Objective: To observe the effects of astragaloside IV on the airway remodeling and the expressions of transforming growth factor (TGF)-β1 and thymic stromal lymphopoietin (TSLP) in a murine model of asthma.
Methods: Forty-eight BALB/c mice were randomly divided into 4 groups, i.e. control group, asthma group, astragaloside IV group and budesonide group (n = 12 each). The BALB/c mice sensitized to ovalbumin (OVA) were chronically challenged with aerosolized OVA for 8 weeks while the mice in the astragaloside IV group were intragastrically administered with astragaloside IV (50 mg/kg) daily for 8 consecutive weeks. Pulmonary functions were measured to evaluate the resistance of expiration. And pulmonary histopathological analysis was performed to observe the infiltration of inflammatory cells, the hyperplasia of airway global cells and the deposition of collagen. The levels of interleukin (IL)-4 and IL-13 in bronchoalveolar lavage fluid (BALF) were measured by ELISA (enzyme linked immunosorbent assay). The pulmonary expression of α-SMA (alpha-smooth muscle actin) was evaluated by immunohistochemistry. The mRNA and protein expressions of TGF-β1 and TSLP were measured by real-time PCR (polymerase chain reaction) and Western blot respectively.
Results: The treatment of astragaloside IV or budesonide led to a sharp decrease in airway resistance compared with the asthma group at a concentration of acetylcholine in 30 µg/kg (P < 0.05). The PAS(+) epithelial/bronchial epithelial cells, the area of collagen staining and α-SMA staining area were significantly elevated in the asthma group compared with the control group (all P < 0.01) while those in the astragaloside and budesonide groups were obviously inhibited compared with the asthma group (all P < 0.05). The BALF levels of IL-4 and IL-13 were markedly elevated in the asthma group versus the control group (P < 0.01) while those markedly decreased in the astragaloside and budesonide groups versus the asthma group (all P < 0.05). The relative expressions of TGF-β1 and TSLP mRNA (5.23 ± 1.44, 5.70 ± 1.65) were significantly up-regulated in the asthma group versus the control group (1.02 ± 0.21, 1.02 ± 0.25) (P < 0.01) while those in the astragaloside (2.27 ± 0.65, 2.97 ± 1.03) and budesonide groups (2.10 ± 0.57, 3.32 ± 1.11) were obviously down-regulated versus the asthma group (all P < 0.05). The protein levels of TGF-β1 and TSLP in the asthma group (0.89 ± 0.11, 0.74 ± 0.10) were markedly elevated versus the control (0.39 ± 0.04, 0.44 ± 0.05), the astragaloside (0.51 ± 0.08, 0.59 ± 0.12) and the budesonide groups (0.55 ± 0.08, 0.60 ± 0.08) (all P < 0.05).
Conclusion: Astragaloside IV can suppress the progression of airway inflammation, airway hyperresponsiveness and remodeling in a murine model of asthma. The above effects may be partially due to the inhibited expressions of TGF-β1 and TSLP.