Hypertension represents a significant chronic non-infectious disease in China,where Qingda Granule(QDG)has traditionally been employed for its management.However,the mechanisms underlying QDG's kidney protective e...Hypertension represents a significant chronic non-infectious disease in China,where Qingda Granule(QDG)has traditionally been employed for its management.However,the mechanisms underlying QDG's kidney protective effects remain incompletely understood.This study investigates QDG's role in ameliorating hypertensive kidney injury(KI)and elucidates the associated mechanisms.Network analysis identified potential therapeutic targets related to mitochondrial function and the extracellular signal-regulated kinase(ERK)cascade.Ribonucleic acid(RNA)sequencing revealed differentially expressed genes(DEGs)in hypertensive mouse kidneys,which were enriched in mitochondrial-related functions and normalized by QDG treatment.QDG attenuated angiotensin II(Ang II)-induced blood pressure elevation and enhanced renal artery flow.Both cellular and animal experiments demonstrated that QDG inhibits the ERK/ribosomal S6 kinase 1(RSK1)signaling axis,thereby preventing Ang II-induced mitochondrial damage and renal cell apoptosis.ERK pathway inhibitors confirmed QDG's mechanism of action through the ERK/RSK1 pathway.These findings indicate that QDG ameliorates hypertensive KI by preserving mitochondrial function through modulation of the ERK/RSK1 network,presenting a novel therapeutic approach for managing hypertensive KI in clinical practice.展开更多
Objective To investigate the effect of Qingda Granules(QDG)on renal artery fibrosis induced by hypertension.Methods Six WKY rats were selected to serve as the control group.Totally 30 spontaneously hypertensive rats(S...Objective To investigate the effect of Qingda Granules(QDG)on renal artery fibrosis induced by hypertension.Methods Six WKY rats were selected to serve as the control group.Totally 30 spontaneously hypertensive rats(SHRs)were randomly divided into the model group,low-dose QDG group,medium-dose QDG group,high-dose QDG group,and the positive drug group,with six rats in each group.The QDG low,medium,and high dose groups were administered with QDG intragastrically at doses of 450,900,and 1800 mg·kg*1.d-1,respectively,while the positive drug group was given valsartan intragastrically at a dose of 7.2 mg:kg-1.d-1.Both the control and model groups were intragastrically administered with an equivalent volume of double-distilled water,once daily for 10 consecutive weeks.HE staining was used to detect the pathological changes of renal artery tissue.RNA sequencing was used to analyze differentially expressed transcripts,and Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)were used to analyze the potential pathways.Angiotensin II(Ang II)stimulation was used to establish a model of rat renal artery vascular smooth muscle cells to verify the effects of different doses of QDG on fibrosis and activation of potential enrichment pathways.Results QDG significantly reduced the thickness of renal artery media in SHR rats(P<0.05).RNA sequencing analysis indicated that 1423 dfferential transcripts changed after QDG intervention.GO analysis showed that cellular processes and biological processes were significantly enriched.KEGG analysis found that mitogen-activated protein kinase(MAPK),transforming growth factorβ(TGF-β)and other pathways were significantly enriched.QDG significantly inhibited the protein expressions of Collagen I,Collagen II,matrix metalloproteinase 9(MMP-9),p-Smad2,p-Smad3,and TGF-β1 in rat renal artery vascular smooth muscle cells stimulated byAngg II,and increased the protein expressions of tissue inhibitor of metalloproteinase(TIMP)1 and TIMP2(P<0.05).Conclusion QDG inhibits the activation of TGFβ-1/Smad2/3 pathway to reduce renal artery fibrosis induced by hypertension.展开更多
Objective:To assess the efficacy of Qingda Granule(QDG)in ameliorating hypertensioninduced cardiac damage and investigate the underlying mechanisms involved.Methods:Twenty spontaneously hypertensive rats(SHRs)were use...Objective:To assess the efficacy of Qingda Granule(QDG)in ameliorating hypertensioninduced cardiac damage and investigate the underlying mechanisms involved.Methods:Twenty spontaneously hypertensive rats(SHRs)were used to develope a hypertension-induced cardiac damage model.Another 10Wistar Kyoto(WKY)rats were used as normotension group.Rats were administrated intragastrically QDG[0.9 g/(kg·d)]or an equivalent volume of pure water for 8 weeks.Blood pressure,histopathological changes,cardiac function,levels of oxidative stress and inflammatory response markers were measured.Furthermore,to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertensioninduced cardiac injury,a network pharmacology study was conducted.Predicted results were validated by Western blot,radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction,respectively.Results:The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs(P<0.01).Histological examinations,including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage.Furthermore,echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction.Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum(P<0.01).Conclusion:Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertensioninduced cardiac damage by regulating the angiotensin converting enzyme(ACE)/angiotensinⅡ(AngⅡ)/AngⅡreceptor type 1 axis and ACE/AngⅡ/AngⅡreceptor type 2 axis.展开更多
