Emerging Perspectives in TransplantationIschemia reperfusion injuryCarnosol Is a Potent Lung Protective Agent: Experimental Study on Mice

•Callicarpa longissima extract was rich in NRF2 activators.•The responsible compounds were carnosic acid and its oxidative product, carnosol.•Carnosol is a candidate compound to increase the success rate of lung transplantation.

IntroductionOxidative 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.MethodsWe 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.ResultsWe 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.ConclusionsLungs 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.