Anti-asthmatic effect of laurotetanine extracted from Litsea cubeba (Lour.) Pers. root on ovalbumin-induced allergic asthma rats, and elucidation of its mechanism of action

Abstract

Purpose: To investigate the anti-asthmatic effect of laurotetanine on allergic asthma rat model. Methods: Laurotetanine was extracted from the roots of Litsea cubeba (Lour.) Pers. Asthma was induced in rats by ovalbumin injection. Laurotetanine (20, 40, or 60 mg/kg) was administered orally to the rats for 21 days. Inflammatory cells and cytokines released by T-cell subsets Th1 and Th2 in the bronchoalveolar lavage fluid were determined. Serum immunoglobulin E (IgE) and histamine, in addition to expression of mucin 5AC (MUC-5AC), nuclear factor-kappa B (NF-κB), and an inhibitor of NF-κB (IκB) in lung tissues were also evaluated. Results: Laurotetanine treatment (20, 40, 60 mg/kg) significantly reduced inflammatory cells, including eosinophils, neutrophils, lymphocytes, and macrophages in treated rats compared with control animals (p < 0.01). Inflammatory cytokines, viz, interleukin (IL) -4, IL-6, IL-13 were also significantly (p < 0.01) decreased by laurotetanine treatment (20, 40, 60 mg/kg), whereas interferon gamma (IFN-γ) was increased (p < 0.01). Serum IgE and histamine were significantly reduced (p < 0.01) by laurotetanine (20, 40, 60 mg/kg). Furthermore, MUC5AC expression in lung tissues was significantly (p < 0.01) downregulated by laurotetanine (20, 40, and 60 mg/kg, but NF-κB and IκB were significantly (p < 0.01) upregulated by laurotetanine (20, 40, and 60 mg/kg). Conclusion: Laurotetanine exerts an anti-asthmatic effect in rats by inhibition of IgE, histamine, and inflammatory reactions via down-regulating MUC5AC and NF-κB signaling pathways. This finding justifies the need for further development of laurotetanine as a potential anti-asthmatic drug.