Isoforskolin pretreatment attenuates lipopolysaccharide-induced acute lung injury in animal models
Yang, Weimin1; Qiang, Dongjin1; Zhang, Min1; Ma, Limei1; Zhang, Yonghui1; Qing, Chen1; Xu, Yunlong2; Zhen, Chunlan1; Liu, Jikai2; Chen, Yan-Hua3
Corresponding AuthorYang, WM (reprint author), Kunming Med Coll, Yunnan Key Lab Pharmacol Nat Prod, Kunming 650031, Peoples R China
2011-06-01
Source PublicationINTERNATIONAL IMMUNOPHARMACOLOGY
ISSN1567-5769
Volume11Issue:6Pages:683-692
AbstractIsoforskolin was isolated from Coleus forskohlii native to Yunnan in China. We hypothesize that isuforskolin pretreatment attenuates acute lung injury induced by lipopolysaccharide (endotoxin). Three acute lung injury models were used: situ perfused rat lung, rat and mouse models of endotoxic shock. Additionally, lipopolysaccharide stimulated proinflammatory cytokine production was evaluated in human mononuclear leukocyte. In situ perfused rat lungs, pre-perfusion with isoforskolin (100, and 200 mu M) and dexarrethasone (65 mu M, positive control) inhibited lipopolysaccharide (10 mg/L) induced increases in lung neutrophil adhesion rate, myeloperoxidase activity, lung weight Wet/Dry ratio, permeability-surface area product value, and tumor necrosis factor (TNF)-alpha levels. In rats, pretreatments with isoforskolin (5, 10, and 20 mg/kg, i.p.) and dexamethasone (5 mg/kg, i.p.) markedly reduced lipopolysaccharide (6 mg/kg i.v.) induced increases of karyocyte, neutrophil counts and protein content in bronchoalveolar lavage fluid, and plasma myeloperoxidase activity. Lung histopathology showed that morphologic changes induced by lipopolysaccharide were less pronounced in the isoforskolin and dexamethasone pretreated rats. In mice, 5 mg/kg isoforskolin and dexamethasone caused 100% and 80% survival, respectively, after administration of lipopolysaccharide (62.5 mg/kg, iv., 40% survival if untreated). In human mononuclear leukocyte, isoforskolin (50, 100, and 200 mu M) and dexamethasone (10 mu M) pre-incubation lowered lipopolysaccharide (2 mu g/mL) induced secretion of the cytokine TNF-alpha, and interleukins (IL)-1 beta, IL-6, and IL-8. In conclusion, pretreatment with isoforskolin attenuates lipopolysaccharide-induced acute lung injury in several models, and it is involved in down-regulation of inflammatory responses and proinflammatory cytokines TNF-alpha, IL-1 beta, IL-6, and IL-8. (C) 2011 Elsevier B.V. All rights reserved.
KeywordAcute Lung Injury Isoforskolin Lipopolysaccharide Inflammation Cytokine
Subject AreaImmunology ; Pharmacology & Pharmacy
DOI10.1016/j.intimp.2011.01.011
Indexed BySCI
Language英语
WOS IDWOS:000291505900007
Citation statistics
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/5353
Collection植物化学与西部植物资源持续利用国家重点实验室
Affiliation1.Kunming Med Coll, Yunnan Key Lab Pharmacol Nat Prod, Kunming 650031, Peoples R China
2.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources W China, Kunming 650204, Peoples R China
3.E Carolina Univ, Brody Sch Med, Dept Anat & Cell Biol, Greenville, NC 27834 USA
Recommended Citation
GB/T 7714
Yang, Weimin,Qiang, Dongjin,Zhang, Min,et al. Isoforskolin pretreatment attenuates lipopolysaccharide-induced acute lung injury in animal models[J]. INTERNATIONAL IMMUNOPHARMACOLOGY,2011,11(6):683-692.
APA Yang, Weimin.,Qiang, Dongjin.,Zhang, Min.,Ma, Limei.,Zhang, Yonghui.,...&Chen, Yan-Hua.(2011).Isoforskolin pretreatment attenuates lipopolysaccharide-induced acute lung injury in animal models.INTERNATIONAL IMMUNOPHARMACOLOGY,11(6),683-692.
MLA Yang, Weimin,et al."Isoforskolin pretreatment attenuates lipopolysaccharide-induced acute lung injury in animal models".INTERNATIONAL IMMUNOPHARMACOLOGY 11.6(2011):683-692.
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