[Effects of glycyrrhizic acid on ERK1/2 and p38 MAPK signaling pathway in a murine model of asthma].

Objective: To explore the effects of glycyrrhizic acid (GA) on Extracellular regulated protein kinases (ERK1/2) and p38 mitogen-activated protein kinases (p38 MAPK) signaling pathways in a murine model of asthma. Methods: Sixty female BALB/c mice were randomly divided into 6 groups ( n =10 each): a control group, an asthmatic group, two treatment groups with low and high doses of GA, U0126 group and SB203580 group. Within 24 hours after the last OVA challenge, histological studies of lung were conducted with the hematoxylin and eosin staining (HE) and alcian blue-periodic acid-Schiff (AB-PAS), the relative protein expression of ERK1/2 and p38 MAPK were detected by immunohistochemistry and Western blotting in vivo . CD4(+) T cells were purified from spleens of OVA-sensitized and challenged mice by using the Mouse CD4 Cell Positive Isolation Kit and incubated with anti-CD3 mAb (1 μg/ml) in the presence of various concentrations of GA (10 and 100 μg/ml), U0126 (10 μmol/L) or SB203580(10 μmol/L). After 72 h of incubation, the relative protein expression of ERK1/2 and p38 MAPK of CD4(+) T cells were detected by Western blotting in vitro . Results: The asthmatic mice induced infiltration of inflammatory cells around airways and blood vessels, airway goblet cell hyperplasia and mucus production. Administration of GA at a dose of 100 mg/kg, U0126 or SB203580 significantly reduced the infiltration of inflammatory cells in the peribronchial areas and goblet cell hyperplasia compared with the asthmatic mice. The protein expressions of p-ERK1/2 were lower in GA at a dose of 100 mg/kg (0.090±0.022) and U0126 group (0.072±0.017) than those in asthmatic group (0.143±0.022) (all P <0.05). The protein expressions of p-p38 MAPK were lower in GA at a dose of 100 mg/kg (0.072±0.019) and SB203580 group (0.061±0.015) than those in asthmatic group (0.121±0.022) (all P <0.05) by immunohistochemistry. Compared with asthmatic group (0.783±0.133, 0.649±0.095), the protein expressions of p-ERK1/2 and p-p38 MAPK in GA at a high dose group (0.385±0.186, 0.275±0.089) and in U0126 group (0.117±0.051) or in SB203580 group (0.108±0.043) were decreased by Western blotting (all P <0.05). The expressions of p-ERK1/2 in CD4(+) T cells after 72 h incubation were lower in 100 μg/ml concentrations of GA (0.579±0.184) and group U0126 (0.249±0.082) and the expressions of p-p38 MAPK were much lower in 100 μg/ml concentrations of GA (0.445±0.081) and group SB203580 (0.249±0.082) compared with those in group CD3 (1.028±0.147, 0.902±0.107) (all P <0.05). Conclusion: ERK1/2 and p38 MAPK signaling pathways are activated in asthmatic mice and GA may negative regulate this activation.