title: Osthole improves acute lung injury in mice by up-regulating Nrf-2/thioredoxin 1.
abstract: Inhibiting reactive oxygen species (ROS) has been viewed as a therapeutic target for the treatment of acute lung injury (ALI). Osthole, an active component in Chinese herbal medicine, has drawn increasing attention because of its various pharmacological functions, including anti-inflammatory and anti-oxidative activities. The aim of the present study was to examine the effects of osthole on ALI induced by lipopolysaccharide (LPS) through intratracheal instillation. The mRNA and protein expression levels of thioredoxin 1 (Trx1) and the nuclear factor erythroid-2 related factor 2 (Nrf2) were detected by real-time PCR, reverse transcription PCR (RT-PCR) and Western blot, respectively. ROS production was measured by flow cytometry. Our results showed that osthole treatment improved the mice survival rates in the middle and high dosage groups, compared with the untreated LPS group. Moreover, osthole treatment significantly improved LPS-induced lung pathological damage, and it decreased the lung injury scores, lung wet/dry ratios and the total protein level in Bronchoalveolar lavage fluid (BALF). Osthole treatment dramatically reduced the H2O2, MDA and OH levels in the lung homogenates. LDH and ROS were markedly reduced in the osthole+LPS group in vitro. Furthermore, osthole increased Nrf2 and Trx1 expression in terms of mRNA and protein in vivo and in vitro. Nrf2 siRNA (siNrf2) could suppress the beneficial effects of osthole on ALI. In conclusion, the current study demonstrates that osthole exerted protective effects on LPS-induced ALI by up-regulating the Nrf-2/Trx-1 pathway.
authors.affiliation: Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, PR China. goodchenxingjun@163.com
authors.forename: Xiang-Jun
authors.initials: XJ
authors.lastname: Chen
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Shao-Jie
authors.initials: SJ
authors.lastname: Hou
authors.forename: Yun
authors.initials: Y
authors.lastname: Shi
authors.forename: Dun-Quan
authors.initials: DQ
authors.lastname: Xu
authors.forename: Yan-Xia
authors.initials: YX
authors.lastname: Wang
authors.forename: Man-Ling
authors.initials: ML
authors.lastname: Liu
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Dong
authors.forename: Ri-He
authors.initials: RH
authors.lastname: Sun
authors.forename: Nan-Di
authors.initials: ND
authors.lastname: Bao
authors.forename: Fa-Guang
authors.initials: FG
authors.lastname: Jin
authors.forename: Zhi-Chao
authors.initials: ZC
authors.lastname: Li
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D003374:Coumarins / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D002121:Calcium Channel Blockers; D003374:Coumarins; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D013879:Thioredoxins; C046627:osthol
keywords: Acute lung injury; Nrf2; Osthole; Reactive oxygen species; Thioredoxin-1