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Evidence-Based Complementary and Alternative Medicine
Volume 2012, Article ID 472897, 10 pages
Research Article

Hesperetin, a Selective Phosphodiesterase 4 Inhibitor, Effectively Suppresses Ovalbumin-Induced Airway Hyperresponsiveness without Influencing Xylazine/Ketamine-Induced Anesthesia

1Department of Internal Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan
2Department of Dentistry, Taipei Medical University Hospital, Taipei 110, Taiwan
3Department of Otolaryngology, Taipei Medical University Hospital, Taipei 110, Taiwan
4Department of Dermatology, Taipei Medical University Hospital, Taipei 110, Taiwan
5Department of Pharmacology, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan
6Department of Medical Technology, College of Medicine, Taipei Medical University, Taipei 110, Taiwan

Received 18 June 2011; Accepted 5 November 2011

Academic Editor: Xiu-Min Li

Copyright © 2012 Chung-Hung Shih et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Hesperetin, a selective phosphodiesterase (PDE)4 inhibitor, is present in the traditional Chinese medicine, “Chen Pi.” Therefore, we were interested in investigating its effects on ovalbumin- (OVA-) induced airway hyperresponsiveness, and clarifying its rationale for ameliorating asthma and chronic obstructive pulmonary disease (COPD). Hesperetin was revealed to have a therapeutic (PDE4H/PDE4L) ratio of >11. Hesperetin (10 ~ 30 μmol/kg, intraperitoneally (i.p.)) dose-dependently and significantly attenuated the airway hyperresponsiveness induced by methacholine. It also significantly suppressed the increases in total inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils, and levels of cytokines, including interleukin (IL)-2, IL-4, IL-5, interferon-γ, and tumor necrosis factor-α in bronchoalveolar lavage fluid (BALF). It dose-dependently and significantly suppressed total and OVA-specific immunoglobulin E levels in the BALF and serum. However, hesperetin did not influence xylazine/ketamine-induced anesthesia, suggesting that hesperetin has few or no emetic effects. In conclusion, the rationales for ameliorating allergic asthma and COPD by hesperetin are anti-inflammation, immunoregulation, and bronchodilation.