Biflavonoid-rich fraction from Daphne pseudomezereum var. koreana Hamaya exerts anti-inflammatory effect in an experimental animal model of allergic asthma.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE Daphne pseudomezereum var. koreana Hamaya is distributed in the Gangwon-do of South Korea and is traditionally used to treat chronic inflammatory diseases, including rheumatoid arthritis. AIM OF THE STUDY We investigated the anti-inflammatory effect of biflavonoid-rich fraction (BF) obtained from an extract of D. pseudomezereum leaves on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and mouse model of ovalbumin (OVA)-induced allergic asthma. MATERIALS AND METHODS: Neochamaejasmin B (NB) and chamaejasmin D (CD) were spectroscopically characterized as major components of BF obtained from the leaves of D. pseudomezereum. RAW264.7 cells pretreated with NB, CD and BF and activated by LPS (500 ng/ml) were used to assess the anti-inflammatory effects of these materials in vitro. To evaluate the protective effect of BF on allergic asthma, female BALB/c mice were sensitized to OVA by intraperitoneal (i.p.) injection and treated with BF by oral administration (15 or 30 mg/kg). RESULTS: Pretreatment with BF inhibited LPS-stimulated nitric oxide (NO), TNF-α and IL-6, and led to upregulation of heme oxygenase-1 (HO-1) in RAW264.7 macrophages. Orally administered BF significantly inhibited the recruitment of eosinophils and the production of IL-5, IL-6, IL-13 and MCP-1 as judged by the analysis of BALF from OVA-induced asthma animal model. BF also decreased the levels of IgE in the serum of asthmatic mice. BF suppressed the influx of inflammatory cells into nearby airways and the hypersecretion of mucus by the airway epithelium of asthmatic mice. In addition, the increase in Penh in asthmatic mice was reduced by BF administration. Furthermore, BF led to Nrf2 activation and HO-1 induction in the lungs of mice. CONCLUSIONS: These data have shown the anti-asthmatic effects of BF, and therefore we expect that BF may be a potential candidate as a natural drug/nutraceutical for the prevention and treatment of allergic asthma.