title: Carnosol Is a Potent Lung Protective Agent: Experimental Study on Mice.
abstract: BACKGROUND
  Oxidative stress has been implicated in various disease states and ischemia/reperfusion injury is a direct consequence of oxidative stress in lung transplantation. Because the success rate of organ transplantation in which ischemia/reperfusion is inevitable is highly influenced by oxidative stress, development of strategies to control oxidative stress would be beneficial. Here we identified natural compounds to reduce oxidative stresses in isolated mouse lungs.
  
  
  METHODS
  We screened compounds associated with antioxidative stress in 200 plant extracts by monitoring the activities of nuclear factor erythroid 2-related factor 2 (NRF2). Compounds found to ameliorate antioxidative stress were enriched and mice were administered the extract orally every day for 1 week. Then, the lungs were isolated and cultured in the culture medium at 37 °C. Lung damage was monitored by lactate dehydrogenase (LDH) released in the culture medium. Arterial (left ventricle) blood gas levels were also monitored after hilar clamping.
  
  
  RESULTS
  We found that Callicarpa longissima extract was rich in NRF2 activators. The responsible compounds were carnosic acid and its oxidative product, carnosol. Carnosol induced heme-oxygenase 1 (HO-1) expression, which is downstream of NRF2, more efficiently than carnosic acid.
  
  
  CONCLUSIONS
  Lungs from mice treated with C longissima extract were less damaged than those from control mice and accompanied by HO-1 induction. These results suggest that carnosol is a candidate compound to increase the success rate of lung transplantation.
authors: Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan; Laboratory of Cell Signaling & Metabolic Disease. Electronic address: tkawamu@thoracic.med.osaka-u.ac.jp.
authors: T
authors: T
authors: Kawamura
authors: Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan; Laboratory of Cell Signaling & Metabolic Disease.
authors: T
authors: T
authors: Momozane
authors: Laboratory of Cell Signaling & Metabolic Disease.
authors: M
authors: M
authors: Sanosaka
authors: Research Center for Medicinal Plant Resources, National Institute of Biomedical Innovation, Osaka, Japan.
authors: K
authors: K
authors: Sugimura
authors: Research Center for Medicinal Plant Resources, National Institute of Biomedical Innovation, Osaka, Japan.
authors: O
authors: O
authors: Iida
authors: Research Center for Medicinal Plant Resources, National Institute of Biomedical Innovation, Osaka, Japan.
authors: H
authors: H
authors: Fuchino
authors: Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors: S
authors: S
authors: Funaki
authors: Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors: Y
authors: Y
authors: Shintani
authors: Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors: M
authors: M
authors: Inoue
authors: Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors: M
authors: M
authors: Minami
authors: Research Center for Medicinal Plant Resources, National Institute of Biomedical Innovation, Osaka, Japan.
authors: N
authors: N
authors: Kawahara
authors: Laboratory of Cell Signaling & Metabolic Disease.
authors: H
authors: H
authors: Takemori
authors: Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors: M
authors: M
authors: Okumura
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D045022:Lactate Dehydrogenases / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000378:metabolism / Q000473:pathology; D016040:Lung Transplantation / Q000009:adverse effects; D008297:Male; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology
chemical_list: D045784:Abietanes; D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D010936:Plant Extracts; C068623:carnosol; D045022:Lactate Dehydrogenases; D051547:Heme Oxygenase-1; C018381:salvin