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Oxidative-stress induce a large number of physiological and pathological responses in cells and tissues, so directly or indirectly, through a variety of ways to effectively inhibit, block, remove or repair a variety of oxidative damage, is expected to become a new strategy for the treatment of a series of diseases.However, with an increasing number of toxic side effects was exposed in the synthetic antioxidants (such as tBHQ), which has been gradually banned, the idea of "return to nature" has become the mainstream of the world, it has become the focus of domestic and foreign to explore a new natural antioxidants. Magnoliae officinalis is a resourceful and widely distributed in China’s north-south around over ten provinces as a traditional Chinese medical herb. Magnolol and Honokiol are important functional compositions in Magnoliae officinalis.As the main natural active ingredients of Magnolia officinalis which is traditional Chinese medicine, Magnolol (MG) and Honokiol (HK) showed very significant anti-oxidation, anti-aging, anti-inflammatory, anti-bacterial, anti-tumor and other biological activity, and have a wide range of resources, thus they cause extensive attention from researchers. But MG and HK pharmacology studies focused on inflammation, cancer and other pathological model, it is not very clear that the cellular and molecular mechanisms and network of signal transduction pathway of the antioxidant activity in normal cells.Therefore, this study has established the H2O2oxidative stress model of L02cells, and using western blotting detect the Nrf2, Nf-KB and its upstream signaling pathways MAPKs to explore the dose-effect relationship and regulation mechanism of anti-oxidation physiological activity of the MG and HK, which a natural polyphenolic compounds.1The cell viability of normal L02cells was significantly enhanced by MG (10,20,30,40μmol) pretreatment in a does-dependent manner, and it peaked at40μmol。But MG show significant cytotoxicity while the concentration continues to increase, and the cell activity decreased above50%at80μmol. HK also had a does-dependent and significant cell viability in a concentration of5,10,20μmol, and it peaked at20μmol。At the concentration of30μmol, HK has begun to exhibit inhibition of cell viability,40μmol concentration the cell viability inhibition rate reached above50%.2MG and HK showed significantly attenuated H2O2-induced oxidative damage of L02cells, and has a dose-dependent manner. Compared with the stress group, the vitality of the L02cells under stress were respectively increased by83%and63%with MG (40μmol) and HK (20μmol) pretreatment, higher than the tBHQ (80μmol) of40%, and MG antioxidant capacity stronger than HK. 3MG and HK failed to activate the Nrf2pathway in the hydrogen peroxide stress and non-stress conditions of L02cells.4MG (10-40μmol) and HK (5-20μmol) showed does-dependent manner significantly inhibited the hyperoside-mediated total level of p65protein increase, as well as significantly suppressed hyperoside-mediated p65protein nuclear translocation. Compared with the stress group, hyperoside-mediated total level of p65protein and p65protein nuclear translocation were respectively supperssed by45%and71%while MG (40μmol) pretreatment, and HK (20μmol) pretreatment resulted in supperssion rate of41%and59%.5MG and HK can significantly and does-dependently decreased the phosphorylation of H2O2-induced the IκB increased. Compared with the stress group, MG (40mmol) and HK (20mmol) pretreatment showed suppressed the phosphorylation protein levels of IκB by70%and33%, respectively.6MG and HK were significantly decreased the phosphorylation of p38, JNK1/2and ERK1/2protein in nomal L02cells, with a time-and does-dependent effect. MG (40mmol) and HK (20mmol) pretreatment12h on p-p38, p-JNK1/2p-ERK1/21inhibition rates were60%,49%,49%and64%,65%,59%,7MG can does-dependently reversed H2O2-induced MAPKs pathway activation. Compared with the stress group, MG (40mmol) and HK (20mmol) pretreatment showed significantly suppressed the increased of p-p38, p-JNK1/2, p-ERKl/2protein levels respectively by75%,77%,81%and27%,65%,86%;8MG and HK can does-dependently reversed H2O2-induced the protein levels of COX-2and iNOS increased. Compared with the stress group, MG (40mmol) and HK (20mmol) pretreatment showed significantly suppressed the COX-2protein levels respectively by77%and75%, as well as significantly suppressed the iNOS protein levels respectively by and87%and90%;Conclusion:Magnolol and Honokiol protects human hepatocytes from hydrogen peroxide-derived oxidative strss via the MAPKs/NfκB pathways
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