Background:To explore the mechanism of action of Zhishi Daozhi decoction in treating diarrhea using network pharmacology and molecular docking.Methods:The pharmacological components and targets of Zhishi Daozhi decoct...Background:To explore the mechanism of action of Zhishi Daozhi decoction in treating diarrhea using network pharmacology and molecular docking.Methods:The pharmacological components and targets of Zhishi Daozhi decoction were searched by The TCMSP and Uniprot database and the disease genes of diarrhea were obtained from GeneCard and diagenetic databases.The network software venny 2.1.0 was used to screen the intersection targets of Zhishi Daozhi decoction in treating diarrhea.STRING database was used to construct protein interaction network,Metascape database analysis platform for gene ontology enrichment and Kyoto Gene and Genome Encyclopedia pathway enrichment analysis.Using Cytoscape 3.9.1 software to map the“Chinese herbal medicine-active ingredient-target”network and perform network topology to identify the core genes.Selecting core genes and critical components for molecular docking.Results:203 active ingredients and 259 target genes were obtained from Zhishi Daozhi decoction,206 genes were cross-linked with the disease gene control after de-duplication,1001 entries meeting the screening criteria were obtained after gene ontology enrichment analysis,and 169 entries were obtained after Kyoto Gene and Genome Encyclopedia enrichment analysis,in which the biological processes were mainly enriched in the cellular responses to lipids,hormones,radiation,growth factors,and cell fractionation.The Kyoto Gene and Genome Encyclopedia pathway enrichment analysis suggested that it mainly covers the cancer pathway,hepatitis B,cellular senescence,IL-17 signaling pathway,PI3K-Akt signaling pathway,etc.The molecular docking results showed that the vital active ingredients,such as lignocaine and quercetin,with better binding activity to the vital core targets,such as MMP3,AKT1,and CCL2.Conclusion:The active ingredients such as quercetin and luteolin in Zhishi Daozhi decoction may act through signaling pathways such as IL-17 signaling pathway,PI3K-Akt signaling pathway,TGF-βsignaling pathway,and other pathways,and act on the critical core targets such as MMP3,AKT1,HSP90AA1,FOS,CCL2,and TGFB1 to enhance intestinal barrier function,reduce the inflammatory response and regulate intestinal flora,thus achieving the purpose of treating diarrhea.展开更多
目的分析加味枳实薤白桂枝汤对肥胖症(脾虚湿阻型)合并2型糖尿病患者糖脂代谢指标的影响。方法选择160例肥胖症(脾虚湿阻型)同时合并2型糖尿病的患者,随机分为试验组(81例)与对照组(79例)。对照组予以规范生活指导及规范的降糖药物干预...目的分析加味枳实薤白桂枝汤对肥胖症(脾虚湿阻型)合并2型糖尿病患者糖脂代谢指标的影响。方法选择160例肥胖症(脾虚湿阻型)同时合并2型糖尿病的患者,随机分为试验组(81例)与对照组(79例)。对照组予以规范生活指导及规范的降糖药物干预,试验组在对照组治疗基础上给予加味枳实薤白桂枝汤口服,疗程共2个月,比较两组治疗前后中医证候积分、低密度脂蛋白胆固醇(LDL-C)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、三酰甘油(TG)、空腹血糖(FPG)、餐后2 h血糖(2 h FPG)、糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)、尿酸(UA)、体重指数(BMI)、同型半胱氨酸(Hcy)水平。结果治疗后,试验组中医证候积分、BMI、UA、Hcy、TG、LDL-C、FPG、HbA1c、2 h FPG、FINS水平显著低于对照组(P<0.05)。结论加味枳实薤白桂枝汤可以调节肥胖症合并2型糖尿病该类型患者的糖脂代谢指标。展开更多
目的探究白虎人参汤合枳实薤白桂枝汤对糖尿病心肌病模型MKR小鼠心肌细胞焦亡相关蛋白表达的影响。方法造模成功后将MKR小鼠随机分成模型组,中药低、中、高剂量组,二甲双胍组,同时设FVB鼠为正常组。给药4周后观察小鼠糖脂代谢变化;超声...目的探究白虎人参汤合枳实薤白桂枝汤对糖尿病心肌病模型MKR小鼠心肌细胞焦亡相关蛋白表达的影响。方法造模成功后将MKR小鼠随机分成模型组,中药低、中、高剂量组,二甲双胍组,同时设FVB鼠为正常组。给药4周后观察小鼠糖脂代谢变化;超声成像平台检测小鼠心功能;HE染色及MASSON染色观察心肌组织形态;ELISA法测定血清中白细胞介素-18(interleukin-18,IL-18)、白细胞介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平;Western blot法检测小鼠心肌组织NOD样受体蛋白3(nucleotidebinding oligomerization domain-like receptors 3,NLRP3)、凋亡相关斑点样蛋白(apoptosis-associated speck-like protein contain a CARD,ASC)、半胱氨酸的天冬氨酸蛋白水解酶-1(cysteinyl aspartate specific proteinase-1,Caspase-1)蛋白水平。