Abstract
Sulfuretin is one of the major flavonoid components in Rhus verniciflua Stokes (Anacardiaceae) isolates. In this study, we investigated the protective effects of sulfuretin against tert-butyl hydroperoxide (t-BHP)-induced oxidative injury. The results indicated that the addition of sulfuretin before t-BHP treatment significantly inhibited cytotoxicity and reactive oxygen species (ROS) production in human liver-derived HepG2 cells. Sulfuretin up-regulated the activity of the antioxidant enzyme heme oxygenase (HO)-1 via nuclear factor E2-related factor 2 (Nrf2) translocation into the nucleus and increased the promoter activity of the antioxidant response element (ARE). Moreover, sulfuretin exposure enhanced the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase 1/2 (ERK1/2), which are members of the mitogen-activated protein kinase (MAPK) family. Furthermore, cell treatment with a JNK inhibitor (SP600125) and ERK inhibitor (PD98059) reduced sulfuretin-induced HO-1 expression and decreased its protective effects. Taken together, these results suggest that the protective effect of sulfuretin against t-BHP-induced oxidative damage in human liver-derived HepG2 cells is attributable to its ability to scavenge ROS and up-regulate the activity of HO-1 through the Nrf2/ARE and JNK/ERK signaling pathways. Therefore, sulfuretin could be advantageous as a bioactive source for the prevention of oxidative injury.
Highlights
Oxidative stress develops from an imbalance between the systems generating and scavenging reactive oxygen species (ROS)
The competitive inhibitor of heme oxygenase (HO) activity, SnPP, significantly suppressed sulfuretin-mediated cell protection and ROS deduction (Figure 4). These results suggested that HO-1 expression by sulfuretin is related to the protective effect and ROS-scavenging activity in HepG2 cells
We provided evidence to support the view that HO-1 expression, one of the key phase II detoxifying enzymes, through nuclear factor E2-related factor 2 (Nrf2) signaling pathways plays a key role in mediating the hepatoprotective effects of sulfuretin
Summary
Oxidative stress develops from an imbalance between the systems generating and scavenging reactive oxygen species (ROS). The complex is disrupted by exposure to various stimuli, and free Nrf subsequently translocates into the nucleus and forms heterodimers with small Maf proteins and up regulates via interaction with antioxidant response element (ARE) [8,9]. This results in the induction of gene expression of phase II enzymes, including HO-1 [10]. Many studies use tert-butyl hydroperoxide (t-BHP) as the toxic agent to investigate the antioxidant effects in human liver-derived HepG2 cells [15,16]. We investigated the hepatoprotective effect of sulfuretin and the mechanism involved in this action in human liver-derived HepG2 cells stimulated with t-BHP
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