Immunoregulatory Effects of Paeoniflorin Exerts Anti-asthmatic Effects via Modulation of the Th1/Th2 Equilibrium

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Immunoregulatory Effects of Paeoniflorin Exerts Anti-asthmatic Effects via Modulation of the Th1/Th2 Equilibrium Tianzhu Zhang,1 Zhaocong Yang,2 Shihai Yang,3 Juan Du,4 and Shumin Wang1,5

Abstract—Paeoniflorin has been demonstrated to exert anti-inflammatory and immunomodulatory effects in the animal study. In this study, we investigated immunoregulatory effects of paeoniflorin on anti-asthmatic effects and underlying mechanisms. Asthma model was established by ovalbumininduced. A total of 50 mice were randomly assigned to five experimental groups: control, model, dexamethasone (2 mg/kg), and paeoniflorin (10 and 20 mg/kg). Airway resistance (Raw) were measured by the forced oscillation technique; histological studies were evaluated by the hematoxylin and eosin (HE) staining; Th1/Th2 cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA); Th1/Th2 cells were evaluated by flow cytometry (FCM); and GATA3 and T-bet were evaluated by Western blot. Our study demonstrated that, compared with model group, paeoniflorin inhibited ovalbumin (OVA)-induced increases in Raw and eosinophil count; interleukin (IL)-4, IgE levels were recovered in bronchoalveolar lavage fluid compared; increased IFN-γ level in bronchoalveolar lavage fluid; histological studies demonstrated that paeoniflorin substantially inhibited OVA-induced eosinophilia in lung tissue and lung tissue compared with model group. Flow cytometry studies demonstrated that paeoniflorin can regulate Th1/Th2 balance. These findings suggest that paeoniflorin may effectively ameliorate the progression of asthma and could be used as a therapy for patients with allergic asthma. KEY WORDS: paeoniflorin; anti-asthmatic; Th1/Th2; GATA3/T-bet.

INTRODUCTION Allergic diseases of the airway such as asthma or allergic rhinitis are on the rise throughout the world, especial in western countries [1]. One of the most important diseases is bronchial asthma that is defined as a chronic inflammation of the bronchial airways and characterized by reversible airway obstruction, increased mucus production and infiltration of the airway with eosinophils, neutrophils, mast cells, and T-lymphocytes [2]. Type 1 allergies are caused by characteristic immune responses to allergens, primarily mediated by Th2 cells. Th2 cells synthesize high levels of interleukin IL-4, IL-5, and Tianzhu Zhang and Zhaocong Yang contributed equally to this work. 1

Changchun University of Chinese Medicine, Changhcun, 130117, China Nanjing University of Chinese Medicine, Nanjing, China 3 Jilin Agricultural University, Changchun, 130118, China 4 School of Life Science, Peking University, Beijing, China100871 5 To whom correspondence should be addressed at Changchun University of Chinese Medicine, Changhcun, 130117, China. E-mail: [email protected] 2

IL-13, which leads to the production of allergenspecific immunoglobulin (Ig) E and the release of mediators from mast cells [3]. Th1 cells suppress Th2 immune responses by secreting interferon IFNγ. IL-4 induces class switching in IgG1 and IgE, whereas IFN