结果与正常组比较,模型组小鼠空腹血糖(fasting blood glucose,FBG)显著升高(P<0.01),血清总胆固醇(serum total cholesterol,TC)、甘油三酯(triglyceride,TG)、低密度脂蛋白(low density lipoprotein,LDL)水平升高(P<0.05),高密度脂蛋白胆固醇(high density liptein cholesterol,HDL-C)水平降低(P<0.05),左室射血分数(rejection fraction,EF)、左室短轴缩短率(fractional shortening,FS)数值明显降低(P<0.01);细胞肥大变形,心肌纤维排列紊乱,纹理不齐,血清IL-1β、IL-18、TNF-α含量升高(P<0.01),心肌组织IL-1β、IL-18、TNF-α蛋白表达水平提升(P<0.01),心肌组织NLRP3、ASC、Caspase-1蛋白表达均显著增高(P<0.01)。与模型组比较,各用药组小鼠FBG、TC、TG、LDL水平降低(P<0.05),HDL-C水平升高(P<0.05),EF、FS值均有升高(P<0.05),小鼠心肌组织病理学损伤明显改善,血清IL-1β、IL-18、TNF-α含量降低(P<0.05),NLRP3、ASC、Caspase-1蛋白表达均明显降低(P<0.05),其中中药高剂量组作用最为明显。结论白虎人参汤合枳实薤白桂枝汤对心肌有保护作用,其机制可能与抑制NLRP3炎症小体过度激活,减少心肌细胞焦亡,降低炎症反应有关。展开更多
Background:Four classical Traditional Chinese Medicine prescriptions,namely Gualou Xiebai Baijiu decoction,Gualou Xiebai Banxia decoction(GLXBBX),Zhishi Xiebai Guizhi decoction(ZSXBGZ)and Danlou prescription(DL),have ...Background:Four classical Traditional Chinese Medicine prescriptions,namely Gualou Xiebai Baijiu decoction,Gualou Xiebai Banxia decoction(GLXBBX),Zhishi Xiebai Guizhi decoction(ZSXBGZ)and Danlou prescription(DL),have been frequently used for treatment of phlegm and blood stasis syndrome(PBSS)-related cardiovascular diseases.However,its therapeutic mechanism has not been clearly elucidated.This study aimed to explore PBSS and its molecular mechanism,clarify and compare the mechanisms of four prescriptions in treating PBSS-related diseases.Method:In this study,we collected four prescriptions’compounds,predicted therapeutic targets,and enriched pathways which were based on network pharmacology.Then,we analysed the commen and different mechanisms by combing the network of components,targets and pathways.Finally,molecular docking was engaged to assess the binding potential of key compounds and hub targets.Results:We showed that four prescriptions’intersection genes(VEGFA,SRC,EGFR,etc.)were commonly enriched in PI3K-AKT signaling pathway,HIF-1 signaling pathway,etc.In addition,platelet activation and cAMP signaling pathway were singly enriched from the GLXBBX through unique compounds 12,13-epoxy-9-hydroxynonadeca-7,10-dienoic acid and Cyclo(L-tyrosyl-L-phenylalanyl).These bioactive compounds may exert GLXBBX’s unique pharmacological pathways via involving in mediating PPARA,PTGER3,etc.Sphingolipid signaling pathway was singly enriched from the ZSXBGZ through unique compounds tetramethoxyluteolin,ergosterol peroxide,etc.These bioactive compounds could mediate ADORA1,ADORA3 and TNFRSF1A to regulate ZSXBGZ’s unique pharmacological pathways.AMPK signaling pathway was singly enriched from the DL through unique compounds kaempferol,evofolinb,ethyl acid and aureusidin.These bioactive compounds were involved in mediating the main targets of AMPK signaling pathway,such as TNF,TNFRSF1A,etc.Conclusions:Our research demonstrated that GLXB-prescriptions involved in almost all pathological stages of PBSS-related cardiovascular diseases by modulating high-frequency shared pathways and targets mainly through key compounds(quercetin,mandenol,sitosteryl acetate and luteolin,etc.),for example,participate in the process of atherosclerosis,lipid metabolism,inflammation,immune response,thrombosis,inhibit inflammatory factors and platelet aggregation,regulate immune function,vascular function,oxidative stress.In addition to common pharmacological efficacies,there could also be specificities among GLXB prescriptions due to different compounds.For example,GLXBBX tends to regulate the function of vascular and endothelial barrier,prevent thrombosis.ZSXBGZ tends to regulate lipid metabolism and protect the heart from lipid accumulation.DL tends to maintain energy homeostasis and improve inflammation.展开更多
基金supported by the science and technology innovation particular topic of Maoming City(No.2021S0047)science and technology innovation particular topic of Maoming City(No.2022S0014).
