Objective To investigate the effects of matrine on antigen presentation of dendritic cells(DCs),and to explore the pharmacological mechanism of matrine on anti-tumor effect.Methods Different concentrations(0,1,2,4,8 a...Objective To investigate the effects of matrine on antigen presentation of dendritic cells(DCs),and to explore the pharmacological mechanism of matrine on anti-tumor effect.Methods Different concentrations(0,1,2,4,8 and 16µg/mL)of matrine were co-cultured with DCs,the harvested DCs were co-cultured with antigens of Lewis lung cancer(LLC)cells,and then DCs and T cells were co-cultured to produce DCs-activated killer(DAK)cells,which have significant tumor-killing activity.The expression of cytokines,mRNA and protein of toll-like receptors(TLRs)in DCs were detected by enzyme linked immunosobent assay,polymerase chain reaction and Western blot,respectively.And the killing effect of DAK were measured by MTT assay.Results Matrine significantly increased the mRNA expression of TLR7,TLR8,myeloid differentiation factor 88(MyD88),tumor necrosis factor receptor-associated factor 6(TRAF-6)and IκB kinase(IKK),as well as the protein expression of TLR7 and TLR8,and up-regulated the levels of interleukin-12(IL-12),IL-6 and tumor necrosis factor-α(TNF-α),meanwhile,it also increased the expressions of MHC-II,CD54,CD80 and CD86 in DCs.DCs-activated effector T cells had significant tumor-killing activity.When the concentration of matrine was more than 4µg/mL,all indices had significant difference(P<0.01 or P<0.05).Conclusion Matrine plays an anti-tumor role by regulating TLRs signal transduction pathway,promoting the secretion of inflammatory cytokines and enhancing immune function.展开更多
Objective:To explore whether Panax notoginseng saponins(PNS)exhibits heart protective effect in myocardial infarction(MI)rats and to identify the potential signaling pathways involved.Methods:MI rats induced by ligati...Objective:To explore whether Panax notoginseng saponins(PNS)exhibits heart protective effect in myocardial infarction(MI)rats and to identify the potential signaling pathways involved.Methods:MI rats induced by ligating the left anterior descending(LAD)coronary artery were assigned to sham coronary artery ligation or coronary artery ligation.Totally 36 Sprague-Dawley rats were randomly divided into sham group(distilled water,n=9),MI group(distilled water,n=9),PNS group(PNS,40 mg/kg daily,n=9)and fosinopril group(FIP,1.2 mg/kg daily,n=9)according to a random number table.The left ventricular morphology and function were conducted by echocardiography.Histological alterations were evaluated by the stainings of HE and Masson.The serum levels of C reactive protein(CRP),tumor necrosis factorα(TNF-α),growth differentiation factor-15(GDF-15)and the ratio of metalloproteinase-9(MMP-9)and tissue inhibitor of MMP-9(TIMP-1)were determined by ELISA.The levels of activating transcription factor 3(ATF3),mitogen-activated protein kinase kinase 3(MAP2 K3),p38 mitogen-activated protein kinase(p38 MAPK),phosphorylation of p38 MAPK(p-p38 MAPK),transforming growth factor-β(TGF-β1),collagenⅠ,nuclear factor kappa B p65(NFκB p65),phosphorylation of NFκB p65(p-NFκB p65),and phosphorylation of inhibitory kappa Bα(p-IκBα)in hearts were measured by Western blot and immunohistochemical staining,respectively.Results:PNS improved cardiac function and fibrosis in MI rats(P<0.05).The serum levels of CRP,TNF-α,GDF-15 and the ratio of MMP9/TIMP1 were reversed by PNS in MI rats.The expressions of TGF-β1,collagenⅠ,MAP2 K3,p38 MAPK,p-p38 MAPK,NFκB p65,p-NFκB p65,and p-IκBαwere down-regulated,while ATF3 increased with the treatment of PNS(P<0.05).Conclusions:PNS may improve cardiac function and fibrosis in MI rats via regulating ATF3/MAP2 K3/p38 MAPK and NFκB signaling pathways.These results suggest the potential of PNS in preventing the development of ventricular remodeling in MI rats.展开更多
