Icariin Ameliorates Cigarette Smoke Induced Inflammatory Responses via Suppression of NF-κB and Modulation of GR In Vivo and In Vitro

• Published in: PloS one Vol. 9; no. 8; p. e102345
• Main Authors: Li, Lulu, Sun, Jing, Xu, Changqing, Zhang, Hongying, Wu, Jinfeng, Liu, Baojun, Dong, Jingcheng
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 04.08.2014; Public Library of Science (PLoS)
• Subjects: Airway management; Animal models; Animals; Asthma; Biology and Life Sciences; Cell Line, Tumor; Chronic illnesses; Chronic obstructive pulmonary disease; Cigarette smoke; Cigarette smoking; Cigarettes; Critical care; Dexamethasone; Exposure; Flavonoids; Flavonoids - chemistry; Flavonoids - pharmacology; Gelatinase B; Gene expression; Gene Expression Regulation - drug effects; Hospitals; Humans; In vitro methods and tests; In vivo methods and tests; Inflammation; Inflammation - genetics; Inflammation - pathology; Inflammatory diseases; Inflammatory response; Interleukin 8; Interleukin-8 - metabolism; Lung - drug effects; Lung - pathology; Lung - physiopathology; Lung diseases; Lungs; Male; Matrix Metalloproteinase 9 - metabolism; Medicine; Medicine and Health Sciences; Mice; Mice, Inbred BALB C; Neutrophils; NF-kappa B - metabolism; NF-κB protein; Oxidative stress; Phosphorylation; Pulmonary functions; Receptors, Glucocorticoid - genetics; Receptors, Glucocorticoid - metabolism; Research and Analysis Methods; Respiratory function; Respiratory Function Tests; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Smoke; Smoking; Smoking - adverse effects; Synaptotagmin; Transcription factors; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; United States > US; China
• DOI: 10.1371/journal.pone.0102345
• ISSN: 1932-6203

To investigate the effects of icariin, a major constituent of flavonoids isolated from the herb Epimedium, on cigarette smoke (CS) induced inflammatory responses in vivo and in vitro. In vivo, BALB/c mice were exposed to smoke of 15 cigarettes for 1 h/day, 6 days/week for 3 months and dosed with icariin (25, 50 and 100 mg/kg) or dexamethasone (1 mg/kg). In vitro, A549 cells were incubated with icariin (10, 50 and 100 µM) followed by treatments with CSE (2.5%). We found that icariin significantly protected pulmonary function and attenuated CS-induced inflammatory response by decreasing inflammatory cells and production of TNF-α, IL-8 and MMP-9 in both the serum and BALF of CS-exposed mice and decreasing production of TNF-α and IL-8 in the supernatant of CSE-exposed A549 cells. Icariin also showed properties in inhibiting the phosphorylation of NF-κB p65 protein and blocking the degradation of IΚB-α protein. Further studies revealed that icariin administration markedly restore CS-reduced GR protein and mRNA expression, which might subsequently contribute to the attenuation of CS-induced respiratory inflammatory response. Together these results suggest that icariin has anti-inflammatory effects in cigarette smoke induced inflammatory models in vivo and in vitro, possibly achieved by suppressing NF-κB activation and modulating GR protein expression.