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eCAM Advance Access published online on July 29, 2009
eCAM, doi:10.1093/ecam/nep088
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© 2009 The Author(s).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

S-Petasin, the Main Sesquiterpene of Petasites formosanus, Inhibits Phosphodiesterase Activity and Suppresses Ovalbumin-induced Airway Hyperresponsiveness

Chung-Hung Shih1, Tzu-Jung Huang2, Chien-Ming Chen3, Yun-Lian Lin4 and Wun-Chang Ko2

1Department of Internal Medicine, Taipei Medical University Hospital, 2Graduate Institute of Pharmacology, 3Department of Medical Technology, College of Medicine, Taipei Medical University and 4National Research Institute of Chinese Medicine, Taipei, Taiwan

S-Petasin is the main sesquiterpene of Petasites 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 IC50 and Ki values 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)-{alpha} and interferon (IFN)-{gamma} 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 IgG2a level in serum of these mice. The PDE4H value of S-petasin was >300 µM; therefore, its PDE4H/PDE4L value was calculated to be >17. In conclusion, the present results for S-petasin at least partially explain why Petasites formosanus is used as a folk medicine to treat asthma in Taiwan.

Keywords: airway hyperresponsiveness – allergic asthma – cytokines – PDE4H/PDE4L ratio – phosphodiesterase 3/4 inhibitor – S-petasin

For reprints and all correspondence: Wun-Chang Ko, Graduate Institute of Pharmacology, College of Medicine, Taipei Medical University, 250 Wu-Hsing St., Taipei 110, Taiwan. Tel: +886-2-2736-1661 ext 3197; Fax: +886-2-2377-7639; E-mail: wc_ko{at}tmu.edu.tw

Received March 30, 2009; accepted June 15, 2009


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