Antagonistic effects of nobiletin, a polymethoxyflavonoid, on eosinophilic airway inflammation of asthmatic rats and relevant mechanisms.

Abstract

Eosinophils are known to be the important effector cells in asthmatic airway inflammation. The purpose of this study was to investigate the effects of nobiletin, a polymethoxyflavonoid, on eosinophilic airway inflammation of asthmatic rats, and explore its possible mechanisms. Animals were actively sensitized by subcutaneous injection of ovalbumin (OVA). The inflammation in lung tissues of asthmatic rats was observed by hematoxylin and eosin (HE) staining. The eosinophils in blood and BALF were separated by Percoll density gradient centrifugation and counted under microscope. The level of Eotaxin was detected by enzyme-linked immunosorbent assay (ELISA). In addition, the apoptosis of eosinophils was labeled by TdT-mediated dUTP nick end labeling (TUNEL) technique, the semi-quantitative detection for Fas mRNA expression of eosinophils was performed by reverse transcription-polymerase chain reaction (RT-PCR). The airway inflammation of asthmatic rats pretreated with nobiletin was obviously alleviated. Nobiletin (1.5 and 5.0 mg/kg given intraperitoneally) significantly reduced OVA-induced increases in eosinophils, remarkably lowered the level of Eotaxin in blood and broncho-alveolar lavage fluid (BALF) of asthmatic rats. On the other hand, semi-quantitative RT-PCR analysis for Fas of eosinophils from OVA aerosol-challenged sensitized rats showed that Fas mRNA expression of eosinophils was obviously enhanced by nobiletin. Meanwhile, the apoptosis index of cultured eosinophils was significantly elevated after treatment with different doses of nobiletin. These results indicated that nobiletin could inhibit the eosinophilic airway inflammation. Lowering the levels of Eotaxin, relieving airway infiltration of eosinophils and promoting apoptosis of eosinophils by enhancing expression of Fas mRNA may be important mechanisms for nobiletin to antagonize eosinophilic airway inflammation of asthmatic rats.

• Authors: Yu-Qing Wu, Cheng-Hua Zhou, Jin Tao, Sheng-Nan Li
• Journal: Life sciences (Life Sci) Vol. 78 Issue 23 Pg. 2689-96 (May 01 2006) ISSN: 0024-3205 [Print] Netherlands
• PMID: 16337971 (Publication Type: Journal Article)

Chemical References

• Anti-Asthmatic Agents
• Antioxidants
• Ccl11 protein, rat
• Chemokine CCL11
• Chemokines, CC
• Flavones
• RNA, Messenger
• fas Receptor
• Ovalbumin
• nobiletin

Topics

• Animals
• Anti-Asthmatic Agents (therapeutic use)
• Antioxidants (therapeutic use)
• Apoptosis (drug effects)
• Asthma (chemically induced, drug therapy, pathology)
• Bronchitis (chemically induced, drug therapy, pathology)
• Bronchoalveolar Lavage Fluid (cytology)
• Chemokine CCL11
• Chemokines, CC (blood)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Eosinophils (drug effects, pathology)
• Flavones (therapeutic use)
• Injections, Intraperitoneal
• Male
• Ovalbumin
• RNA, Messenger (metabolism)
• Rats
• Rats, Sprague-Dawley
• fas Receptor (genetics, metabolism)