Rutin decreases lipopolysaccharide-induced acute lung injury via inhibition of oxidative stress and the MAPK-NF-κB pathway.
Acute lung injury (ALI) is a serious disease with unacceptably high mortality and morbidity rates. Up to now, no effective therapeutic strategy for ALI has been established. Rutin, quercetin-3-rhamnosyl glucoside, expresses a wide range of biological activities and pharmacological effects, such as anti-inflammatory, antihypertensive, anticarcinogenic, vasoprotective, and cardioprotective activities. Pretreatment with rutin inhibited not only histopathological changes in lung tissues but also infiltration of polymorphonuclear granulocytes into bronchoalveolar lavage fluid in lipopolysaccharide (LPS)-induced ALI. In addition, LPS-induced inflammatory responses, including increased secretion of proinflammatory cytokines and lipid peroxidation, were inhibited by rutin in a concentration-dependent manner. Furthermore, rutin suppressed phosphorylation of NF-κB and MAPK and degradation of IκB, an NF-κB inhibitor. Decreased activities of antioxidative enzymes such as superoxide dismutase, catalase, glutathione peroxidase, and heme oxygenase-1 caused by LPS were reversed by rutin. At the same time, we found that ALI amelioration by chelation of extracellular metal ions with rutin is more efficacious than with deferoxamine. These results indicate that the protective mechanism of rutin is through inhibition of MAPK-NF-κB activation and upregulation of antioxidative enzymes.
Department of Neurology, Show Chwan Memorial Hospital, Changhua, Taiwan; Department of Nursing, College of Medicine & Nursing, Hung Kuang University, Taichung, Taiwan.
Chung-Hsin
CH
Yeh
Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan.
Jiann-Jou
JJ
Yang
Department of Anatomy, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Ming-Ling
ML
Yang
Department of Pharmacology, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Yi-Ching
YC
Li
Department of Pharmacology, School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Pharmacy, Chung Shan Medical University Hospital, Taichung 402, Taiwan. Electronic address: kuanyh@csmu.edu.tw.
Yu-Hsiang
YH
Kuan
D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics; D000818:Animals; D002374:Catalase / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000096:biosynthesis; D051547:Heme Oxygenase-1 / Q000096:biosynthesis; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects*; D012431:Rutin / Q000008:administration & dosage* / Q000633:toxicity; D015398:Signal Transduction / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000096:biosynthesis; D000072105:Superoxide Dismutase-1
D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606290:SOD1 protein, human; D012431:Rutin; D002374:Catalase; D005979:Glutathione Peroxidase; D051547:Heme Oxygenase-1; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D020929:Mitogen-Activated Protein Kinase Kinases
Acute lung injury; CAT; Free radicals; GPx; HO-1; Lipopolysaccharide; MAPK; NF-κB; Rutin; SOD