Immune-modulatory effects of bu-zhong-yi-qi-tang in ovalbumin-induced murine model of allergic asthma

Abstract

Background: Bu-zhong-yi-qi-tang (BZYQT), an herbal formula of traditional Chinese medicine, has been an effective regimen of allergic diseases for nearly 800 years. Our previous report has demonstrated its anti-inflammatory effects in patients with perennial allergic rhinitis, and the aim of this study is to investigate the anti-asthmatic effect of BZYQT.

Methods: Female BALB/cByJNarl mice were sensitized with normal saline (control group) or OVA. Mice sensitized by OVA were fed with distilled water (OVA group), oral 0.5 g/Kg (low-dose group) or 1 g/Kg (high-dose group) of BZYQT solution once daily on days 36-40 besides their routine diet. Airway hyper-responsiveness (AHR), eosinophil infiltration, levels of cytokines and total immunoglobulin E (IgE) in broncho-alveolar lavage fluid (BALF) were determined. The lungs and tracheas were removed, and histopathologic examination was subsequently performed.

Results: AHR was significantly reduced in both low- and high-dose BZYQT groups compared with the OVA group after inhalation of the highest dose of methacholine (50 mg/ml). The levels of eotaxin, Th2-related cytokines (IL-4, IL-5, IL-13), IgE, and eosinophil infiltration in BALF were significantly decreased in both BZYQT groups compared with the OVA group. Histopathologic examination revealed that eosinophil infiltration of the lung and trachea tissues was remarkably attenuated in both BZYQT groups.

Conclusions: Oral administration of BZYQT solution may exert anti-asthmatic effect by relieving AHR in OVA-sensitized mice, which is compatible with our clinical experience. Although detailed mechanism is to be determined, we surmise that it may be correlated with the immune-modulatory effects of inhibiting Th2 responses on the basis of our limited results.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. HPLC data of Bu-Zhong-Yi-Qi-Tang (BZYQT) (Upper: BZYQT; Lower: standard sample).

The peaks indicate the existence of glycyrrhizin, AHB, Ferulic acid, and MPB in both panels, which proves the authenticity of BZYQT.

Fig 2. Effect of oral administration of BZYQT on airway hyperresponsiveness (AHR).

After last OVA challenge, mice were exposed to a series of incremental dosages of methacholine (6.25, 12.5, 25, 50 mg/ml). The Penh values were then recorded, indicating AHR of mice under each dosage of methacholine stimulation. Control group (●, n = 10), OVA group (○, n = 4), Low dose (0.5 g/Kg) BZYQT group (△, n = 8), High dose (1 g/Kg) BZYQT group (▼, n = 8). Data were presented in mean ± standard deviation. ** p

Fig 3. BZYQT regulated Th2 cytokines in BALF of asthmatic murine model sensitized by OVA.

The concentrations of IL-4 (A), IL-5 (B), and IL-13 (C) were determined by ELISA. Data were presented in mean ± standard deviation. * p

Fig 4. BZYQT significantly attenuated IgE levels in BALF of OVA-sensitized mice.

These data were measured by ELISA, and presented in mean ± standard deviation. ** p

Fig 5. The concentration of eosinophil chemoattractant eotaxin (B) and the percentage of eosinophil cell count (A) in BALF were significantly down-regulated in the BZYQT groups.

Data were presented in mean ± standard deviation. * p

Fig 6. Histopathologic examination of sections of lung and trachea tissues with H&E stain.

Specimens were derived from the control (low power view, A; high power view, B), OVA (low power view, C; high power view, D), LD (low power view, E; high power view, F), and HD (low power view, G; high power view, H) groups, respectively. Notably, eosinophil infiltration over the perivascular and peribronchiolar areas were enhanced in OVA group, and then attenuated in both BZYQT groups significantly.