research Funds for the Central Universities,China(No.2015QN203)
文摘Summary： In order to investigate whether Yinchenhao decoction （YCHD） attenuates hepatic fibro- genesis in the bile duct ligation （BDL） model via recovering and restoring the self-regulation and bal- ance of the renin-angiotensin system （RAS）, 33 specific-pathogen-free （SPF） male Sprague-Dawley rats with common BDL and scission were randomly divided into five groups as follows： G1, the sham group （n=4）; G2, BDL 7-day group （n=5）; G3, BDL＋YCHD 430 mg/mL （n=8）; G4, BDL＋losartan 0.65 mg/mL （ARB group, n=8）; G5, model group （BDL without any treatment, n=8）. YCHD and losartan （10 mL.kgl.day-1） were given by gastric gavage for 16 days following BDL in G3 and G4 groups, respec- tively. The effect of YCHD on liver fibrosis and the detailed molecular mechanisms were assessed by liver function including total bilirubin （TBIL）, direct bilirubin （DBIL）, indirect bilirubin （IDBIL）, alanine aminotransferase （ALT）, and aspartate aminotransferase （AST）. Histological changes were ob-. served by transmission electron microscopy （TEM） and Masson trichrome staining. Western blotting was used to detect the protein expression level of the renin-angiotensin system （RAS） components in- cluding angiotensin converting enzyme （ACE）, angiotensin II type 1 receptor （AT1R）, ACE2, angio- tensin II （Ang II） as well as transforming growth factor 131 （TGF131）. The experimental data were ana- lyzed by principle component analytical method of pattern recognition. The results showed that bio- chemically, serum TBIL, DBIL, IDBIL, ALT and AST levels were markedly increased following BDL as compared with the sham group （P〈0.05）. Serum TBIL, IDBIL and DBIL levels in G3 group were dramatically decreased as compared with G5 and G4 groups （P〈0.05）. Serum AST level in G3 was sig- nificantly lowered than in G5 group （P〈0.05）, but there was no significant difference in ALT among G3, G4 and G5 groups （P〉0.05）. Histologically, livers in G3 group showed less hepatocytes necrosis, less bile duct hyperplasia and less collagen formation than in G4 and G5 groups. The protein expression lev- els of ACE2, ACE, Ang II, AT1R and TGF131 in G2, G3 and G4 groups were significantly higher than in sham group （P〈0.05）, and lower than in G5 group （P〈0.05）. However, the differences among G2, G3 and G4 groups were not significant （P〉0.05）. ACE2 protein expression in G3 group was significantly higher than in G2 group （P〈0.05） and there was no significant difference in comparison with G4 group （P〉0.05）. Moreover, the protein expression of TGF131 in G3 group was significantly lower than in G5 and G4 groups （P〈0.05）. Our findings suggest that the antifibrotic effects of YCHD may be associated with the decreased classical RAS pathway components and TGFI31 downexpression so as to recover and rebuild self-regulation of the RAS by elevating the protein expression of ACE2.
