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

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.