基金Supported by the National Natural Science Foundation of China(Nos.81773960 and 81973535)。
文摘Objective To investigate the effects of matrine on antigen presentation of dendritic cells(DCs),and to explore the pharmacological mechanism of matrine on anti-tumor effect.Methods Different concentrations(0,1,2,4,8 and 16µg/mL)of matrine were co-cultured with DCs,the harvested DCs were co-cultured with antigens of Lewis lung cancer(LLC)cells,and then DCs and T cells were co-cultured to produce DCs-activated killer(DAK)cells,which have significant tumor-killing activity.The expression of cytokines,mRNA and protein of toll-like receptors(TLRs)in DCs were detected by enzyme linked immunosobent assay,polymerase chain reaction and Western blot,respectively.And the killing effect of DAK were measured by MTT assay.Results Matrine significantly increased the mRNA expression of TLR7,TLR8,myeloid differentiation factor 88(MyD88),tumor necrosis factor receptor-associated factor 6(TRAF-6)and IκB kinase(IKK),as well as the protein expression of TLR7 and TLR8,and up-regulated the levels of interleukin-12(IL-12),IL-6 and tumor necrosis factor-α(TNF-α),meanwhile,it also increased the expressions of MHC-II,CD54,CD80 and CD86 in DCs.DCs-activated effector T cells had significant tumor-killing activity.When the concentration of matrine was more than 4µg/mL,all indices had significant difference(P<0.01 or P<0.05).Conclusion Matrine plays an anti-tumor role by regulating TLRs signal transduction pathway,promoting the secretion of inflammatory cytokines and enhancing immune function.
基金Supported by the National Significant New Drugs Development(No.2013ZX09301307)National Natural Science Foundation of China(No.81774168)。
文摘Objective:To explore whether Panax notoginseng saponins(PNS)exhibits heart protective effect in myocardial infarction(MI)rats and to identify the potential signaling pathways involved.Methods:MI rats induced by ligating the left anterior descending(LAD)coronary artery were assigned to sham coronary artery ligation or coronary artery ligation.Totally 36 Sprague-Dawley rats were randomly divided into sham group(distilled water,n=9),MI group(distilled water,n=9),PNS group(PNS,40 mg/kg daily,n=9)and fosinopril group(FIP,1.2 mg/kg daily,n=9)according to a random number table.The left ventricular morphology and function were conducted by echocardiography.Histological alterations were evaluated by the stainings of HE and Masson.The serum levels of C reactive protein(CRP),tumor necrosis factorα(TNF-α),growth differentiation factor-15(GDF-15)and the ratio of metalloproteinase-9(MMP-9)and tissue inhibitor of MMP-9(TIMP-1)were determined by ELISA.The levels of activating transcription factor 3(ATF3),mitogen-activated protein kinase kinase 3(MAP2 K3),p38 mitogen-activated protein kinase(p38 MAPK),phosphorylation of p38 MAPK(p-p38 MAPK),transforming growth factor-β(TGF-β1),collagenⅠ,nuclear factor kappa B p65(NFκB p65),phosphorylation of NFκB p65(p-NFκB p65),and phosphorylation of inhibitory kappa Bα(p-IκBα)in hearts were measured by Western blot and immunohistochemical staining,respectively.Results:PNS improved cardiac function and fibrosis in MI rats(P<0.05).The serum levels of CRP,TNF-α,GDF-15 and the ratio of MMP9/TIMP1 were reversed by PNS in MI rats.The expressions of TGF-β1,collagenⅠ,MAP2 K3,p38 MAPK,p-p38 MAPK,NFκB p65,p-NFκB p65,and p-IκBαwere down-regulated,while ATF3 increased with the treatment of PNS(P<0.05).Conclusions:PNS may improve cardiac function and fibrosis in MI rats via regulating ATF3/MAP2 K3/p38 MAPK and NFκB signaling pathways.These results suggest the potential of PNS in preventing the development of ventricular remodeling in MI rats.
