Effects of Platycodonis Radix Total Saponins on the Proliferation, Migration and Notch1/Jagged1 Pathway of Mouse Airway Smooth Muscle Cells

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/Notch1 (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 supernatant 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.