Butein protects human dental pulp cells from hydrogen peroxide-induced oxidative toxicity via Nrf2 pathway-dependent heme oxygenase-1 expressions

• Published in: Toxicology in vitro 2013-03, Vol.27 (2), p.874-881
• Main Authors: Lee, Dong-Sung, Li, Bin, Kim, Kyoung-Su, Jeong, Gil-Saeng, Kim, Eun-Cheol, Kim, Youn-Chul
• Format: Article
• Language: English
• Subjects: Antioxidants - pharmacology; Butein; C-Jun NH2-terminal kinase; Cell Line; Cell Survival - drug effects; Chalcones - pharmacology; Dental Pulp - cytology; Heme oxygenase-1; Heme Oxygenase-1 - metabolism; Human dental pulp cells; Humans; Hydrogen peroxide; Hydrogen Peroxide - toxicity; Mitogen-Activated Protein Kinases - metabolism; NF-E2-Related Factor 2 - metabolism; Nuclear factor-E2-related factor 2; Oxidative Stress - drug effects; Reactive Oxygen Species - metabolism; Rhus
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2013.01.003

► Butein was isolated from Rhus verniciflua Stokes. ► Butein possesses cytoprotective effects on hydrogen peroxide-induced dental cell death. ► Butein increases heme oxygenase-1 protein expression and HO activity. ► Butein showed potent cytoprotective effects via Nrf2/ARE pathway-dependent expression of HO-1. ► Butein may be used to prevent functional dental cell death and useful as a pulpal disease agent. Rhus verniciflua Stokes is a plant that is native to East Asian countries, such as Korea, China, and Japan. Butein, a plant polyphenol, is one of the major active components of R. verniciflua. Reactive oxygen species (ROS), produced via dental adhesive bleaching agents and pulpal disease, can cause oxidative stress. Here, we found that butein possesses cytoprotective effects on hydrogen peroxide (H2O2)-induced dental cell death. H2O2 is a representative ROS and causes cell death through necrosis in human dental pulp (HDP) cells. H2O2-induced cytotoxicity and production of ROS were blocked in the presence of butein, and these effects were dose dependent. Butein also increased heme oxygenase-1 (HO-1) protein expression and HO activity. In addition, butein-dependent HO-1 expression was required for the inhibition of H2O2-induced cell death and ROS generation. Furthermore, butein treatment caused nuclear accumulation of nuclear factor-E2-related factor 2 (Nrf2) and increased the promoter activity of antioxidant response elements (AREs). Treatment of HDP cells with a c-Jun NH2-terminal kinase (JNK) inhibitor also reduced butein-induced HO-1 expression, and butein treatment led to increased JNK phosphorylation. These results indicate that butein may be used to prevent functional dental cell death and thus may be useful as a pulpal disease agent.