BACKGROUND Patients with diabetes mellitus are at higher risk of myocardial ischemia/reperfusion injury(MI/RI).Shuxin decoction(SXT)is a proven recipe modification from the classic herbal formula"Wu-tou-chi-shi-z...BACKGROUND Patients with diabetes mellitus are at higher risk of myocardial ischemia/reperfusion injury(MI/RI).Shuxin decoction(SXT)is a proven recipe modification from the classic herbal formula"Wu-tou-chi-shi-zhi-wan"according to the traditional Chinese medicine theory.It has been successfully used to alleviate secondary MI/RI in patients with diabetes mellitus in the clinical setting.However,the underlying mechanism is still unclear.AIM To further determine the mechanism of SXT in attenuating MI/RI associated with diabetes.METHODS This paper presents an ensemble model combining network pharmacology and biology.The Traditional Chinese Medicine System Pharmacology Database was accessed to select key components and potential targets of the SXT.In parallel,therapeutic targets associated with MI/RI in patients with diabetes were screened from various databases including Gene Expression Omnibus,DisGeNet,Genecards,Drugbank,OMIM,and PharmGKB.The potential targets of SXT and the therapeutic targets related to MI/RI in patients with diabetes were intersected and subjected to bioinformatics analysis using the Database for Annotation,Visualization and Integrated Discovery.The major results of bioinformatics analysis were subsequently validated by animal experiments.RESULTS According to the hypothesis derived from bioinformatics analysis,SXT could possibly ameliorate lipid metabolism disorders and exert anti-apoptotic effects in MI/RI associated with diabetes by reducing oxidized low density lipoprotein(LDL)and inhibiting the advanced glycation end products(AGE)-receptor for AGE(RAGE)signaling pathway.Subsequent animal experiments confirmed the hypothesis.The treatment with a dose of SXT(2.8 g/kg/d)resulted in a reduction in oxidized LDL,AGEs,and RAGE,and regulated the level of blood lipids.Besides,the expression of apoptosis-related proteins such as Bax and cleaved caspase 3 was down-regulated,whereas Bcl-2 expression was up-regulated.The findings indicated that SXT could inhibit myocardial apoptosis and improve cardiac function in MI/RI in diabetic rats.CONCLUSION This study indicated the active components and underlying molecular therapeutic mechanisms of SXT in MI/RI with diabetes.Moreover,animal experiments verified that SXT could regulate the level of blood lipids,alleviate cardiomyocyte apoptosis,and improve cardiac function through the AGE-RAGE signaling pathway.展开更多
Objective:In order to explore the systematical regulatory mechanism of Kushen(Sophora flavescens,SF)on inflammation and cancer,we analyzed inter-molecular interactions between herbal ingredients of SF and human inflam...Objective:In order to explore the systematical regulatory mechanism of Kushen(Sophora flavescens,SF)on inflammation and cancer,we analyzed inter-molecular interactions between herbal ingredients of SF and human inflammation and cancer through network-pharmacology and molecular docking-based approaches.Methods:Firstly,ingredients and potential targets were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,GeneCards database,Therapeutic Targets Database and Online Mendelian Inheritance in Man database.Then,protein-protein interaction network and medicine-ingredient-target-disease network were established and analyzed via STRING and Cytoscape.Surflex-dock was performed by SybylX-2.0.Finally,functional enrichment and pathway enrichment were achieved by Gene Ontology database and Kyoto Encyclopedia of Genes and Genomes database.Results:The results showed that 113 components of SF and 53 potential targets were related in the study.SF exerts anti-inflammatory and anti-cancer mechanism through key targets located in nucleus,such as JUN,MYC,RELA,NCOA,PPARG which may trigger the NF-κB pathway,the Bcl-2/Bax pathway and other pathways to effect DNA transcriptional activity.Conclusions:The study predicted the mechanism of SF on cancer and inflammation.According to the results,we suggest that the ingredients of SF effect on DNA bingding and transcription in nuclear receptors-like JUN,MYC,RELA,NCOA,PPARG.the receptors trigger several pathways including NF-κB pathway,the Bcl-2/Bax pathway and others.Eventually,it regulats inflammatory factors and cell proliferation,senescence and apoptosis.展开更多
