Quercetin and monochloropivaloylquercetin exerted a significant antioxidant effect by strengthening the antioxidant defense system via induced nuclear translocation of Nrf-2 and decreased Keap1 expression in addition to increased NQO1.
Nrf-2 is sequestered in the cytoplasm with its cytosolic repressor Keap1.
Furthermore, we also found that the protective effects of MaR 1 were inhibited by the HO-1 inhibitor, Znpp-IX, and the expression of HO-1 can be downregulated by Brusatol, an Nrf-2 transcription factor antagonist.
Representative Western blots and quantitative analyses showing nuclear Nrf-2 (a) and cytosolic HO-1 (b) protein expression in the lung.
Caption: Figure 6: MaR 1 upregulated HO-1 expression may be partly mediated by Nrf-2 activation.
These effects were achieved via upregulating Nrf-2 signaling pathway.
Currently, Nrf-2 is the key molecule which mediates the response of the endogenous antioxidant system.
In our study, the results showed that the gene transcription level of Nrf-2 was increased in the [H.sub.2][O.sup.2] group.
In conclusion, our study indicated that PCs could protect against the oxidative damage induced by [H.sub.2][O.sup.2] in TDSCs, and the cytoprotective effects might be achieved by the fact that PCs activated the expression of GCLM, HO-1, and NQO-1 via upregulating Nrf-2 signaling pathway.
Several studies have reported that nuclear translocation of activated Nrf-2 is an important upstream contributor to the mechanism of HO-1 expression in a wide variety of cells including endothelial cells.
From several lines of investigation, it is reported that natural products can promote dissociation of the Nrf-2-Keapl complex, leading to nuclear translocation of Nrf-2, resulting in the induction of some anti-inflammatory proteins including HO-1 (Yayeh et al.
In conclusion, sauchinone showed potent anti-vascular inflammatory effects on high glucose-induced endothelial cell activation, possibly through the Nrf-2 pathway-dependent expression of HO-1.