title: The protective effect of Trillin LPS-induced acute lung injury by the regulations of inflammation and oxidative state.
abstract: Inflammation response and oxidative stress have been reported to be involved in the pathogenesis of acute lung injury (ALI). Accordingly, anti-inflammatory treatment is proposed to be a possible efficient therapeutic strategy for ALI. The purpose of our present study was to evaluate the anti-inflammatory efficacy of trillin (Tr) on ALI induced by lipopolysaccharide (LPS) in mice and explore the underlying mechanism. BALB/c mice received Tr (50, 100 mg/kg) intraperitoneally 1 h prior to the intratracheal instillation of lipopolysaccharide (LPS) challenge. Pretreatment with Tr at the dose of 50, 100 mg/kg markedly ameliorated lung wet-to-dry weight (W/D) ratio, myeloperoxidase (MPO) activity and pulmonary histopathological conditions. In addition, the protective efficacy of Tr might be attributed to the down-regulations of neutrophil infiltration, malondialdehyde (MDA), inflammatory cytokines and the up-regulations of super-oxide dismutase (SOD), catalase(CAT), glutathione(GSH), Glutathione Peroxidase(GSH-Px) in bronchoalveolar lavage fluid (BALF). Meanwhile, our study revealed some correlations between (NF-E2-related factor 2) Nrf2/heme oxygenase (HO)-1/nuclear factor-kappa B (NF-κB) pathways and the beneficial effect of Tr, as evidenced by the significant up-regulations of HO-1 and Nrf2 protein expressions as well as the down-regulations of p-NF-κB and p-inhibitor of NF-κB (IκB) in lung tissues. Taken together, our results indicated that Tr exhibited protective effect on LPS-induced ALI by the regulations of related inflammatory events via the activations of Nrf2, HO-1 and NF-κB pathway. The current study indicated that Tr could be a potentially effective candidate medicine for the treatment of ALI.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Wenjiao
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Physiology and Pharmacology, China Pharmaceutical University, Tongjiaxiang 24, Nanjing, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Qianfeng
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Department of Physiology and Pharmacology, China Pharmaceutical University, Tongjiaxiang 24, Nanjing, China.
authors.forename: Jingyan
authors.initials: J
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Peijin
authors.initials: P
authors.lastname: Li
authors.affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Wang
authors.affiliation: The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu 322000, China.
authors.forename: Yeliu
authors.initials: Y
authors.lastname: Fu
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Hao
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Department of Physiology and Pharmacology, China Pharmaceutical University, Tongjiaxiang 24, Nanjing, China. Electronic address: Yantianhuabest@126.com.
authors.forename: Tianhua
authors.initials: T
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Department of Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China. Electronic address: dxs0162@sina.com.
authors.forename: Xuansheng
authors.initials: X
authors.lastname: Ding
mesh_terms: D055371:Acute Lung Injury / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000627:therapeutic use*; D000975:Antioxidants / Q000737:chemistry / Q000627:therapeutic use*; D016207:Cytokines / Q000276:immunology; D027743:Dioscoreaceae / Q000737:chemistry; D051547:Heme Oxygenase-1 / Q000276:immunology; D007249:Inflammation / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008070:Lipopolysaccharides / Q000276:immunology; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D051267:NF-E2-Related Factor 2 / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry; D012503:Saponins / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016207:Cytokines; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D010936:Plant Extracts; D012503:Saponins; D051547:Heme Oxygenase-1
keywords: Acute lung injury; HO-1; NF-κB; Nrf2; Trillin