Background:According to traditional Chinese medicine(TCM),drugs supplementing the vital energy,Qi,can eliminate tumors by restoring host immunity.The objective of this study is to investigate the underlying immune mec...Background:According to traditional Chinese medicine(TCM),drugs supplementing the vital energy,Qi,can eliminate tumors by restoring host immunity.The objective of this study is to investigate the underlying immune mechanisms of anti-tumor activity associated with Qi-supplementing herbs,specifically the paired use of Huangqi and Danggui.Methods:Analysis of compatibility regularity was conducted to screen the combination of Qi-supplementing TCMs.Using the MTT assay and a transplanted tumor mice model,the anti-tumor effects of combination TCMs were investigated in vitro and in vivo.High content analysis and flow cytometry were then used to evaluate cellular immunity,followed by network pharmacology and molecular docking to dissect the significant active compounds and potential mechanisms.Finally,the anti-tumor activity and the mechanism of the active ingredients were verified by molecular experiments.Results:There is an optimal combination of Huangqi and Danggui that,administered as an aqueous extract,can activate immunity to suppress tumor and is more effective than each drug on its own in vitro and in vivo.Based on network pharmacology analysis,PIK3R1 is the core target for the anti-tumor immunity activity of combined Huangqi and Danggui.Molecular docking analysis shows 6 components of the combined Danggui and Huangqi extract(quercetin,jaranol,isorhamnetin,kaempferol,calycosin,and suchilactone)that bind to PIK3R1.Jaranol is the most important component against breast cancer.The suchilactone/jaranol combination and,especially,the suchilactone/kaempferol combination are key for immunity enhancement and the anti-tumor effects of the extract.Conclusions:The combination of Huangqi and Danggui can activate immunity to suppress breast cancer and is more effective than the individual drugs alone.展开更多
Objective:To observe the effects of Danggui Shaoyao powder(DSP)on hepatic lipid metabolism and further explore its mechanism of action by peroxisome proliferator-activated receptor(PPARγ)-liver X receptor(LXRα)-aden...Objective:To observe the effects of Danggui Shaoyao powder(DSP)on hepatic lipid metabolism and further explore its mechanism of action by peroxisome proliferator-activated receptor(PPARγ)-liver X receptor(LXRα)-adenosine triphosphate(ATP)-binding cassette transporter A1(ABCA1)pathway regulation.Methods: Eight C57BL/6J male mice were selected as the control group,and 24 ApoE^(−/−)male mice were randomly divided into the atherosclerosis model(AS)group,atorvastatin calcium(AC)group,and DSP group(n=8 each group).To establish an AS model,ApoE^(−/−)mice were fed a high-fat diet for 16 weeks.Pathologic changes in the aortic vasculature and liver were identified using Oil Red O staining.Triglyceride(TG),cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)levels were determined in the livers using a single-reagent GPO-PAP method.Fluorescence quantitative polymerase chain reaction and western blot were used to observe and evaluate the mRNA and protein expression of the PPARγ-LXRα-ABCA1 intermediates in the liver.Results: After 16 weeks of a high-fat diet,ApoE^(−/−)mice showed more Oil Red O staining in the aorta and liver compared to the CONT group.Compared to the AS group,the DSP and AC treatment reduced aortic plaque and hepatic lipid deposition to varying degrees.Furthermore,DSP significantly reduced the hepatic lipid area in ApoE^(−/−)mice(P<.001)and decreased the levels of TG,TC,and LDL-C in liver(P<.001,P=.027,P<.001,respectively).DSP also significantly increased the levels of PPARγ,LXRα,ABCA1,and ABCG1 mRNA expression,as well as the PPARγ,LXRα,ABCA1,and ABCG1 protein expression in liver.Conclusion: DSP improved hepatic lipid metabolism via PPARγ-LXRα-ABCA1 pathway modulation for AS treatment.展开更多
