Abstracto

Phyllanthus emblica L. extract activates Nrf2 signalling pathway in HepG2 cells

Fei Wang, Hongying Wang

To investigate the effects of Extracellular signal-Regulated Kinase (ERK), p38 mitogen-Activated Protein Kinase (p38MAPK) and other kinase pathways on the activation of Nuclear related factor 2 (Nrf2) signalling pathway by Phyllanthus emblica L. extract (PET). After pre-treatment with different protease inhibitors for 2 h, cells were interfered with Phyllanthus emblica L. extract for 24 h. mRNA expressions of Nrf2 and downstream target genes HO-1, NQO1, P-gp, MRP2 were detected by RT-PCR. Protein level and nuclear translocation of Nrf2 were detected by Western blotting. RT-PCR results showed that treatment with PD98059, SB203580 and rottlerin suppressed the HO-1, NQO1, P-gp and MRP2 mRNA induction by PET, but only treatment with SB203580 and rottlerin could inhibit the Nrf2 mRNA expression by the extract. Western blotting showed that treatment with PD98059, SB203580 and rottlerin suppressed the HO-1 and P-gp protein inducing effect of PET. Treatment with various inhibitors could all induce the cytoplasmic expression of Nrf2 protein, but treatment with PD98059 and SB203580 could inhibit nuclear translocation of Nrf2. Nrf2 pathway activating mechanisms of PET may be associated with the roles of ERK and p38MAPK in directly phosphorylating Nrf2 and promoting Nrf2 nuclear import to increase its nuclear accumulation.