title: Osthole protects lipopolysaccharide-induced acute lung injury in mice by preventing down-regulation of angiotensin-converting enzyme 2.
abstract: The renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Angiotensin converting enzyme 2 (ACE2) plays a protective role in acute lung injury. Osthole, a natural coumarin derivative extracted from traditional Chinese medicines, is known to have anti-inflammatory effect, but the effect of osthole on the ALI is largely unknown. The aim of this study is to explore whether and by what mechanisms osthole protects lipopolysaccharide(LPS)-induced acute lung injury. Herein, we found that osthole had a beneficial effect on LPS-induced ALI in mice. As revealed by survival study, pretreatment with high doses of osthole reduced the mortality of mice from ALI. Osthole pretreatment significantly improved LPS-induced lung pathological changes, reduced lung wet/dry weight ratios and total protein in BALF. Osthole also inhibited the release of inflammatory mediators TNF-α and IL-6. Meanwhile, osthole markedly prevented the loss of ACE2 and Ang1-7 in lung tissue of ALI mice. ACE2 inhibitor blocked the protective effect of osthole in NR 8383 cell lines. Taken together, our study showed that osthole improved survival rate and attenuated LPS-induced ALI and ACE2 may play a role in it.
authors: Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, PR China. shiyunde@126.com
authors: Yun
authors: Y
authors: Shi
authors: Bo
authors: B
authors: Zhang
authors: Xiang-Jun
authors: XJ
authors: Chen
authors: Dun-Quan
authors: DQ
authors: Xu
authors: Yan-Xia
authors: YX
authors: Wang
authors: Hai-Ying
authors: HY
authors: Dong
authors: Shi-Rong
authors: SR
authors: Ma
authors: Ri-He
authors: RH
authors: Sun
authors: Yan-Ping
authors: YP
authors: Hui
authors: Zhi-Chao
authors: ZC
authors: Li
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000803:Angiotensin I / Q000378:metabolism; D000085962:Angiotensin-Converting Enzyme 2; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002460:Cell Line; D003374:Coumarins / Q000494:pharmacology / Q000627:therapeutic use*; D015536:Down-Regulation / Q000187:drug effects; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000893:Anti-Inflammatory Agents; D003374:Coumarins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705328:Ace2 protein, mouse; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7); C046627:osthol