Hawthorn (Crataegus oxyacantha L.) Bark Extract Regulates Antioxidant Response Element (ARE)‐Mediated Enzyme Expression Via Nrf2 Pathway Activation in Normal Hepatocyte Cell Line
2014
Krajka‐Kuźniak, Violetta | Paluszczak, Jarosław | Oszmiański, Jan | Baer‐Dubowska, Wanda
Hawthorn (Crataegus oxyacantha L.), a plant used in traditional medicine, is a rich source of procyanidins which have been reported to exhibit antioxidant and anti‐carcinogenic activity. In this study, we assessed the effect of hawthorn bark extract (HBE) on Nrf2 pathway activation in THLE‐2 and HepG2 cells. Treatment with 1.1 µg/mL, 5.5 µg/mL and 11 µg/mL of HBE resulted in the translocation of Nrf2 from the cytosol to the nucleus in both cell lines; however, the accumulation of phosphorylated Nrf2 was observed only in THLE‐2. Accordingly, treatment of cells with HBE was associated with an increase in the mRNA and protein level of such Nrf2‐dependent genes as glutathione S‐transferases (GSTA, GSTP, GSTM, GSTT), NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase‐1 (HO‐1) (0.2–1.1‐fold change, p < 0.05), however, only in normal THLE‐2 hepatocytes. The induction of NQO1 correlated with an increased level of p53 (0.21–0.42‐fold change, p < 0.05). These effects may be related to induction of phosphorylation of upstream ERK and JNK kinases. Collectively, the results suggest that the Nrf2/ARE pathway may play an important role in the regulation of procyanidin‐mediated antioxidant/detoxifying effects in hepatocytes, and this may explain the hepatoprotective and chemopreventive properties of these phytochemicals.
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