The importance of both NRF2 and p62-dependent autophagy in SPD-mediated liver protection was confirmed using a carbon tetrachloride-induced liver fibrosis model in wild-type, Nrf2<sup>-/-</sup> , p62<sup>-/-</sup> and Nrf2<sup>-/-</sup> ;p62<sup>-/-</sup> mice, as the protective effect of SPD was significantly reduced in NRF2 or p62 single knockout mice, and completely abolished in the double knockout mice.
Our results showed that TP supplementation alleviated liver morphology, liver function and liver fibrosis; improved oxidative stress parameters; and increased the expression of STAT5b, Nrf2, HO-1 and NQO-1 and decreased the expression of Keap1 in the liver tissues of aged rats.
In summary, Nrf2 is critically involved in preventing liver fibrosis induced by long-term administration of APAP in mice, and Andro alleviates APAP-induced liver fibrosis by attenuating liver oxidative stress injury via inducing Nrf2 activation.
Taken together, activation of I<sub>1</sub>R negatively regulates the progression of liver fibrosis in the Nrf2-dependent pathway, which suggests that specifically targeting I<sub>1</sub>R may be a potential therapeutic strategy for the treatment of liver fibrosis.
The aim of the present study was to investigate the effect of XCHT on liver fibrosis and focuse on the Nrf2 pathway in the protection of XCHT against CCl<sub>4</sub>-induced oxidative stress.
In in vivo system, Nrf2 knockdown mediated by Nrf2 shRNA lentivirus not only accelerated the lipid degradation in HSCs but also promoted the progression of CCl<sub>4</sub>-induced hepatic fibrosis in mice.
In this study, we found that the expression and activity of nuclear factor (erythroid-derived 2) - like 2 (Nrf2) were decreased in activated HSCs and negatively correlated with hepatic fibrosis severity in human liver specimens.
This study demonstrates that Sch B prevents the progression of liver fibrosis by the regulation of Nrf2-ARE and TGF-β/Smad signaling pathways, and indicates that Sch B can be used for the treatment of liver fibrosis.
Hyperoside increased the activity of the antioxidant and phase II detoxifying enzymes through the activation of Nrf2 nuclear translocated in the CCl<sub>4</sub>-induced liver fibrosis mice.
More importantly, this genomic analysis of nano-TiO2 treated HepG2 cells linked some of the in vitro canonical pathways to in vivo adverse outcomes: NRF2-mediated response pathways to oxidative stress, acute phase response to inflammation, cholesterol biosynthesis to steroid hormones alteration, fatty acid metabolism changes to lipid homeostasis alteration, G2/M cell checkpoint regulation to apoptosis, and hepatic fibrosis/stellate cell activation to liver fibrosis.
Cirrhotic rats treated with simvastatin or Ad-KLF2 showed hepatic upregulation in the KLF2-Nrf2 pathway, deactivation of HSC and prominent reduction in liver fibrosis.
Collectively, these results show that SFN elicits an antifibrotic effect on hepatic fibrosis through Nrf2-mediated inhibition of the TGF-β/Smad signaling and subsequent suppression of HSC activation and fibrogenic gene expression.