title: Ethanol extract of the tuber of Alisma orientale reduces the pathologic features in a chronic obstructive pulmonary disease mouse model.
abstract: BACKGROUND
  The tuber of Alismataceae Alisma orientale Juzepzuk has been prescribed as a remedy for treating the diseases associated with body fluid dysfunction such as edema and inflammatory lung diseases. Chronic obstructive pulmonary disease (COPD) is a debilitating, inflammatory lung disease without effective treatment. Along with persistent inflammation, autophagy has been recently reported to contribute to COPD. Here, by employing a murine model, we examined whether the tuber of the plant is effective against COPD MATERIALS AND METHODS: The ethanol extract of the tuber of A. orientale Juzepzuk (EEAO) was fingerprinted by HPLC. For the establishment of COPD lung, mice received single intratracheal (i.t.) spraying of elastase and LPS per week for 2 weeks. After approximated to the dose prescribed typically to patients, EEAO was administered to the lung 2h after each LPS treatment. Morphometric analyses, semi-quantitative RT-PCR, and western blot were performed to evaluate the effects of EEAO on emphysema, inflammation, and autophagy in mouse lungs. The effect of EEAO on autophagy was also assessed by western blot at the cellular level with murine macrophages and human lung epithelial cells.
  
  
  RESULTS
  When receiving i.t. elastase and LPS for 2 weeks, mice developed emphysema and inflammation in the lung. EEAO treatment, however, significantly reduced emphysema and inflammatory cell infiltration to the lung with concomitant decrease of the production of pro-inflammatory cytokines including TNF-α, IL-6, and TGF-β, signature cytokines of COPD. Unlike control mice, the lungs of the COPD mice expressed LC3-II, a biomarker for autophagy formation, which was decreased by EEAO treatment. EEAO also lowered the expression of LC3-II in murine macrophage, RAW 264.7, and human lung epithelial cell, BEAS-2B, which was associated with EEAO activating mTOR.
  
  
  CONCLUSIONS
  EEAO relieved COPD pathologic features in a mouse model, which was associated with suppression of lung inflammation, emphysema, and autophagy. Our results suggest an effectiveness of the tuber of A. orientale in chronic inflammatory lung diseases such as COPD.
authors.affiliation: School of Korean Medicine, Pusan National University, Yangsan 626-870, Republic of Korea.
authors.forename: Kyun Ha
authors.initials: KH
authors.lastname: Kim
authors.affiliation: R&D Team, Agency for Korea National Food Cluster, 460 Iksan-Daero, Iksan, Jeonbuk 507-749, Republic of Korea.
authors.forename: Hyuk-Hwan
authors.initials: HH
authors.lastname: Song
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Chung-Buk 363-883, Republic of Korea.
authors.forename: Kyung-Seop
authors.initials: KS
authors.lastname: Ahn
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Chung-Buk 363-883, Republic of Korea.
authors.forename: Sei-Ryang
authors.initials: SR
authors.lastname: Oh
authors.affiliation: Pulmonary, Critical Care and Sleep Medicine, School of Medicine, Emory University, 1670 Clairmont Rd., Decatur, GA 30033, United States.
authors.forename: Ruxana T
authors.initials: RT
authors.lastname: Sadikot
authors.affiliation: School of Korean Medicine, Pusan National University, Yangsan 626-870, Republic of Korea. Electronic address: mjoo@pusan.ac.kr.
authors.forename: Myungsoo
authors.initials: M
authors.lastname: Joo
mesh_terms: D034902:Alisma / Q000737:chemistry*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000431:Ethanol / Q000737:chemistry*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010196:Pancreatic Elastase; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D035281:Plant Tubers / Q000737:chemistry*; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D029424:Pulmonary Disease, Chronic Obstructive / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000067996:RAW 264.7 Cells; D015398:Signal Transduction / Q000187:drug effects; D012997:Solvents / Q000737:chemistry*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D010936:Plant Extracts; D012997:Solvents; D016212:Transforming Growth Factor beta; D000431:Ethanol; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D010196:Pancreatic Elastase
keywords: Alismataceae Alisma Orientale Juzepzuk; Animal model; Autophagy; Chronic obstructive pulmonary disease; Emphysema; Inflammation