Aim Liver fibrosis is a consequence of chronic liver disease which can progress into liver cirrhosis evenhepatocarcinoma. FuzhengHuayu （FZHY） , a Chinese herbal formula, had been reported to have the effect of anti-...Aim Liver fibrosis is a consequence of chronic liver disease which can progress into liver cirrhosis evenhepatocarcinoma. FuzhengHuayu （FZHY） , a Chinese herbal formula, had been reported to have the effect of anti- fibrosis. This study aims to investigate the effective targets and the mechanisms of FZHY on liver fibrosis. Methods The liver tissue samples of normal group, model group and FZHY-treated group were examined by microarray and iTRAQ. Profiles of differentially expressed genes （DEGs） and differentially expressed proteins （DEPs） in CC14-in- duced liver fibrosis model in rat were analyzed. GO and Pathway were analyzed by DAVID, and protein-protein in- teraction （PPI） was analyzed by STRING and cytoscape. The targets of FZHY compounds were predicted by TCM- SP. Results The results showed that 255 genes （ fold change ≥ 1.5, P 〈 0.05） and 507 proteins （ fold change ≥ 1.2 ,P 〈 0.05 ） were differentially expressed between FZHY group and model group. The high-throughput data of transcriptomics and proteomics was analyzed synthetically. DAVID function annotation analysis showed that these DEGS and DEPs both enriched in 15 GO terms, among drug metabolic process, response to extracellular stimulus, response to vitamin, arachidonic acid metabolic process, response to wounding and oxidation reduction may involve in liver fibrosis. KEGG pathway analysis showed that these DEGS and DEPs both enriched in 9 pathways, among arachidonic acid metabolism, retinol metabolism, metabolism of xenobiotics by cytochrome P450 and drug metabo- lism may be related to liver fibrosis. PPI analysis found that 10 overlapped core genes and proteins, among, Ugt2a3, Cyp2bl and Cyp3al8 were of higher degree, which are all enriched in retinol metabolism. Interestedly, Cyp2bl and Cyp3al8 were also predicted with TCMSP as the targets of FZHY compounds. Conclusion The re- sults indicated that the effective mechanism of FZHY against liver fibrosis is involved in the regulation of multiple targets and multiple pathways, among, retinol metabolism pathway by targeting Ugt2a3, Cyp2bl and Cyp3al8 may play an important role in the treatment of liver fibrosis.展开更多
基金Supported by Natural Science Foundation of Sichuan Province,No.2022NSFSC0738Basic Research Funds for Central Universities,No.2682022ZTPY038Tibet Autonomous Region Science and Technology Planning Project,No.XZ2022RH001.
文摘BACKGROUND Patients with diabetes mellitus are at higher risk of myocardial ischemia/reperfusion injury(MI/RI).Shuxin decoction(SXT)is a proven recipe modification from the classic herbal formula"Wu-tou-chi-shi-zhi-wan"according to the traditional Chinese medicine theory.It has been successfully used to alleviate secondary MI/RI in patients with diabetes mellitus in the clinical setting.However,the underlying mechanism is still unclear.AIM To further determine the mechanism of SXT in attenuating MI/RI associated with diabetes.METHODS This paper presents an ensemble model combining network pharmacology and biology.The Traditional Chinese Medicine System Pharmacology Database was accessed to select key components and potential targets of the SXT.In parallel,therapeutic targets associated with MI/RI in patients with diabetes were screened from various databases including Gene Expression Omnibus,DisGeNet,Genecards,Drugbank,OMIM,and PharmGKB.The potential targets of SXT and the therapeutic targets related to MI/RI in patients with diabetes were intersected and subjected to bioinformatics analysis using the Database for Annotation,Visualization and Integrated Discovery.The major results of bioinformatics analysis were subsequently validated by animal experiments.RESULTS According to the hypothesis derived from bioinformatics analysis,SXT could possibly ameliorate lipid metabolism disorders and exert anti-apoptotic effects in MI/RI associated with diabetes by reducing oxidized low density lipoprotein(LDL)and inhibiting the advanced glycation end products(AGE)-receptor for AGE(RAGE)signaling pathway.Subsequent animal experiments confirmed the hypothesis.The treatment with a dose of SXT(2.8 g/kg/d)resulted in a reduction in oxidized LDL,AGEs,and RAGE,and regulated the level of blood lipids.Besides,the expression of apoptosis-related proteins such as Bax and cleaved caspase 3 was down-regulated,whereas Bcl-2 expression was up-regulated.The findings indicated that SXT could inhibit myocardial apoptosis and improve cardiac function in MI/RI in diabetic rats.CONCLUSION This study indicated the active components and underlying molecular therapeutic mechanisms of SXT in MI/RI with diabetes.Moreover,animal experiments verified that SXT could regulate the level of blood lipids,alleviate cardiomyocyte apoptosis,and improve cardiac function through the AGE-RAGE signaling pathway.
