Maslinic acid induces HO-1 and NOQ1 expression via activation of Nrf2 transcription factor

Abstract Maslinic acid, a naturally-occurring pentacyclic triterpene, has been shown to suppress pro-inflammatory enzyme COX-2 expression and inhibit redox sensitive transcription factors NF-κB and AP-1 binding activities. In this study, the effects of maslinic acid at inducing cytoprotective enzymes via the Nrf2-ARE pathway in HepG2 cells were investigated. Results showed that maslinic acid significantly induced HO-1 and NQO1 expression in a concentration-dependent manner and achieves maximal expression at 100 μM after six hours of treatment. The up-regulation of HO-1 and NQO1 expression might be resulted from maslinic acid-induced ARE binding activity observed from three to 12 h. Maslinic acid also enhanced nuclear Nrf2 protein accumulation up to 172% after three hours of treatment. These results suggest that maslinic acid may induce nuclear Nrf2 accumulation, binding to the ARE and transcriptionally activate HO-1 and NQO1 expression. In addition, maslinic acid significantly induced HO-1 and NQO1 expression in Con-siRNA-transfected cells but this effect was abrogated in cells transfected with Nrf2-siRNA. In conclusion, maslinic acid induces HO-1 and NQO1 enzyme expressions and the transcription factor Nrf2 is essential for the induction of these enzymes.