Heme oxygenase-1 (HO-1) is an important anti-inflammatory, antioxidative and cytoprotective
enzyme that is regulated by the activation of the major
transcription factor, nuclear factor (erythroid-derived 2)-like 2 (Nrf2). In the present study, six
stilbene derivatives isolated from Rheum undulatum L. were assessed for their antioxidative potential. In the
tert-butylhydroperoxide (t-BHP)-induced RAW 264.7 macrophage cell line,
desoxyrhapontigenin was the most potent component that reduced intracellular
reactive oxygen species (ROS) and
peroxynitrite. In response to
desoxyrhapontigenin, the
mRNA expression levels of
antioxidant enzymes were up-regulated. An electrophoretic mobility shift assay (EMSA) confirmed that
desoxyrhapontigenin promoted the
DNA binding of Nrf2 and increased the expression of
antioxidant proteins and
enzymes regulated by Nrf2. Further investigation utilizing specific inhibitors of Akt, p38, JNK and ERK demonstrated that the
phosphatidylinositol 3-kinase (PI3K)/Akt pathway mediates HO-1 expression. Moreover, the increase in Nrf2 expression mediated by treatment with
desoxyrhapontigenin was reversed by Nrf2 or Akt gene knock-down. In the LPS-induced in vivo
lung inflammation model, pretreatment with
desoxyrhapontigenin markedly ameliorated LPS-induced
lung inflammation and histological changes. Immunohistochemical analysis of Nrf2, HO-1 and p65 was conducted and confirmed that treatment with
desoxyrhapontigenin induced Nrf2 and HO-1 expression but reduced p65 expression. These findings suggest that
desoxyrhapontigenin may be a potential therapeutic candidate as an
antioxidant or an
anti-inflammatory agent.