基金This work was supported by the National Natural Science Foundation of China(81402801,81973544,81803790)the Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme(GDHVPS2018)the Young Elite Scientists Sponsorship Program by CACM(2019-QNRC2-C14).
文摘Objective:In order to explore the systematical regulatory mechanism of Kushen(Sophora flavescens,SF)on inflammation and cancer,we analyzed inter-molecular interactions between herbal ingredients of SF and human inflammation and cancer through network-pharmacology and molecular docking-based approaches.Methods:Firstly,ingredients and potential targets were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,GeneCards database,Therapeutic Targets Database and Online Mendelian Inheritance in Man database.Then,protein-protein interaction network and medicine-ingredient-target-disease network were established and analyzed via STRING and Cytoscape.Surflex-dock was performed by SybylX-2.0.Finally,functional enrichment and pathway enrichment were achieved by Gene Ontology database and Kyoto Encyclopedia of Genes and Genomes database.Results:The results showed that 113 components of SF and 53 potential targets were related in the study.SF exerts anti-inflammatory and anti-cancer mechanism through key targets located in nucleus,such as JUN,MYC,RELA,NCOA,PPARG which may trigger the NF-κB pathway,the Bcl-2/Bax pathway and other pathways to effect DNA transcriptional activity.Conclusions:The study predicted the mechanism of SF on cancer and inflammation.According to the results,we suggest that the ingredients of SF effect on DNA bingding and transcription in nuclear receptors-like JUN,MYC,RELA,NCOA,PPARG.the receptors trigger several pathways including NF-κB pathway,the Bcl-2/Bax pathway and others.Eventually,it regulats inflammatory factors and cell proliferation,senescence and apoptosis.
文摘Aim Liver fibrosis is a consequence of chronic liver disease which can progress into liver cirrhosis evenhepatocarcinoma. FuzhengHuayu （FZHY） , a Chinese herbal formula, had been reported to have the effect of anti- fibrosis. This study aims to investigate the effective targets and the mechanisms of FZHY on liver fibrosis. Methods The liver tissue samples of normal group, model group and FZHY-treated group were examined by microarray and iTRAQ. Profiles of differentially expressed genes （DEGs） and differentially expressed proteins （DEPs） in CC14-in- duced liver fibrosis model in rat were analyzed. GO and Pathway were analyzed by DAVID, and protein-protein in- teraction （PPI） was analyzed by STRING and cytoscape. The targets of FZHY compounds were predicted by TCM- SP. Results The results showed that 255 genes （ fold change ≥ 1.5, P 〈 0.05） and 507 proteins （ fold change ≥ 1.2 ,P 〈 0.05 ） were differentially expressed between FZHY group and model group. The high-throughput data of transcriptomics and proteomics was analyzed synthetically. DAVID function annotation analysis showed that these DEGS and DEPs both enriched in 15 GO terms, among drug metabolic process, response to extracellular stimulus, response to vitamin, arachidonic acid metabolic process, response to wounding and oxidation reduction may involve in liver fibrosis. KEGG pathway analysis showed that these DEGS and DEPs both enriched in 9 pathways, among arachidonic acid metabolism, retinol metabolism, metabolism of xenobiotics by cytochrome P450 and drug metabo- lism may be related to liver fibrosis. PPI analysis found that 10 overlapped core genes and proteins, among, Ugt2a3, Cyp2bl and Cyp3al8 were of higher degree, which are all enriched in retinol metabolism. Interestedly, Cyp2bl and Cyp3al8 were also predicted with TCMSP as the targets of FZHY compounds. Conclusion The re- sults indicated that the effective mechanism of FZHY against liver fibrosis is involved in the regulation of multiple targets and multiple pathways, among, retinol metabolism pathway by targeting Ugt2a3, Cyp2bl and Cyp3al8 may play an important role in the treatment of liver fibrosis.
