Background Nrf2-Bach1 antioxidant signaling pathway is considered as one of the most important mechanisms of cellular resistance to oxidative injury. The effect of hyperoside (Hyp) on the expression and distribution of Bach1, the relationship of Hyp’s antioxidative effect and the influence of Bach1 remains unclear. Purpose The aim of this study was to investigate the role and mechanisms of Bach1 in the protective effect of Hyp on oxidative liver injury. Methods The protective effect of Hyp on oxidative stress injury was observed in vivo and in vitro. Next, the influence of Hyp on Bach1 expression and distribution, and competitive combination of Nrf2-Bach1 with ARE in H 2 O 2 -induced L02 cell was studied by Western blot, RT-PCR, immunofluorescence and CHIP assay. Finally, the expressions of Crm1, ERK and p38 and their roles on Hyp mediated nuclear export of Bach1 were investigated by Western blot. Results Hyp ameliorated the pathological damage, reduced the liver index, AST, ALT and MDA activities, and increased SOD and GSH levels in the CCl 4 -induced acute liver injury mouse model. Hyp attenuated H 2 O 2 -induced oxidative stress injury in L02 cells. Hyp promoted the early rapid redistribution of Bach1 from nucleus to cytoplasm. CHIP analyses demonstrated that Hyp enhanced the levels of Nrf2-ARE complex, and weakened the levels of Bach1-ARE complex within three hours. In addition, Hyp enhanced transport protein Crm1 expression and ERK1/2 activity. And LMB, a Crm1 inhibitor, attenuated the effect of Hyp on Bach1 nuclear export and anti-oxidation. U0126, an ERK1/2 inhibitor, reduced the effect of Hyp on Crm1 expression and the Bach1 redistribution. Conclusion The hepatoprotective mechanism of Hyp was related to improve Bach1 nuclear export depending on ERK1/2-Crm1 to upregulate the level of Nrf2 binding to ARE.

Introduction: As a traditional Chinese medicine (TCM), Curculigo orchioides Gaertn. (Xianmao) has been widely used to treat bone-related diseases. However, the active components of this TCM, and the specific mechanisms by which it exerts effect, have yet to be elucidated. To identify potential targets for orcinol glucoside (OG), an active constituent of C. orchioides, during the treatment of osteoporosis (OP) by adopting a network pharmacology approach. Methods: First, we mined the Similarity ensemble approach (SEA), SwissTargetPrediction, DisGeNET, and Genecards databases were mined for data related to the prediction of OG- and OP-related targets. Next, we identified the common targets for OG and OP, and then used STRING software to create a protein-protein interaction (PPI) network. Then, we used topological analysis to identify which of the common targets were most significant. Then, we used the common significant targets and g:profiler to perform gene ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes ( KEGG) pathway enrichment analysis. Finally, we used molecular docking to predict the targets of OG that were most relevant to the treatment of OP and investigated the potential pharmacological mechanisms that might be involved. Results: In total, 130 potential targets of OG, and 4582 targets relevant to OP, were subjected to network analysis. There were 73 common targets; these identified the principal pathways linked to OP. In addition, topological analysis identified 14 key targets. Most of the predicted targets played crucial roles in the PI3K-AKT signaling pathway. Molecular docking identified ten core targets (VEGFA, IL6, EGFR, MAPK1, HRAS, CCND1, FGF2, IL2, MCL1 and CDK4), thus indicating that OG may promote osteoblast proliferation and differentiation by accelerating progression of the cell cycle.Conclusions: This research provides a theoretical base for identifying the specific potential mechanisms of OG in treatment of OP.