Study on Activation of Nuclear Factor Erythroid 2-related Factor 2 Pathway with Fructus Schisandrae Extracts Medicated by Kinase Pathways Such as Extracellular Signal-regulated Kinase / 广州中医药大学学报

ABSTRACT

Objective To observe the influence of several kinase pathways such as extracellular signal-regulated kinase ( ERK) , and mitogen-activated protein kinase p38 ( p38MAPK) on nuclear factor erythroid 2-related factor 2 (Nrf2) pathway activated by Fructus Schisandrae extracts (FSE) . Methods HepG2 cells were treated by FSE for 24 hours after pretreatment with protein kinase inhibitors for 2 hours. The mRNA expression levels of Nrf2 and downstream target genes heme oxygenase-1 (HO-1), NAD (P) H quinine oxidoreductase 1(NQO1), P-glycoprotein ( P-gp) and multidrug resistance-associated protein 2 ( MRP2) were detected by real-time polymerase chain reaction ( RT-PCR) , and their protein expression levels and Nrf2 nuclear translocation were measured by Western blotting method. Results RT-PCR results showed that the mRNA expression levels of HO-1, NQO1, P-gp and MRP2 activated by FSE in HepG2 cells were inhibited by PD98059, SB203580 and Rottlerin, and the mRNA expression of Nrf2 was suppressed only by SB203580 and Rottlerin. Western blotting results showed that the mRNA expression levels of HO-1 and P-gp activated by SCE in HepG2 cells were inhibited by PD98059, SB203580 and Rottlerin. In addition, the protein expression of Nrf2 in HepG2 cytoplasm was increased by the above three inhibitors, and nuclear translocation of Nrf2 was inhibited by PD98059 and SB203580. Conclusion The mechanism of FSE activating Nrf2 pathway may be associated with the increase of Nrf2 nuclear translocation through the direct phosphorylation of Nrf2 induced by ERK and p38MAPK.