S-Petasin, the Main Sesquiterpene ofPetasites formosanus, Inhibits Phosphodiesterase Activity and Suppresses Ovalbumin-Induced Airway Hyperresponsiveness

Abstract

S-Petasin is the main sesquiterpene ofPetasites formosanus, a traditional folk medicine used to treat hypertension, tumors and asthma in Taiwan. The aim of the present study was to investigate its inhibitory effects on phosphodiesterase (PDE) 1–5, and on ovalbumin (OVA)-induced airway hyperresponsiveness (AHR) in a murine model of allergic asthma.S-Petasin concentration-dependently inhibited PDE3 and PDE4 activities with 50% inhibitory concentrations (IC50) of 25.5, and 17.5 μM, respectively. According to the Lineweaver-Burk analysis,S-petasin competitively inhibited PDE3 and PDE4 activities with respective dissociation constants for inhibitor binding (Ki) of 25.3 and 18.1 μM, respectively. Both IC50andKivalues for PDE3 were significantly greater than those for PDE4.S-Petasin (10–30 μmol/kg, administered subcutaneously (s.c.)) dose-dependently and significantly attenuated the enhanced pause (Penh) value induced by methacholine (MCh) in sensitized and challenged mice. It also significantly suppressed the increases in total inflammatory cells, lymphocytes, neutrophils, eosinophils and levels of cytokines, including interleukin (IL)-2, IL-4 and IL-5, tumor necrosis factor (TNF)-α and interferon (IFN)-γ in bronchoalveolar lavage fluid (BALF) of these mice. In addition,S-petasin (10–30 μmol/kg, s.c.) dose-dependently and significantly attenuated total and OVA-specific immunoglobulin E (IgE) levels in the serum and BALF, and enhanced the IgG2alevel in serum of these mice. The PDE4Hvalue ofS-petasin was >300 μM; therefore, its PDE4H/PDE4Lvalue was calculated to be >17. In conclusion, the present results forS-petasin at least partially explain whyPetasites formosanusis used as a folk medicine to treat asthma in Taiwan.