Prevention of Lung Inflammation by Isoflavone Genistein
Susan W.S. Leung1, Pang Zhang1,2, Jenny K.W. Lam1 & Judith C.W. Mak1,3
1Department of Pharmacology and Pharmacy, University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China
2Department of Pharmacy, Luohu People’s Hospital, 47 Youyi Road, Luohu, Shenzhen, 518001, China
3Department of Medicine, University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China
Summary
Genistein is a natural product present in the diet, and appears to possess many biological actions including anti-inflammatory, anti-oxidant, anti-microbial, estrogenic/anti-estrogenic and vasodilatory activities. As such, it is likely to be useful as a preventive/therapeutic agent against inflammatory responses in the lung caused by bacterial/viral infection. The present study aimed to determine the effects of genistein in the lung exposed to inflammatory insults. Male Sprague Dawley rats (eight-week old) were administered with either genistein (10-2 g/kg) or its vehicle (methylcellulose, 0.5%) by oral gavage once every day for eight weeks, and with bacterial endotoxin lipopolysaccharides (LPS; 2´10-4 g/kg) or its vehicle (sterile saline) intratracheally using a microsprayer at day 28 and day 42 during genistein/vehicle treatment. Exposure to airborne LPS resulted in alveolar enlargement; this is associated with increased levels of inflammatory mediators [interleukin (IL)-6, CINC-1 (resemble to human IL-8) and monocyte-chemotactic protein-1] in the bronchoalveolar lavage fluid, and of the oxidative stress marker malondialdehyde in the lung lysates. These effects of LPS were reduced in rats treated with genistein. Moreover, genistein prevented the LPS-induced increased activity of the anti-oxidant enzyme catalase in the lungs. The present findings, therefore, demonstrated a protective effect of genistein against the induction of lung inflammation by airborne LPS. Taken into consideration of the multiple systemic biological actions, and the variable pharmacokinetic profile of orally-administered genistein, the development of inhalable formulation or pulmonary delivery approaches is warranted in order for genistein to be useful as a preventive/therapeutic agent against lung inflammation.
Key Message
Genistein is effective in protecting the airway against oxidative stress and inflammatory responses caused by airborne LPS exposure; therefore, the development of inhalation formulation or pulmonary delivery approaches for genistein would permit the safe and effective use of this isoflavone to prevent/manage the pulmonary inflammation caused by different pathologies.