Isoorientin induces Nrf2 pathway-driven antioxidant response through phosphatidylinositol 3-kinase signaling.
Because oxidative stress is involved in the pathogenesis of various chronic diseases and the aging process, antioxidants that can increase the intrinsic antioxidant potency are proposed as desirable therapeutic agents to counteract oxidative stress-related diseases. NF-E2-related factor-2 (Nrf2) is a transcription factor that regulates important antioxidant and phase II detoxification genes, and therefore, the molecule that regulates nuclear translocation of Nrf2 and the induction of antioxidative proteins is thought to be a promising candidate as a cytoprotective agent for oxidative stress. In the present study, we show that isoorientin (luteolin 6-C-beta-D-glucoside) obtained from the leaves of Sasa borealis upregulates and activates Nrf2, and has protective ability against oxidative damage caused by reactive oxygen intermediates in HepG2 cells. Isoorientin induces increase in the level of antioxidant enzyme proteins, especially NQO1, and the cytoprotective and antioxidative effects of isoorientin are PI3K/Akt pathway-dependent. Together with direct radical scavenging activity, the novel effect of isoorientin on the regulation of antioxidative gene expression provides attractive strategy to prevent diseases associated with oxidative stress and attenuate the progress of the diseases.
Lim
Ju Hee
JH
College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, Korea.
Park
Hae-Suk
HS
Choi
Jung-Kap
JK
Lee
Ik-Soo
IS
Choi
Hyun Jin
HJ
D021581:Active Transport, Cell Nucleus; D000975:Antioxidants / Q000378:metabolism*; D002478:Cells, Cultured; D019610:Cytoprotection; D006801:Humans; D047311:Luteolin / Q000494:pharmacology*; D051267:NF-E2-Related Factor 2 / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D015398:Signal Transduction; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D020122:tert-Butylhydroperoxide; C057912:homoorientin; D019869:Phosphatidylinositol 3-Kinases; D047311:Luteolin