Chronic myeloid leukemia(CML)is a hematopoietic myeloproliferative disorder.The Chinese prescription Danggui Longhui Wan(DGLHW)has been utilized in CML treatment,but its underlying mechanisms remain unclear.In this st...Chronic myeloid leukemia(CML)is a hematopoietic myeloproliferative disorder.The Chinese prescription Danggui Longhui Wan(DGLHW)has been utilized in CML treatment,but its underlying mechanisms remain unclear.In this study,we gathered 794 constituents,1249 drug targets,1654 disease genes and 129 intersection genes.GO and KEGG were used to analyze the function of these genes.Compatibility of prescription study showed that monarch drug,minister drug,assistant and guide drug played a synergistic role in the treatment of CML.In addition,we obtained 20 hub genes and 12 key components.Molecular docking indicated that the main compounds and core proteins had good binding ability.The results of this study also showed that DGLHW might play a role in the treatment of CML by affecting MAPK,PI3K/AKT,FoxO and p53 signaling pathways.展开更多
Objective:Rheumatoid arthritis(RA)is a common autoimmune disease characterized by multiple joint lesions and systemic complications.Danggui Niantong decoction(DGNTT)has been clinically used for RA treatment;however,it...Objective:Rheumatoid arthritis(RA)is a common autoimmune disease characterized by multiple joint lesions and systemic complications.Danggui Niantong decoction(DGNTT)has been clinically used for RA treatment;however,its beneficial effect on cardiopulmonary complications has not been reported.Methods:Female tumor necrosis factor-transgenic(TNF-Tg)mice were used to evaluate the therapeutic effects of DGNTT on arthritis and cardiopulmonary complications.Methotrexate(MTX)served as a positive control.Histopathological assessment of the joint sections was performed using hematoxylin and eosin(HE),Alcian Blue/Orange G,and tartrate-resistant acid phosphatase staining.Bone mass was assessed by micro-computed tomography,inflammatory infiltrates in the heart and lungs were evaluated by HE staining,cardiopulmonary fibrotic injury was identified by Masson’s trichrome staining,and hypertrophy of mouse cardiomyocytes was measured by wheat germ agglutinin(WGA)staining.Results:DGNTT mitigated the inflammation of the ankle joint synovium,decreased the number of osteoclasts,and increased the area of cartilage and bone mass in TNF-Tg mice.In addition,DGNTT decreased the infiltration of inflammatory cells into the lung and heart tissues,accompanied by a reduction in cardiopulmonary fibrosis and myocardial cell hypertrophy in TNF-Tg mice.As a positive control drug,MTX attenuated the pathological changes in joints,but had no beneficial effect on cardiopulmonary inflammation and fibrosis in TNF-Tg mice.Conclusions:DGNTT improved joint lesions and alleviated cardiopulmonary complications in TNF-Tg mice.展开更多
Objective:To observe the effect of Jiawei Danggui Buxuetang on the expression of microRNA-155(miR-155)and cytokine signal transduction inhibitor 1(SOCS1)in renal tissue of rats with diabetic nephropathy(DKD),and to ex...Objective:To observe the effect of Jiawei Danggui Buxuetang on the expression of microRNA-155(miR-155)and cytokine signal transduction inhibitor 1(SOCS1)in renal tissue of rats with diabetic nephropathy(DKD),and to explore the mechanism of Jiawei Danggui Buxuetang in the treatment of DKD.Methods:Firty 6-week-old SPF male SD rats were randomly divided into normal group(CON)and model group.The model group was fed with high-sugar and high-fat diet for 6 weeks,and the DKD rat model was established by intraperitoneal injection of streptozotocin(STZ)(35 mg/kg).Then the rats were randomly divided into model group(MOD),low dose group(DBTL),medium dose group(DBTM),high dose group(DBTH)and irbesartan group(IRB).Each group was given intragastric administration for 20 weeks,during which CON group and MOD group were given the same amount of normal saline.Urine samples were collected after administration,and the ratio of urinary Microalbumin to urinary creatinine(UACR)was analyzed by automatic analyzer.The renal changes in each group were observed by hematoxylin-eosin(HE)staining,Masson pine(Masson)trichromatic