基金supported by the National Natural Science Foundation of China(Nos.U22A20372,82204662,82374359,82204662)the Fujian Province Natural Science Foundation(Nos.2022J01369,2021J1942)+1 种基金the Developmental Fund of Chen Keji Integrative Medicine(No.CKJ2022010)the Fujian Natural Science Foundation for Distinguished Young Scholars(No.2024J010032)。
文摘Hypertension represents a significant chronic non-infectious disease in China,where Qingda Granule(QDG)has traditionally been employed for its management.However,the mechanisms underlying QDG's kidney protective effects remain incompletely understood.This study investigates QDG's role in ameliorating hypertensive kidney injury(KI)and elucidates the associated mechanisms.Network analysis identified potential therapeutic targets related to mitochondrial function and the extracellular signal-regulated kinase(ERK)cascade.Ribonucleic acid(RNA)sequencing revealed differentially expressed genes(DEGs)in hypertensive mouse kidneys,which were enriched in mitochondrial-related functions and normalized by QDG treatment.QDG attenuated angiotensin II(Ang II)-induced blood pressure elevation and enhanced renal artery flow.Both cellular and animal experiments demonstrated that QDG inhibits the ERK/ribosomal S6 kinase 1(RSK1)signaling axis,thereby preventing Ang II-induced mitochondrial damage and renal cell apoptosis.ERK pathway inhibitors confirmed QDG's mechanism of action through the ERK/RSK1 pathway.These findings indicate that QDG ameliorates hypertensive KI by preserving mitochondrial function through modulation of the ERK/RSK1 network,presenting a novel therapeutic approach for managing hypertensive KI in clinical practice.
文摘Objective To investigate the effect of Qingda Granules(QDG)on renal artery fibrosis induced by hypertension.Methods Six WKY rats were selected to serve as the control group.Totally 30 spontaneously hypertensive rats(SHRs)were randomly divided into the model group,low-dose QDG group,medium-dose QDG group,high-dose QDG group,and the positive drug group,with six rats in each group.The QDG low,medium,and high dose groups were administered with QDG intragastrically at doses of 450,900,and 1800 mg·kg*1.d-1,respectively,while the positive drug group was given valsartan intragastrically at a dose of 7.2 mg:kg-1.d-1.Both the control and model groups were intragastrically administered with an equivalent volume of double-distilled water,once daily for 10 consecutive weeks.HE staining was used to detect the pathological changes of renal artery tissue.RNA sequencing was used to analyze differentially expressed transcripts,and Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)were used to analyze the potential pathways.Angiotensin II(Ang II)stimulation was used to establish a model of rat renal artery vascular smooth muscle cells to verify the effects of different doses of QDG on fibrosis and activation of potential enrichment pathways.Results QDG significantly reduced the thickness of renal artery media in SHR rats(P<0.05).RNA sequencing analysis indicated that 1423 dfferential transcripts changed after QDG intervention.GO analysis showed that cellular processes and biological processes were significantly enriched.KEGG analysis found that mitogen-activated protein kinase(MAPK),transforming growth factorβ(TGF-β)and other pathways were significantly enriched.QDG significantly inhibited the protein expressions of Collagen I,Collagen II,matrix metalloproteinase 9(MMP-9),p-Smad2,p-Smad3,and TGF-β1 in rat renal artery vascular smooth muscle cells stimulated byAngg II,and increased the protein expressions of tissue inhibitor of metalloproteinase(TIMP)1 and TIMP2(P<0.05).Conclusion QDG inhibits the activation of TGFβ-1/Smad2/3 pathway to reduce renal artery fibrosis induced by hypertension.
基金Supported by Natural Science Foundation of Xinjiang Uygur Autonomous Region(No.2022D01C556)National Natural Science Foundation of China(No.82104678)Science and Technology Innovation Project of China Academy of Chinese Medical Sciences(No.CI2021A05013)。
文摘Objective:To assess the efficacy of Qingda Granule(QDG)in ameliorating hypertensioninduced cardiac damage and investigate the underlying mechanisms involved.Methods:Twenty spontaneously hypertensive rats(SHRs)were used to develope a hypertension-induced cardiac damage model.Another 10Wistar Kyoto(WKY)rats were used as normotension group.Rats were administrated intragastrically QDG[0.9 g/(kg·d)]or an equivalent volume of pure water for 8 weeks.Blood pressure,histopathological changes,cardiac function,levels of oxidative stress and inflammatory response markers were measured.Furthermore,to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertensioninduced cardiac injury,a network pharmacology study was conducted.Predicted results were validated by Western blot,radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction,respectively.Results:The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs(P<0.01).Histological examinations,including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage.Furthermore,echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction.Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum(P<0.01).Conclusion:Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertensioninduced cardiac damage by regulating the angiotensin converting enzyme(ACE)/angiotensinⅡ(AngⅡ)/AngⅡreceptor type 1 axis and ACE/AngⅡ/AngⅡreceptor type 2 axis.
