Panax notoginseng saponin R1 improves glucocorticoid-inhibited airway epithelium repair via glucocorticoid receptor β.

BACKGROUND

Panax notoginseng saponin R1(PNS-R1), derived from Panax notoginseng roots, promotes wound repair, whereas glucocorticoids can inhibit the repair of airway epithelial damage in asthma.

OBJECTIVE

This study investigated whether PNS-R1 counteracts the inhibitory effects of glucocorticoids on the repair of airway epithelial damage in asthma.

METHODS

In vivo, female C57BL/6 mice were sensitized, challenged with house dust mites (HDM), and treated with dexamethasone, PNS-R1, and/or adenovirus GRβ-shRNA. Airway epithelium damage was examined using pathological sections of the trachea and bronchi, markers of airway inflammation, epithelial cells in bronchoalveolar lavage fluid, and expression of the E-cadherin protein. In vitro, we treated 16HBE cells with dexamethasone, PNS-R1, and/or GRβ-siRNA and detected cell proliferation and migration. The expression of GRβ and key components of MKP-1 and Erk1/2 were detected by western blotting.

RESULTS

In vivo, PNS-R1 reduced airway inflammation, hyperresponsiveness, and mucus hypersecretion; the combination of PNS-R1 and dexamethasone promoted airway epithelial integrity and reduced cell detachment. In vitro, PNS-R1 alleviated the inhibition of bronchial epithelial cell growth, migration, and proliferation by dexamethasone; PNS-R1 promoted GRβ expression, inhibited MKP-1 protein expression, and activated MAPK signaling, thereby promoting airway epithelial cell proliferation and repair.

CONCLUSIONS

Panax notoginseng saponin R1 alleviated the inhibitory effect of dexamethasone on the repair of airway epithelial damage in asthmatic mice, likely by promoting the proliferation of airway epithelial cells by stimulating GRβ expression and activating the MAPK pathway.