staining and PASM staining.The expression of miR-155 and SOCS1mRNA in renal tissue of DKD rats was detected by Real-time PCR,and the expression of SOCS1 was detected by Western blotting.Results:By comparison with CON group,UACR value,MIR-155 mRNA expression and SOCS1 mRNA expression in MOD group increased significantly,while SOCS1 mRNA expression decreased significantly compared with MOD group,UACR decreased significantly in IRB group and DBT group,SOCS1 expression increased significantly in DBTM group,DBTH group and IRB group.The expression of MIR-155 decreased significantly in all treatment groups(P<0.05),and the expression of SOCS1 in DBTM group,DBTH group and IRB group increased significantly(P<0.05).Conclusion:Jiawei Danggui Buxuetang can reduce the expression of miR-155 in high glucose and increase the expression of SOCS1 in renal tissue,so as to significantly reduce renal damage and play a role in renal protection.展开更多
[Objectives]This study was conducted to explore the intervention mechanism of Danggui Buxue Decoction in perimenopausal syndrome based on network pharmacology and molecular docking.[Methods]The chemical components and...[Objectives]This study was conducted to explore the intervention mechanism of Danggui Buxue Decoction in perimenopausal syndrome based on network pharmacology and molecular docking.[Methods]The chemical components and targets of Danggui Buxue Decoction were acquired through the TCMSP database,and the main targets of perimenopausal syndrome were obtained through the GeneCards database.The component targets and disease targets were intersected,and combining with active components and Chinese herbs in the decoction,a traditional Chinese medicine-component-target network was constructed using Cytoscape 3.7.1 software.The STRING platform was employed for protein-protein interaction analysis.The DAVID analysis platform was used to conduct target GO and KEGG enrichment analysis,so as to predict the action mechanism Danggui Buxue Decoction.Finally,an active component-disease target-signal pathway network diagram was constructed.[Results]Twenty two components in Danggui Buxue Decoction related to perimenopausal syndrome and 120 corresponding targets were obtained,including active components such as 1,7-dihydroxy-3,9-dimquercetin and kaempferol,and key targets such as TNF,ESR1 and PPARG.The results of GO analysis and KEEG analysis indicated that Danggui Buxue Decoction might regulate the transcription of RNA polymerase II promoter,DNA templating,gene expression,signal transduction,hypoxia response and other biological processes by regulating multiple signal pathways such as chemical carcinogenesis-receptor activation,cancer pathways,lipid and atherosclerosis,tryptophan metabolism,malaria,steroid hormone biosynthesis and chemical carcinogenesis-DNA adduct.[Conclusions]Danggui Buxue Decoction intervenes in perimenopausal syndrome through multiple components,targets and pathways,providing a basis for elucidating the intervention mechanism of Danggui Buxue Decoction and expanding its clinical application.展开更多
Objective:To investigate the mechanism by which Astragalus mongholicus Bunge(AM),and Angelica sinensis Diels(AS)act in interstitial lung disease(ILD)based on computational prediction.Methods:We screened the ingredient...Objective:To investigate the mechanism by which Astragalus mongholicus Bunge(AM),and Angelica sinensis Diels(AS)act in interstitial lung disease(ILD)based on computational prediction.Methods:We screened the ingredients of AM and AS in PubMed,the Web of Science,China National Knowledge Infrastructure(CNKI)Databases,etc.Then obtained the potential effective components.By sharing the same molecular with ILD,we got the possible target genes for ILD treatment and constructed components–targets–disease network with Cytoscape software.The CTD(Comparative Toxicogenomics Database)database was used for GO and KEGG enrichment analysis of these target genes.Results:59 active ingredients that can be druggable were chosen from AM,67 active ingredients were chosen from AS.77 overlapping