title: Hepatoprotection of quercetin against oxidative stress by induction of metallothionein expression through activating MAPK and PI3K pathways and enhancing Nrf2 DNA-binding activity.
abstract: Flavonoids are natural phenolic substances widely found in fruit, vegetables, grains, and wine. Most of these compounds exert health-promoting effects seem to attribute to their antioxidant activity. Metallothioneins (MT) has been suggested to protect against acute heavy metal toxicity in the liver, and the proteins of MT can be induced by various stimuli including antioxidant. Measuring the induction of MT genes may provide an efficient approach to understand the chemopreventive mechanisms of flavonoids. The antioxidant activity of eight flavonoids was determined by TEAC and ORAC assays and their effects on MT protein were also measured. HepG2 cells were employed to explore the mechanisms underlying flavonoid-induced MT induction. Statistical analysis revealed a positive correlation between the antioxidant activity of flavonoids and MT expression. Quercetin-induced MT expression may function by activating the phosphorylation of JNK, p38 and PI3K/Akt as well as by enhancing Nrf2 DNA-binding activity. Moreover, quercetin exhibited a potential protective effect on t-BHP-caused injury in hepatocytes through the induction of MT. These results suggest that quercetin is a natural antioxidant in the diet and the consumption of foods that are rich in quercetin could be beneficial for the prevention of environmental oxidant-induced liver damage.
authors.affiliation: Graduate Institute of Applied Science of Living, Tainan University of Technology, 529 Zhongzheng Rd., Yongkang District, Tainan City 71002, Taiwan.
authors.forename: Chia-Jui
authors.initials: CJ
authors.lastname: Weng
authors.forename: Mei-Jung
authors.initials: MJ
authors.lastname: Chen
authors.forename: Chi-Tai
authors.initials: CT
authors.lastname: Yeh
authors.forename: Gow-Chin
authors.initials: GC
authors.lastname: Yen
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D056945:Hep G2 Cells; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D008668:Metallothionein / Q000096:biosynthesis*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D008668:Metallothionein; D011794:Quercetin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4