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.