target genes for AM and ILD and 36 overlapping target genes for AS and ILD were acquired.The hub targets of AM were PTGS2,PTGS1,CDK2,MAOA,ESR1,TOP2A,GSK3B,ESR2,PPARG,NOS2,The hub targets of AS were PTGS2,GABRA1,PTGS1,CHRM1,SLC6A2,ADRA1B,ADRAIA,ADRB2,CHRM3,GABRA2,CHRM2.Quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,and 5-Hydroxycoumarin were the main active ingredients which have more effective targets.Prediction of the protein-protein interaction network showed PTGS2,GSK3B,PPARG,etc.,were the important predicted targets.The enriched KEGG pathways,including the Immune System,Metabolism of lipids and lipoproteins,Cytokine Signaling in the Immune system,Generic Transcription Pathway,The interleukin pathway,Metabolism of proteins,PI3K-Akt signaling pathway,Metabolic pathways,Innate Immune System,Neuroactive ligand-receptor interaction,Metabolism,GPCR downstream signaling,Amine ligand-binding receptors,Class A/1,Calcium signaling pathway.Molecular docking showed that quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,5-Hydroxycoumarin had good binding activities with PTGS2 and GSK3B,which mainly mediated PI3K/Akt and other important signaling pathways in the pathogenesis of ILD.Conclusion:The components in AS and AM share some common targets,such as PTGS2.AM and AS may ameliorate ILD through the PI3K-Akt signaling pathway which is mediated by GSK3B.PTGS2,PPARG may also be vital target genes in the treatment of ILD with AM and AS.展开更多
Background:Traditional Chinese medicine(TCM)has been shown to be effective in treating ischemic stroke(IS),and the combination of Angelicae Sinensis Radix(ASR)and Astragali Radix(AR)is a core TCM prescription that is ...Background:Traditional Chinese medicine(TCM)has been shown to be effective in treating ischemic stroke(IS),and the combination of Angelicae Sinensis Radix(ASR)and Astragali Radix(AR)is a core TCM prescription that is widely acknowledged for its efficacy in IS treatment.This study utilized network pharmacology methods to explore the molecular mechanisms underlying the therapeutic effects of Angelicae Sinensis Radix and Astragali Radix in IS treatment,with preliminary validation conducted through molecular docking.Methods:Information on the structure,targets,main biological functions,and pathways of the active components in Angelicae Sinensis Radix and Astragali Radix was collected using databases such as PubChem,PharmMapper,UniProt,and GeneCards.The results were visualized using software such as Cytoscape 3.6.1,Ledock,and pymol.Results:We retrieved 20 active components and 149 targets associated with the compatibility of Angelicae Sinensis Radix and Astragali Radix from various databases,and GeneCards database was used to search 3350 IS-related gene targets,including 78 key targets of Angelicae Sinensis Radix and Astragali Radix for the treatment of IS.Enrichment analysis of these 78 targets using gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)revealed the involvement of 48 GO terms in the treatment of IS,mainly in biological processes such as metabolism,biological regulation,and stress response.The composition of biological devices such as supercavitary membrane,cell fluid,and extracellular space was also involved.The biological functions mainly included protein binding,ion binding,hydrolytic enzyme activity,and others.The identified pathways were estrogen signaling pathway,mitogen-activated protein kinase(MAPK)signaling pathway,PI3K-AKT signaling pathway,RAP1 signaling pathway,P53 signaling pathway,PPAR signaling pathway,FOXO signaling pathway,RAS signaling pathway,prolactin signaling pathway,HIF-1 signaling pathway,and TNF signaling pathway.Molecular docking analysis showed that the 17 key active components of Angelicae Sinensis Radix and Astragali Radix had strong binding activity with 13 IS key targets.Conclusion:Through the application of network pharmacology methods,it was found that the use of Angelicae Sinensis Radix and Astragali Radix for treating ischemic stroke mainly targets the MAPK and PI3K-AKT signaling pathways,involving several crucial compounds and genes.Nevertheless,additional in vitro and in vivo studies are needed to verify these findings.展开更多
