PMID- 26293030 OWN - NLM STAT- MEDLINE DCOM- 20160401 LR - 20191210 IS - 1873-2623 (Electronic) IS - 0041-1345 (Linking) VI - 47 IP - 6 DP - 2015 Jul-Aug TI - Carnosol Is a Potent Lung Protective Agent: Experimental Study on Mice. PG - 1657-61 LID - S0041-1345(15)00518-7 [pii] LID - 10.1016/j.transproceed.2015.05.004 [doi] AB - INTRODUCTION: 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 degrees 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. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Kawamura, T AU - Kawamura T AD - 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. FAU - Momozane, T AU - Momozane T AD - Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan; Laboratory of Cell Signaling & Metabolic Disease. FAU - Sanosaka, M AU - Sanosaka M AD - Laboratory of Cell Signaling & Metabolic Disease. FAU - Sugimura, K AU - Sugimura K AD - Research Center for Medicinal Plant Resources, National Institute of Biomedical Innovation, Osaka, Japan. FAU - Iida, O AU - Iida O AD - Research Center for Medicinal Plant Resources, National Institute of Biomedical Innovation, Osaka, Japan. FAU - Fuchino, H AU - Fuchino H AD - Research Center for Medicinal Plant Resources, National Institute of Biomedical Innovation, Osaka, Japan. FAU - Funaki, S AU - Funaki S AD - Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan. FAU - Shintani, Y AU - Shintani Y AD - Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan. FAU - Inoue, M AU - Inoue M AD - Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan. FAU - Minami, M AU - Minami M AD - Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan. FAU - Kawahara, N AU - Kawahara N AD - Research Center for Medicinal Plant Resources, National Institute of Biomedical Innovation, Osaka, Japan. FAU - Takemori, H AU - Takemori H AD - Laboratory of Cell Signaling & Metabolic Disease. FAU - Okumura, M AU - Okumura M AD - Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Transplant Proc JT - Transplantation proceedings JID - 0243532 RN - 0 (Abietanes) RN - 0 (Antioxidants) RN - 0 (NF-E2-Related Factor 2) RN - 0 (Plant Extracts) RN - 483O455CKD (carnosol) RN - EC 1.1.- (Lactate Dehydrogenases) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - LI791SXT24 (salvin) SB - IM MH - Abietanes/*pharmacology MH - Animals MH - Antioxidants/*pharmacology MH - Heme Oxygenase-1/metabolism MH - Lactate Dehydrogenases/metabolism MH - Lung/*drug effects/metabolism/pathology MH - Lung Injury/metabolism/pathology MH - Lung Transplantation/adverse effects MH - Male MH - Mice MH - NF-E2-Related Factor 2/metabolism MH - Oxidation-Reduction MH - Oxidative Stress/*drug effects MH - Plant Extracts/*pharmacology MH - Reperfusion Injury/metabolism/pathology EDAT- 2015/08/22 06:00 MHDA- 2016/04/02 06:00 CRDT- 2015/08/22 06:00 PHST- 2015/02/15 00:00 [received] PHST- 2015/05/11 00:00 [revised] PHST- 2015/05/14 00:00 [accepted] PHST- 2015/08/22 06:00 [entrez] PHST- 2015/08/22 06:00 [pubmed] PHST- 2016/04/02 06:00 [medline] AID - S0041-1345(15)00518-7 [pii] AID - 10.1016/j.transproceed.2015.05.004 [doi] PST - ppublish SO - Transplant Proc. 2015 Jul-Aug;47(6):1657-61. doi: 10.1016/j.transproceed.2015.05.004.