title: Protective effects of pogostone against LPS-induced acute lung injury in mice via regulation of Keap1-Nrf2/NF-κB signaling pathways.
abstract: Pogostone, a major component of Pogostemon cablin, has been demonstrated to possess antibacterial, anti-fungal, immunosuppressive and anti-inflammatory properties. To investigate the potential therapeutic effect of pogostone on lipopolysaccharide (LPS)-induced acute lung injury (ALI), mice were pretreated with pogostone prior to LPS exposure. After LPS challenge, the lungs were excised and the histological changes, wet to dry weight ratios, MPO activity reflecting neutrophil infiltration, and MDA activity reflecting oxidative stress were examined. The inflammatory cytokines in the BALF were determined by ELISA assay. Moreover, the expressions of p65 and phosphorylated p65 subunit of NF-κB, and Nrf2 in the nucleus in lung tissues were measured by Western blot analysis, and meanwhile the dependent genes of NF-κB and Nrf2 were assessed by RT-qPCR. The results showed that pretreatment with pogostone markedly improved survival rate, attenuated the histological alterations in the lung, reduced the MPO and MDA levels, decreased the wet/dry weight ratio of lungs, down-regulated the level of pro-inflammatory mediators including TNF-a, IL-1β and IL-6. Furthermore, pretreatment with pogostone enhanced the Nrf2 dependent genes including NQO-1, GCLC and HO-1 but suppressed NF-κB regulated genes including TNF-α, IL-1β and IL-6. The mechanism behind the protective effect was correlated with its regulation on the balance between Keap1-Nrf2 and NF-κB signaling pathways. Therefore, pogostone may be considered as a potential therapeutic agent for preventing and treating ALI.
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, no. 232, Waihuandong Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, PR China.
authors.forename: Chao-Yue
authors.initials: CY
authors.lastname: Sun
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, no. 232, Waihuandong Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, PR China.
authors.forename: Lie-Qiang
authors.initials: LQ
authors.lastname: Xu
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, no. 232, Waihuandong Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, PR China.
authors.forename: Zhen-Biao
authors.initials: ZB
authors.lastname: Zhang
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, no. 232, Waihuandong Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, PR China.
authors.forename: Chao-Hui
authors.initials: CH
authors.lastname: Chen
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, no. 232, Waihuandong Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, PR China.
authors.forename: Yong-Zhong
authors.initials: YZ
authors.lastname: Huang
authors.affiliation: Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, Guangdong, PR China.
authors.forename: Zu-Qing
authors.initials: ZQ
authors.lastname: Su
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, PR China.
authors.forename: Hui-Zhen
authors.initials: HZ
authors.lastname: Guo
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, no. 232, Waihuandong Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, PR China.
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Chen
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, no. 232, Waihuandong Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, PR China.
authors.forename: Xie
authors.initials: X
authors.lastname: Zhang
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, no. 232, Waihuandong Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, PR China.
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Liu
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, no. 232, Waihuandong Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, PR China.
authors.forename: Jian-Nan
authors.initials: JN
authors.lastname: Chen
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, no. 232, Waihuandong Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, PR China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Lai
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, no. 232, Waihuandong Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, PR China. Electronic address: liyucui@gzucm.edu.cn.
authors.forename: Yu-Cui
authors.initials: YC
authors.lastname: Li
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, no. 232, Waihuandong Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, PR China; Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Songshan Lake High-tech Industrial Development Zone, Dongguan 523808, Guangdong, PR China. Electronic address: suziren@gzucm.edu.cn.
authors.forename: Zi-Ren
authors.initials: ZR
authors.lastname: Su
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003598:Cytoskeletal Proteins / Q000276:immunology; D000072019:Kelch-Like ECH-Associated Protein 1; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology; D009822:Oils, Volatile / Q000494:pharmacology* / Q000627:therapeutic use*; D009195:Peroxidase / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D003598:Cytoskeletal Proteins; C117301:Keap1 protein, mouse; D000072019:Kelch-Like ECH-Associated Protein 1; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495636:Nfe2l2 protein, mouse; D009822:Oils, Volatile; C483658:Pogostone; D008315:Malondialdehyde; D009195:Peroxidase
keywords: Acute lung injury (ALI); Lipopolysaccharide (LPS); NF-κB; Nrf2; Pogostone (PO)