基金Natural Science Foundation of Shanxi Province for Youths,Grant/Award Number:20210302123310 and 20210302124668Science and technology innovation ability cultivation program project of Shanxi University of Chinese Medicine,Grant/Award Number:2022PY-TH-17The immune regulation Chinese medicine research and development innovation team project,Grant/Award Number:2022TD1017。
文摘Background:According to traditional Chinese medicine(TCM),drugs supplementing the vital energy,Qi,can eliminate tumors by restoring host immunity.The objective of this study is to investigate the underlying immune mechanisms of anti-tumor activity associated with Qi-supplementing herbs,specifically the paired use of Huangqi and Danggui.Methods:Analysis of compatibility regularity was conducted to screen the combination of Qi-supplementing TCMs.Using the MTT assay and a transplanted tumor mice model,the anti-tumor effects of combination TCMs were investigated in vitro and in vivo.High content analysis and flow cytometry were then used to evaluate cellular immunity,followed by network pharmacology and molecular docking to dissect the significant active compounds and potential mechanisms.Finally,the anti-tumor activity and the mechanism of the active ingredients were verified by molecular experiments.Results:There is an optimal combination of Huangqi and Danggui that,administered as an aqueous extract,can activate immunity to suppress tumor and is more effective than each drug on its own in vitro and in vivo.Based on network pharmacology analysis,PIK3R1 is the core target for the anti-tumor immunity activity of combined Huangqi and Danggui.Molecular docking analysis shows 6 components of the combined Danggui and Huangqi extract(quercetin,jaranol,isorhamnetin,kaempferol,calycosin,and suchilactone)that bind to PIK3R1.Jaranol is the most important component against breast cancer.The suchilactone/jaranol combination and,especially,the suchilactone/kaempferol combination are key for immunity enhancement and the anti-tumor effects of the extract.Conclusions:The combination of Huangqi and Danggui can activate immunity to suppress breast cancer and is more effective than the individual drugs alone.
基金supported by the National Natural Science Foundation of China(82074325).
文摘Objective:To observe the effects of Danggui Shaoyao powder(DSP)on hepatic lipid metabolism and further explore its mechanism of action by peroxisome proliferator-activated receptor(PPARγ)-liver X receptor(LXRα)-adenosine triphosphate(ATP)-binding cassette transporter A1(ABCA1)pathway regulation.Methods: Eight C57BL/6J male mice were selected as the control group,and 24 ApoE^(−/−)male mice were randomly divided into the atherosclerosis model(AS)group,atorvastatin calcium(AC)group,and DSP group(n=8 each group).To establish an AS model,ApoE^(−/−)mice were fed a high-fat diet for 16 weeks.Pathologic changes in the aortic vasculature and liver were identified using Oil Red O staining.Triglyceride(TG),cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)levels were determined in the livers using a single-reagent GPO-PAP method.Fluorescence quantitative polymerase chain reaction and western blot were used to observe and evaluate the mRNA and protein expression of the PPARγ-LXRα-ABCA1 intermediates in the liver.Results: After 16 weeks of a high-fat diet,ApoE^(−/−)mice showed more Oil Red O staining in the aorta and liver compared to the CONT group.Compared to the AS group,the DSP and AC treatment reduced aortic plaque and hepatic lipid deposition to varying degrees.Furthermore,DSP significantly reduced the hepatic lipid area in ApoE^(−/−)mice(P<.001)and decreased the levels of TG,TC,and LDL-C in liver(P<.001,P=.027,P<.001,respectively).DSP also significantly increased the levels of PPARγ,LXRα,ABCA1,and ABCG1 mRNA expression,as well as the PPARγ,LXRα,ABCA1,and ABCG1 protein expression in liver.Conclusion: DSP improved hepatic lipid metabolism via PPARγ-LXRα-ABCA1 pathway modulation for AS treatment.
