Treatment With Quercetin Attenuates The Development Of Pulmonary Fibrosis

Background and Objective: Pulmonary fibrosis is a serve end-stage disorder for which efficacious therapeutic options are not easily available and has a high mortality in patients with it. Although the pathogenesis of pulmonary fibrosis is poorly understood, many studies suggested that the initial inflammation and various cytokines which regulated by nuclear factor kappa B(NF-kB) played an important role in it. Quercetin (3,3,4,5,7-pentahydroxy flavone) is a flavonoid phpytoestrogen that occurs ubiquitously in plants. Quercetin has a variety of biological effects such as anti-inflammation and antioxidant and has no obvious toxic side effect. Recently, it's reported that quercetin also had anti-fibrosis property in vivo and in vitro. Although the mechanisms of anti-fibrosis effect of quercetin are still unclear, it's believed that it is associated with its anti-inflammation and antioxidant biological effects. In our study, the PEG-PE liposomal quercetin were injected by intraperitoneally (i.p) to the mice which received intratracheal administration of bleomycin. The inhibitions of liposomal quercetin on bleomycin induced pulmonary fibrosis were investigated. And, to explore the possible mechanism of anti-fibrosis of quercetin, we analysed the expression level of NF-kB using real-time RT-PCR.Methods: Mice were injected intraperitoneally with PEG-PE liposomal quercetin or saline. One day after the treatment with PEG-PE liposomal quercetin or saline, these mice were administrated bleomycin or saline intratracheally. 7 days after bleomycin or saline administration, the lungs were lavaged with PBS to get the BALF and the counts of cell in BALF were analysed. Mice were sacrificed 28 days after bleomycin or saline administration. The lungs were removed to assess the hydroxyproline in quantitation and H&E staining of lung was performed. The expression level of NF-κB was analysed by real-time RT-PCR on 7 days after bleomycin or saline administration and the survival of mice during this period was recorded.Results: In the model of bleomycin induced pulmonary fibrosis, liposomal quercetin reduced the number of macrophages, lymphocytes and netruophils in the initial inflammation of bleomycin induced. The smaller width of fibrous thickening of alveolar and bronchiolar wall and the limited area of fibrosis in lungs after bleomycin administration were observed in mice treated with liposomal quercetin compared with untreated or treated with null-liposome. In the model of bleomycin induced pulmonary fibrosis, liposomal quercetin reduced the the expression level of hydroxyproline. The mice treated with liposomal quercetin demonstrated a prolonged survival (median survival time: 28days , p<0.05) compared with control mice treated with null-liposome (18days) and saline (17days). Finally, real-time RT-PCR indicated that lipisomal quercetin can reduce the expression level of NF-kB in bleomycin induced pulmonary fibrosis.Conclusion: This study demonstrates that lipisomal quercetin injected byintraperitoneally can suppress bleomycin-induced acute pulmonaryinflammation and thus attenuate the development of pulmonary fibrosispossibly by regulating the expression level of NF-kB.