Antioxidative Effects of Cherry Leaves Extract on tert-Butyl Hydroperoxide-Mediated Cytotoxicity Through Regulation of Thioredoxin-2 Protein Expression Levels

Abstract

Components of cherry trees have been used as traditional herbal remedies for various diseases. These components are known to possess antioxidative effects. However, the mechanisms underlying cherry tree component-mediated antioxidative effects remain largely unknown. This study focused on cherry leaves extract (CLE) and examined the mechanism underlying the effect of CLE on tert-butyl hydroperoxide (t-BOOH)-induced melanocytic cell death with DNA damage. Interestingly, CLE prevented t-BOOH-induced cell death with reduction in DNA damage, p38 kinase activation, and reactive oxygen species (ROS) production. CLE-mediated suppression of cell death with reduction of DNA damage, p38 kinase activity and ROS production was prevented by a thioredoxin (Trx) system inhibitor but not by a glutathione (GSH) system inhibitor. Finally, data showed that CLE prevented t-BOOH-induced reduction of Trx2 but not Trx1 and Trx reductases (TrxR1 and TrxR2) protein expression. Thus, our results suggest that CLE prevents t-BOOH-induced reduction in Trx2 expression, promotion of ROS production, activation of p38 kinase, and increase in DNA damage and that it protects against cell death.

Acknowledgments

This study was supported in part by Grants-in-Aid for Scientific Research (B) (19390168 and 20406003) and COE Project for Private Universities (S0801055) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), JSPS AA Science Platform Program, Mitsui & Co., Ltd. Environment Fund (R08-C097), Lydia O'Leary Memorial Foundation, and Aichi Science & Technology Foundation.

Notes

The first two authors made equal contributions to this work.