文摘Chronic myeloid leukemia(CML)is a hematopoietic myeloproliferative disorder.The Chinese prescription Danggui Longhui Wan(DGLHW)has been utilized in CML treatment,but its underlying mechanisms remain unclear.In this study,we gathered 794 constituents,1249 drug targets,1654 disease genes and 129 intersection genes.GO and KEGG were used to analyze the function of these genes.Compatibility of prescription study showed that monarch drug,minister drug,assistant and guide drug played a synergistic role in the treatment of CML.In addition,we obtained 20 hub genes and 12 key components.Molecular docking indicated that the main compounds and core proteins had good binding ability.The results of this study also showed that DGLHW might play a role in the treatment of CML by affecting MAPK,PI3K/AKT,FoxO and p53 signaling pathways.
基金sponsored by the National Natural Science Foundation (81822050,81920108032)Young Qihuang Scholar of State Administration of Traditional Chinese Medicine of Qianqian Liang,Innovation Team Project of the Scientific Research Project of Traditional Chinese Medicine of Shanghai Health Committee (2022CX001)+2 种基金Shanghai Hospital Chinese Medicine Preparation Industry Transformation Synergy Innovation Center of Qianqian Liang,Program for Innovative Research Team of Ministry of Science and Technology of China (2015RA4002),“Innovation Team”Development Projects (IRT1270)Shanghai TCM Medical Center of Chronic Disease (2022ZZ01009)Jing’an District Health Research Project of Shanghai (2022MS03).
文摘Objective:Rheumatoid arthritis(RA)is a common autoimmune disease characterized by multiple joint lesions and systemic complications.Danggui Niantong decoction(DGNTT)has been clinically used for RA treatment;however,its beneficial effect on cardiopulmonary complications has not been reported.Methods:Female tumor necrosis factor-transgenic(TNF-Tg)mice were used to evaluate the therapeutic effects of DGNTT on arthritis and cardiopulmonary complications.Methotrexate(MTX)served as a positive control.Histopathological assessment of the joint sections was performed using hematoxylin and eosin(HE),Alcian Blue/Orange G,and tartrate-resistant acid phosphatase staining.Bone mass was assessed by micro-computed tomography,inflammatory infiltrates in the heart and lungs were evaluated by HE staining,cardiopulmonary fibrotic injury was identified by Masson’s trichrome staining,and hypertrophy of mouse cardiomyocytes was measured by wheat germ agglutinin(WGA)staining.Results:DGNTT mitigated the inflammation of the ankle joint synovium,decreased the number of osteoclasts,and increased the area of cartilage and bone mass in TNF-Tg mice.In addition,DGNTT decreased the infiltration of inflammatory cells into the lung and heart tissues,accompanied by a reduction in cardiopulmonary fibrosis and myocardial cell hypertrophy in TNF-Tg mice.As a positive control drug,MTX attenuated the pathological changes in joints,but had no beneficial effect on cardiopulmonary inflammation and fibrosis in TNF-Tg mice.Conclusions:DGNTT improved joint lesions and alleviated cardiopulmonary complications in TNF-Tg mice.
基金supported by the Government Subsidizes the Training Program for Clinical Medical Talents(13000022P00DE341002470)Scientific Research Project of Hebei Administration of Traditional Chinese Medicine(2021167)Graduate Innovation Ability Training Program of Hebei University of Traditional Chinese Medicine(XCXZZBS2022018)。
文摘Objective:To observe the effect of Jiawei Danggui Buxuetang on the expression of microRNA-155(miR-155)and cytokine signal transduction inhibitor 1(SOCS1)in renal tissue of rats with diabetic nephropathy(DKD),and to explore the mechanism of Jiawei Danggui Buxuetang in the treatment of DKD.Methods:Firty 6-week-old SPF male SD rats were randomly divided into normal group(CON)and model group.The model group was fed with high-sugar and high-fat diet for 6 weeks,and the DKD rat model was established by intraperitoneal injection of streptozotocin(STZ)(35 mg/kg).Then the rats were randomly divided into model group(MOD),low dose group(DBTL),medium dose group(DBTM),high dose group(DBTH)and irbesartan group(IRB).Each group was given intragastric administration for 20 weeks,during which CON group and MOD group were given the same amount of normal saline.Urine samples were collected after administration,and the ratio of urinary Microalbumin to urinary creatinine(UACR)was analyzed by automatic analyzer.The renal changes in each group were observed by hematoxylin-eosin(HE)staining,Masson pine(Masson)trichromatic staining and PASM staining.The expression of miR-155 and SOCS1mRNA in renal tissue of DKD rats was detected by Real-time PCR,and the expression of SOCS1 was detected by Western blotting.Results:By comparison with CON group,UACR value,MIR-155 mRNA expression and SOCS1 mRNA expression in MOD group increased significantly,while SOCS1 mRNA expression decreased significantly compared with MOD group,UACR decreased significantly in IRB group and DBT group,SOCS1 expression increased significantly in DBTM group,DBTH group and IRB group.The expression of MIR-155 decreased significantly in all treatment groups(P<0.05),and the expression of SOCS1 in DBTM group,DBTH group and IRB group increased significantly(P<0.05).Conclusion:Jiawei Danggui Buxuetang can reduce the expression of miR-155 in high glucose and increase the expression of SOCS1 in renal tissue,so as to significantly reduce renal damage and play a role in renal protection.
