Effect of artesunate on airway responsiveness and airway inflammation in asthmatic mice

Abstract

Objective: To observe the effects of artesunate on airway responsiveness and airway inflammation in asthmatic mice. Methods: Thirty female BALB/c mice aged 6-8 weeks were randomly divided into control group, asthma group and artesunate group. In the asthma group and the artesunate group, the mice were sensitized by intraperitoneal injection of 20 μg of ovalbumin (OVA) and 0.2 ml of aluminum hydroxide suspension (2 mg) on day 0 and 14, respectively, and 1% OVA 10 ml dissolved in sterile phosphate (PBS) buffer was aerosolized for 30 min from the 21st to 28th day. The control group was sensitized with 0.2 ml of 2 mg suspension of aluminum hydroxide on day 0 and 14, and aerosolized by 10 ml of sterile PBS from the 21st to 28th day. Before the challenge, the artesunate group was intraperitoneally injected with 0.2 ml of artesunate. Artesunate was replaced with the same amount of normal saline in the control group and the asthma group. The mice were treated after 24 hours of last stimulation. The airway responsiveness of mice was measured by airway intubation and the changes of airway resistance and compliance were observed. Bronchoalveolar lavage fluid (BALF) was classified by cytology, and pathological changes of left lung tissue were observed and scored. Results: The airway resistance of the three groups increased and the lung compliance decreased with the increase of methacholine (Ach) concentration. The airway resistance and lung compliance of the three groups were different under the same concentration (P<0.05). The airway resistance of the artesunate group at Ach 6.25, 12.5, 25, 50, 100 mg/ml was lower than that of the asthma group at the same concentration [(1.01±0.48) vs (1.30±0.22), (1.06±0.44) vs (1.70±0.31), (1.30±0.64) vs (2.66±0.79), (1.82±0.55) vs (3.38±1.35), (2.49±0.85) vs (4.07±1.34) cmH(2)O·s(-1)·ml(-1)(1 cmH(2)O=0.098 kPa); t=3.862, 7.376, 9.113, 7.051, 6.685, all P<0.05]; the degree of lung compliance decrease at the concentration of Ach 3.125, 6.25, 12.5, 25, 50, 100 mg/ml was lower than that of the asthma group at the same concentration [(3.89±0.55)×10(-2) vs (3.07±0.63)×10(-2), (3.61±0.52)×10(-2) vs (3.04±0.58)×10(-2), (3.48±0.38)×10(-2) vs (2.78±0.57)×10(-2), (3.09±0.52)×10(-2) vs (1.73±0.62)×10(-2), (2.32±0.60)×10(-2) vs (1.29±0.54)×10(-2), (1.87±0.59)×10(-2) vs (1.15±0.44)×10(-2) ml/cmH(2)O; t=-6.295, -4.921, -6.533, -11.135, -8.48, -6.319, all P<0.05]. The proportion of eosinophils in artesunate group in BALF was significantly lower than that in asthma group [(16.63±8.58)% vs (40.44±12.94)%; t=4.336, P<0.05]. In the asthma group, the inflammatory cells infiltration of the bronchi and the perivascular area, the bronchial epithelial edema and degeneration can be observed, and the artesunate could reduce the infiltration of inflammatory cells around the bronchus and blood vessels, and the mucus secretion was also reduced in the artesunate group. Conclusion: Artesunate can improve airway hyperresponsiveness and airway inflammation in asthmatic mice and has a certain therapeutic effect on asthma.