title: Icaritin attenuates cigarette smoke-mediated oxidative stress in human lung epithelial cells via activation of PI3K-AKT and Nrf2 signaling.
abstract: Icariin is the major active ingredient of Herba Epimedii. Icaritin (ICT) is a hydrolytic product of Icariin. In the present study, we investigated the protective role of ICT against cigarette smoke extract (CSE)-mediated oxidative stress in human lung epithelial A549 cells. As demonstrated by the WST-8 assay, exposure to CSE (2.5%, 5%, and 10%) reduced the cell viability of A549 cells (84%, 64% and 53%) in a dose-dependent manner and treatment with ICT 10 μM dramatically attenuated CSE induced cytotoxicity (73% and 64%). The MFI data suggested that CSE induced oxidative stress by generating ROS (230) and 10 μM ICT treatment attenuated CSE-induced ROS production (90). 10 μM ICT treatment resulted in significant AKT activation, Nrf2 nuclear translocation, increased GCL transcription and GSH levels, as compared with CSE exposure alone. However, ICT-mediated upregulation of GCL transcription in CSE-treated cells were lost in Nrf2 siRNA-transfected cells. Furthermore, inhibition of PI3K/AKT signaling by LY294002 partially prevents ICT-induced nuclear translocation of Nrf2 and GCL transcription. These findings suggest that ICT attenuates CS-induced oxidative stress by quenching ROS and also by upregulating GSH via a PI3K-AKT-Nrf2-dependent mechanism. Further studies are required to confirm that a similar protective effect of ICT occurs in the lungs in vivo in response to CS exposure.
authors: Department of Integrative Medicine, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai 200040, China; Department of Dermatology, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai 200040, China.
authors: Jinfeng
authors: J
authors: Wu
authors: Department of Integrative Medicine, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai 200040, China.
authors: Hailin
authors: H
authors: Xu
authors: Edward Ford Building A27, Sydney Medical School, The University of Sydney, New South Wales 2006, Australia.
authors: Pok Fai
authors: PF
authors: Wong
authors: Shanghai Geriatrics Institute, Huadong Hospital, Fudan University, 221 West Yanan Road, Shanghai 200040, China.
authors: Shijin
authors: S
authors: Xia
authors: Department of Dermatology, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai 200040, China. Electronic address: jhxu2012@gmail.com.
authors: Jinhua
authors: J
authors: Xu
authors: Department of Integrative Medicine, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai 200040, China. Electronic address: jcdong2004@126.com.
authors: Jingcheng
authors: J
authors: Dong
mesh_terms: D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D005434:Flow Cytometry; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D012906:Smoke / Q000009:adverse effects*; D014158:Transcription, Genetic
chemical_list: D002867:Chromones; D005419:Flavonoids; C549075:LY 290042; D009025:Morpholines; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D017382:Reactive Oxygen Species; D012906:Smoke; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D005978:Glutathione; C499403:icaritin
keywords: Cigarette smoke; Icaritin; Lung epithelial cells; Nrf2; Oxidative stress; PI3K-AKT