基金Supported by Project of Science and Technology Department of Guizhou Province(ZK[2021]-546)Project of Science and Technology Department of Guizhou Province([2019]1401)+1 种基金Guizhou Administration of Traditional Chinese Medicine(QZYY-2021-03)Guizhou Provincial Health Commission(gzwkj2021-464).
文摘[Objectives]This study was conducted to explore the intervention mechanism of Danggui Buxue Decoction in perimenopausal syndrome based on network pharmacology and molecular docking.[Methods]The chemical components and targets of Danggui Buxue Decoction were acquired through the TCMSP database,and the main targets of perimenopausal syndrome were obtained through the GeneCards database.The component targets and disease targets were intersected,and combining with active components and Chinese herbs in the decoction,a traditional Chinese medicine-component-target network was constructed using Cytoscape 3.7.1 software.The STRING platform was employed for protein-protein interaction analysis.The DAVID analysis platform was used to conduct target GO and KEGG enrichment analysis,so as to predict the action mechanism Danggui Buxue Decoction.Finally,an active component-disease target-signal pathway network diagram was constructed.[Results]Twenty two components in Danggui Buxue Decoction related to perimenopausal syndrome and 120 corresponding targets were obtained,including active components such as 1,7-dihydroxy-3,9-dimquercetin and kaempferol,and key targets such as TNF,ESR1 and PPARG.The results of GO analysis and KEEG analysis indicated that Danggui Buxue Decoction might regulate the transcription of RNA polymerase II promoter,DNA templating,gene expression,signal transduction,hypoxia response and other biological processes by regulating multiple signal pathways such as chemical carcinogenesis-receptor activation,cancer pathways,lipid and atherosclerosis,tryptophan metabolism,malaria,steroid hormone biosynthesis and chemical carcinogenesis-DNA adduct.[Conclusions]Danggui Buxue Decoction intervenes in perimenopausal syndrome through multiple components,targets and pathways,providing a basis for elucidating the intervention mechanism of Danggui Buxue Decoction and expanding its clinical application.
基金Funded by National Natural Science Foundation of China(81903934)Tianjin Health Science and Technology Project(ZC20205).
