OBJECTIVE To investigate the effects of Platycodonis Radix total saponins on the proliferation and migration of airway smooth muscles(ASMCs)and the expression levels of Notch1/Jagged1 signaling pathway-related proteins in asthmatic mice.METHODS Primary mouse ASMCs were isolated and cultured,and administered in randomized groups according to the control group,platelet-derived growth factor(PDGF)group,10 μg·mL-1 Platycodonis Radix total saponins group,20 μg·mL-1 Platycodonis Radix total saponins group,40 μg·mL-1 Platycodonis Radix total saponins group and IL-17+40 μg·mL-1 Platycodonis Radix total saponins group.Notch1 overexpression lentivirus infected ASMCs,according to the control group,PDGF group,PDGF+40 μg·mL-1 Platycodonis Radix total saponins group,PDGF+40 μg·mL-1 Platycodonis Radix total saponins+pEGF-C1(Notch1 overexpression negative control plasmid)group and PDGF+40 μg·mL-1 Platycodonis Radix total saponins+pEGF-C1/Notch 1(Notch1 overexpression plasmid)group administration.The proliferation and migration ability of ASMCs were detected by CCK8 and scratch assay,the expression level of PCAN was detected by immunofluorescence,the level of inflammation-related factors in ASMCs supematant was detected by ELISA,and the expression level of Notch1/Jagged1 pathway-related proteins in ASMCs was detected by Western blotting.RESULTS Different doses of Platycodonis Radix total saponins can inhibit PDGF-induced cell proliferation and migration to varying degrees,inhibit the enhancement of proliferating cell nuclear antigen(PCNA)fluorescence expression in ASMCs,significantly inhibit the levels of IL-6 and IL-8 in the supernatant and the expressions of Notch1,Jagged1,and Hes1 proteins Level up(P＜0.05 or P＜0.01).Compared with the 40 μmol·L-1 Platycodonis Radix total saponins group,the cell viability,mobility and the levels of IL-6 and IL-8 in the supernatant of the IL-17+40 μmol·L-1 Platycodonis Radix total saponins group were significantly increased(P＜0.05 or P＜0.01),PCNA fluorescence expression intensity was significantly enhanced(P＜0.01),Notch1,Jagged1,Hes1 protein expression levels were significantly up-regulated(P＜0.05 or P＜0.01).Compared with the 40 μg·mL-1 Platycodonis Radix total saponins+pEGF-C1 group,the cell viability,migration rate and IL-6 and IL-8 levels in the supernatant of ASMCs in the 40 μg·mL-1 Platycodonis Radix total saponins+pEGF-C1/Notch1 group were significantly increased(P＜0.05 or P＜0.01),and the protein expression levels of Notch1,Jagged1,and Hes1 were significantly increased(P＜0.01).CONCLUSION The total saponin of Platycodon grandis inhibited the proliferation and migration of ASMCs,and its mechanism of action may be related to the down-regulation of Notch1/Jagged1 signaling pathway-related protein expression levels.
asthmaPlatycodonis Radix total saponinsairway smooth muscle cellsproliferationmigrationNotch1/Jagged1 signaling pathway
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