title: Oroxylin A attenuates cigarette smoke-induced lung inflammation by activating Nrf2.
abstract: Oroxylin A, a natural flavonoid isolated from the medicinal herb Scutellaria baicalensis Georgi, has been reported to have anti-inflammatory and antioxidant properties. However, the effect of oroxylin A on cigarette smoke (CS)-induced lung inflammation remains unclear. In this study, the ability of oroxylin A to protect against CS-induced lung inflammation was detected in vivo and in vitro. Oroxylin A was administered intraperitoneally to mice 2h prior CS exposure every day for five consecutive days. BEAS-2B bronchial epithelial cells and RAW264.7 cells were used to investigate the molecular mechanism of oroxylin A in vitro. In vivo, the results showed that oroxylin A dose-dependently attenuated CS-induced lung histopathologic changes, expression of cytokines TNF-α, IL-1β, and MCP-1, and levels of oxidative biomarkers 3-nitrotyrosine and 8-isoprostane. Meanwhile, oroxylin A up-regulated GSH level and glutathione reductase (GR) activity in lung tissues. In vitro, oroxylin A significantly up-regulated Nrf2 expression and total cellular glutathione level in cigarette smoke extract (CSE)-stimulated cells. In addition, oroxylin A promoted Nrf2 binding to antioxidant response element (ARE) and up-regulated ARE-regulated gene such as heme oxygenase-1 (HO-1), GPx, and GR in CSE-stimulated cells. Oroxylin A could protect both epithelial cells and macrophages from damage by cigarette smoke in vitro. Taken together, these data indicated that oroxylin A attenuated oxidative stress and lung inflammation induced by CS via activating Nrf2 signaling pathway. Oroxylin A may be a protective agent against CS-induced lung inflammation and chronic obstructive pulmonary disease.
authors.affiliation: Department of Emergency, The Second Affiliated Hospital of Harbin Medical University, China.
authors.forename: Jihe
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Harbin Medical University, China.
authors.forename: Dongxia
authors.initials: D
authors.lastname: Tong
authors.affiliation: Department of Hematology, The Second Affiliated Hospital of Harbin Medical University, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Stomatology, The Second Affiliated Hospital of Harbin Medical University, China.
authors.forename: Fuyang
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Vascular Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, China. Electronic address: shenyongbin11@sina.com.
authors.forename: Yongbin
authors.initials: Y
authors.lastname: Shen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology; D005419:Flavonoids / Q000627:therapeutic use*; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy*; D000067996:RAW 264.7 Cells; D031364:Scutellaria baicalensis / Q000276:immunology*; D012907:Smoking / Q000009:adverse effects; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005419:Flavonoids; D018836:Inflammation Mediators; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; C080669:5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
keywords: Cigarette smoke; Nrf2; Oroxylin A