Hesperetin-5,7,3ʹ-o-trimethylether dually inhibits phosphodiesterase 3/4 and methacholine-induced airway hyperresponsiveness in sensitized and challenged mice

Chung Hung Shih, Wen Hung Wang, Chi Ming Chen, Wun Chang Ko

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Introduction: Hesperetin-5,7,3ʹ-O-trimethylether (HTME), a synthetic liposoluble hesperetin, has been reported to be a dual phosphodiesterase (PDE)3/4 inhibitor. We investigated its inhibitory effects on methacholine (MCh)-induced airway hyperresponsiveness (AHR) and its potential for treating atypical asthma and COPD. Methods: FlexiVent system was used to determine AHR in ovalbumin (OVA) sensitized and challenged mice. Determination of cytokines was performed by using mouse T helper (Th)1/Th2 cytokine CBA kits, and of total immunoglobulin (Ig)E and OVA-specific IgE using ELISA kits. The number of inflammatory cells was counted using a hemocytometer. Xylazine/ketamine-induced anesthesia was to assess nausea, vomiting, and gastric hypersecretion in these mice. Results: HTME dually and competitively inhibited PDE3/4 activities in the Lineweaver– Burk analysis. HTME (30 and 100 μmol/kg) dose-dependently and significantly decreased the airway resistance (RL) and increased lung dynamic compliance (Cdyn) values induced by MCh. It significantly suppressed numbers of total inflammatory cells and neutrophils, and levels of cytokines in bronchoalveolar lavage fluid (BALF). HTME dose-dependently and significantly inhibited total and OVA-specific IgE levels in the BALF and serum. However, HTME did not influence xylazine/ketamine-induced anesthesia. Conclusion: HTME exerted anti-inflammatory and bronchodilator effects and may be useful in treating chronic obstructive pulmonary disease and allergic atypical asthma with no gastrointestinal side effects.

Original languageEnglish
Pages (from-to)519-526
Number of pages8
JournalDrug Design, Development and Therapy
Volume14
DOIs
Publication statusPublished - 2020

Keywords

  • Allergic asthma
  • Bronchoalveolar lavage fluid
  • Chronic obstructive pulmonary disease
  • Cytokines
  • Inflammation
  • Ovalbumin
  • Therapeutic PDE4/PDE4 ratio

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery

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