文摘Objective:To investigate the mechanism by which Astragalus mongholicus Bunge(AM),and Angelica sinensis Diels(AS)act in interstitial lung disease(ILD)based on computational prediction.Methods:We screened the ingredients of AM and AS in PubMed,the Web of Science,China National Knowledge Infrastructure(CNKI)Databases,etc.Then obtained the potential effective components.By sharing the same molecular with ILD,we got the possible target genes for ILD treatment and constructed components–targets–disease network with Cytoscape software.The CTD(Comparative Toxicogenomics Database)database was used for GO and KEGG enrichment analysis of these target genes.Results:59 active ingredients that can be druggable were chosen from AM,67 active ingredients were chosen from AS.77 overlapping target genes for AM and ILD and 36 overlapping target genes for AS and ILD were acquired.The hub targets of AM were PTGS2,PTGS1,CDK2,MAOA,ESR1,TOP2A,GSK3B,ESR2,PPARG,NOS2,The hub targets of AS were PTGS2,GABRA1,PTGS1,CHRM1,SLC6A2,ADRA1B,ADRAIA,ADRB2,CHRM3,GABRA2,CHRM2.Quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,and 5-Hydroxycoumarin were the main active ingredients which have more effective targets.Prediction of the protein-protein interaction network showed PTGS2,GSK3B,PPARG,etc.,were the important predicted targets.The enriched KEGG pathways,including the Immune System,Metabolism of lipids and lipoproteins,Cytokine Signaling in the Immune system,Generic Transcription Pathway,The interleukin pathway,Metabolism of proteins,PI3K-Akt signaling pathway,Metabolic pathways,Innate Immune System,Neuroactive ligand-receptor interaction,Metabolism,GPCR downstream signaling,Amine ligand-binding receptors,Class A/1,Calcium signaling pathway.Molecular docking showed that quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,5-Hydroxycoumarin had good binding activities with PTGS2 and GSK3B,which mainly mediated PI3K/Akt and other important signaling pathways in the pathogenesis of ILD.Conclusion:The components in AS and AM share some common targets,such as PTGS2.AM and AS may ameliorate ILD through the PI3K-Akt signaling pathway which is mediated by GSK3B.PTGS2,PPARG may also be vital target genes in the treatment of ILD with AM and AS.
基金funded by the Natural Science Foundation of China(No.81874416)Science,Technology Innovation Team Project of Hunan(No.2020RC4050).
文摘Background:Traditional Chinese medicine(TCM)has been shown to be effective in treating ischemic stroke(IS),and the combination of Angelicae Sinensis Radix(ASR)and Astragali Radix(AR)is a core TCM prescription that is widely acknowledged for its efficacy in IS treatment.This study utilized network pharmacology methods to explore the molecular mechanisms underlying the therapeutic effects of Angelicae Sinensis Radix and Astragali Radix in IS treatment,with preliminary validation conducted through molecular docking.Methods:Information on the structure,targets,main biological functions,and pathways of the active components in Angelicae Sinensis Radix and Astragali Radix was collected using databases such as PubChem,PharmMapper,UniProt,and GeneCards.The results were visualized using software such as Cytoscape 3.6.1,Ledock,and pymol.Results:We retrieved 20 active components and 149 targets associated with the compatibility of Angelicae Sinensis Radix and Astragali Radix from various databases,and GeneCards database was used to search 3350 IS-related gene targets,including 78 key targets of Angelicae Sinensis Radix and Astragali Radix for the treatment of IS.Enrichment analysis of these 78 targets using gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)revealed the involvement of 48 GO terms in the treatment of IS,mainly in biological processes such as metabolism,biological regulation,and stress response.The composition of biological devices such as supercavitary membrane,cell fluid,and extracellular space was also involved.The biological functions mainly included protein binding,ion binding,hydrolytic enzyme activity,and others.The identified pathways were estrogen signaling pathway,mitogen-activated protein kinase(MAPK)signaling pathway,PI3K-AKT signaling pathway,RAP1 signaling pathway,P53 signaling pathway,PPAR signaling pathway,FOXO signaling pathway,RAS signaling pathway,prolactin signaling pathway,HIF-1 signaling pathway,and TNF signaling pathway.Molecular docking analysis showed that the 17 key active components of Angelicae Sinensis Radix and Astragali Radix had strong binding activity with 13 IS key targets.Conclusion:Through the application of network pharmacology methods,it was found that the use of Angelicae Sinensis Radix and Astragali Radix for treating ischemic stroke mainly targets the MAPK and PI3K-AKT signaling pathways,involving several crucial compounds and genes.Nevertheless,additional in vitro and in vivo studies are needed to verify these findings.