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.
Highlights
Allergic asthma is a common, intractable, allergyrelated airway disease that is seriously affecting the quality of life of millions people of all ages around the world [1,2]
Structural characteristics of laurotetanine extracted from Litsea cubeba Our results indicate that the purity of laurotetanine was > 98 % based on HPLC analysis using area normalization method (Figure 2)
The spectra of 1H-NMR and 13CNMR of laurotetanine shown in Table 1 are in good agreement with the reported literature data for laurotetanine [8,10]
Summary
Allergic asthma is a common, intractable, allergyrelated airway disease that is seriously affecting the quality of life of millions people of all ages around the world [1,2]. (L. cubeba) has been used as a folk herbal medicine to treat asthma, RA, and other inflammatory disorders for many years in China [8,9]. The present study was designed to explore the anti-asthmatic properties and mechanism of action of laurotetanine in ovalbumin (OVA)-induced allergic asthmatic rats to advance the development of this compound as a novel anti-asthmatic drug. The roots of L. cubeba were acquired from the Tongren drug store (Harbin, China). Fr.Et4 was further separated with repeated silica gel (200–300 mesh) column chromatography elutions using PE:EtOAc, at a ratio of 7:1, to afford the pure target compound laurotetanine. To induce asthma in rats, animals were treated with a mixture of 50 mg of OVA and 2 mg of aluminum hydroxide by intraperitoneal injection (ip) on the 1st and 14th days of the experiment. All the data are represented as mean ± standard deviation, and a p value of less than 0.05 was considered significant
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