文摘Background:To explore the mechanism of action of Zhishi Daozhi decoction in treating diarrhea using network pharmacology and molecular docking.Methods:The pharmacological components and targets of Zhishi Daozhi decoction were searched by The TCMSP and Uniprot database and the disease genes of diarrhea were obtained from GeneCard and diagenetic databases.The network software venny 2.1.0 was used to screen the intersection targets of Zhishi Daozhi decoction in treating diarrhea.STRING database was used to construct protein interaction network,Metascape database analysis platform for gene ontology enrichment and Kyoto Gene and Genome Encyclopedia pathway enrichment analysis.Using Cytoscape 3.9.1 software to map the“Chinese herbal medicine-active ingredient-target”network and perform network topology to identify the core genes.Selecting core genes and critical components for molecular docking.Results:203 active ingredients and 259 target genes were obtained from Zhishi Daozhi decoction,206 genes were cross-linked with the disease gene control after de-duplication,1001 entries meeting the screening criteria were obtained after gene ontology enrichment analysis,and 169 entries were obtained after Kyoto Gene and Genome Encyclopedia enrichment analysis,in which the biological processes were mainly enriched in the cellular responses to lipids,hormones,radiation,growth factors,and cell fractionation.The Kyoto Gene and Genome Encyclopedia pathway enrichment analysis suggested that it mainly covers the cancer pathway,hepatitis B,cellular senescence,IL-17 signaling pathway,PI3K-Akt signaling pathway,etc.The molecular docking results showed that the vital active ingredients,such as lignocaine and quercetin,with better binding activity to the vital core targets,such as MMP3,AKT1,and CCL2.Conclusion:The active ingredients such as quercetin and luteolin in Zhishi Daozhi decoction may act through signaling pathways such as IL-17 signaling pathway,PI3K-Akt signaling pathway,TGF-βsignaling pathway,and other pathways,and act on the critical core targets such as MMP3,AKT1,HSP90AA1,FOS,CCL2,and TGFB1 to enhance intestinal barrier function,reduce the inflammatory response and regulate intestinal flora,thus achieving the purpose of treating diarrhea.
文摘目的分析加味枳实薤白桂枝汤对肥胖症(脾虚湿阻型)合并2型糖尿病患者糖脂代谢指标的影响。方法选择160例肥胖症(脾虚湿阻型)同时合并2型糖尿病的患者,随机分为试验组(81例)与对照组(79例)。对照组予以规范生活指导及规范的降糖药物干预,试验组在对照组治疗基础上给予加味枳实薤白桂枝汤口服,疗程共2个月,比较两组治疗前后中医证候积分、低密度脂蛋白胆固醇(LDL-C)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、三酰甘油(TG)、空腹血糖(FPG)、餐后2 h血糖(2 h FPG)、糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)、尿酸(UA)、体重指数(BMI)、同型半胱氨酸(Hcy)水平。结果治疗后,试验组中医证候积分、BMI、UA、Hcy、TG、LDL-C、FPG、HbA1c、2 h FPG、FINS水平显著低于对照组(P<0.05)。结论加味枳实薤白桂枝汤可以调节肥胖症合并2型糖尿病该类型患者的糖脂代谢指标。
文摘目的探究白虎人参汤合枳实薤白桂枝汤对糖尿病心肌病模型MKR小鼠心肌细胞焦亡相关蛋白表达的影响。方法造模成功后将MKR小鼠随机分成模型组,中药低、中、高剂量组,二甲双胍组,同时设FVB鼠为正常组。给药4周后观察小鼠糖脂代谢变化;超声成像平台检测小鼠心功能;HE染色及MASSON染色观察心肌组织形态;ELISA法测定血清中白细胞介素-18(interleukin-18,IL-18)、白细胞介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平;Western blot法检测小鼠心肌组织NOD样受体蛋白3(nucleotidebinding oligomerization domain-like receptors 3,NLRP3)、凋亡相关斑点样蛋白(apoptosis-associated speck-like protein contain a CARD,ASC)、半胱氨酸的天冬氨酸蛋白水解酶-1(cysteinyl aspartate specific proteinase-1,Caspase-1)蛋白水平。结果与正常组比较,模型组小鼠空腹血糖(fasting blood glucose,FBG)显著升高(P<0.01),血清总胆固醇(serum total cholesterol,TC)、甘油三酯(triglyceride,TG)、低密度脂蛋白(low density lipoprotein,LDL)水平升高(P<0.05),高密度脂蛋白胆固醇(high density liptein cholesterol,HDL-C)水平降低(P<0.05),左室射血分数(rejection fraction,EF)、左室短轴缩短率(fractional shortening,FS)数值明显降低(P<0.01);细胞肥大变形,心肌纤维排列紊乱,纹理不齐,血清IL-1β、IL-18、TNF-α含量升高(P<0.01),心肌组织IL-1β、IL-18、TNF-α蛋白表达水平提升(P<0.01),心肌组织NLRP3、ASC、Caspase-1蛋白表达均显著增高(P<0.01)。与模型组比较,各用药组小鼠FBG、TC、TG、LDL水平降低(P<0.05),HDL-C水平升高(P<0.05),EF、FS值均有升高(P<0.05),小鼠心肌组织病理学损伤明显改善,血清IL-1β、IL-18、TNF-α含量降低(P<0.05),NLRP3、ASC、Caspase-1蛋白表达均明显降低(P<0.05),其中中药高剂量组作用最为明显。结论白虎人参汤合枳实薤白桂枝汤对心肌有保护作用,其机制可能与抑制NLRP3炎症小体过度激活,减少心肌细胞焦亡,降低炎症反应有关。
基金supportes by National Natural Science Foundation of China(Grant no.82274137,81873038)Natural Science Foundation of Anhui Province(2208085MH275)+2 种基金Natural Science Research Project of Anhui Provincial Department of Education(KJ2021A0592)Anhui University Scientific Research Project(YJS20210488)the 7th China International College Studengts“Internet+”Innovation and entrepreneurship Competition(S202110369046).
文摘Background:Four classical Traditional Chinese Medicine prescriptions,namely Gualou Xiebai Baijiu decoction,Gualou Xiebai Banxia decoction(GLXBBX),Zhishi Xiebai Guizhi decoction(ZSXBGZ)and Danlou prescription(DL),have been frequently used for treatment of phlegm and blood stasis syndrome(PBSS)-related cardiovascular diseases.However,its therapeutic mechanism has not been clearly elucidated.This study aimed to explore PBSS and its molecular mechanism,clarify and compare the mechanisms of four prescriptions in treating PBSS-related diseases.Method:In this study,we collected four prescriptions’compounds,predicted therapeutic targets,and enriched pathways which were based on network pharmacology.Then,we analysed the commen and different mechanisms by combing the network of components,targets and pathways.Finally,molecular docking was engaged to assess the binding potential of key compounds and hub targets.Results:We showed that four prescriptions’intersection genes(VEGFA,SRC,EGFR,etc.)were commonly enriched in PI3K-AKT signaling pathway,HIF-1 signaling pathway,etc.In addition,platelet activation and cAMP signaling pathway were singly enriched from the GLXBBX through unique compounds 12,13-epoxy-9-hydroxynonadeca-7,10-dienoic acid and Cyclo(L-tyrosyl-L-phenylalanyl).These bioactive compounds may exert GLXBBX’s unique pharmacological pathways via involving in mediating PPARA,PTGER3,etc.Sphingolipid signaling pathway was singly enriched from the ZSXBGZ through unique compounds tetramethoxyluteolin,ergosterol peroxide,etc.These bioactive compounds could mediate ADORA1,ADORA3 and TNFRSF1A to regulate ZSXBGZ’s unique pharmacological pathways.AMPK signaling pathway was singly enriched from the DL through unique compounds kaempferol,evofolinb,ethyl acid and aureusidin.These bioactive compounds were involved in mediating the main targets of AMPK signaling pathway,such as TNF,TNFRSF1A,etc.Conclusions:Our research demonstrated that GLXB-prescriptions involved in almost all pathological stages of PBSS-related cardiovascular diseases by modulating high-frequency shared pathways and targets mainly through key compounds(quercetin,mandenol,sitosteryl acetate and luteolin,etc.),for example,participate in the process of atherosclerosis,lipid metabolism,inflammation,immune response,thrombosis,inhibit inflammatory factors and platelet aggregation,regulate immune function,vascular function,oxidative stress.In addition to common pharmacological efficacies,there could also be specificities among GLXB prescriptions due to different compounds.For example,GLXBBX tends to regulate the function of vascular and endothelial barrier,prevent thrombosis.ZSXBGZ tends to regulate lipid metabolism and protect the heart from lipid accumulation.DL tends to maintain energy homeostasis and improve inflammation.