Agrimonolide and Desmethylagrimonolide Induced HO-1 Expression in HepG2 Cells through Nrf2-Transduction and p38 Inactivation
نویسندگان
چکیده
Agrimonolide and desmethylagrimonolide are the main bioactive polyphenols in agrimony with well-documented antioxidant, anti-diabetic, and anti-inflammatory potential. We report here for the first time that agrimonolide and desmethylagrimonolide stimulate the expression of phase II detoxifying enzymes through the Nrf2-dependent signaling pathway. Agrimonolide and desmethylagrimonolide also possess considerable protective activity from oxidative DNA damage. In order to explore the cytoprotective potential of agrimonolide and desmethylagrimonolide on oxidative stress in liver, we developed an oxidative stress model in HepG2 cells, and check the hypothesis whether Nrf2 pathway is involved. Western blotting and luciferase assay revealed that exposure of HepG2 cells to agrimonolide or desmethylagrimonolide leads to increased heme oxygenase-1 (HO-1) expression by activating ARE through induction of Nrf2 and suppression of Kelch-like ECH-associated protein 1 (Keap1). Moreover, agrimonolide and desmethylagrimonolide also activated ERK signaling pathways and significantly attenuated individual p38 MAPK expression, subsequently leading to Nrf2 nuclear translocation. In conclusion, our results indicated that transcriptional activation of Nrf2/ARE is critical in agrimonolide and desmethylagrimonolide-mediated HO-1 induction, which can be regulated partially by the blockade of p38 MAPK signaling pathway and inhibiting nuclear translocation of Nrf2.
منابع مشابه
Homocysteine Induces Heme Oxygenase-1 Expression via Transcription Factor Nrf2 Activation in HepG2 Cells
Background: Elevated level of plasma homocysteine has been related to various diseases. Patients with hyperhomocysteinemia can develop hepatic steatosis and fibrosis. We hypothesized that oxidative stress induced by homocysteine might play an important role in pathogenesis of liver injury. Also, the cellular response designed to combat oxidative stress is primarily controlled by the transcripti...
متن کاملBilobalide ameliorates carbon tetrachloride-induced oxidative damage in HepG2 cells by the induction of Nrf2-dependent HO-1 expression through PI3K/Akt and P38 pathways
Oxidative stress is implicated in the pathogenesis of hepatic damage induced by various factors. Bilobalide (BB) is a compound extracted from Ginkgo biloba leaf. It has been reported for its anti-oxidative activity and has been tested to treat brain damage. However, it has not been studied whether BB possesses hepatoprotective activity though regulating heme oxygenase-1 (HO-1) which is a key an...
متن کاملCasein Glycomacropeptide Hydrolysates Exert Cytoprotective Effect against Cellular Oxidative Stress by Up-Regulating HO-1 Expression in HepG2 Cells
Oxidative stress is considered as an important mediator in the progression of metabolic disorders. The objective of this study was to investigate the potential hepatoprotective effects and mechanisms of bovine casein glycomacropeptide hydrolysates (GHP) on hydrogen peroxide (H₂O₂)-induced oxidative damage in HepG2 cells. Results showed that GHP significantly blocked H₂O₂-induced intracellular r...
متن کاملQuercetin modulates Nrf2 and glutathione-related defenses in HepG2 cells: Involvement of p38.
Dietary flavonoid quercetin has been suggested as a cancer chemopreventive agent, but the mechanisms of action remain unclear. This study investigated the influence of quercetin on p38-MAPK and the potential regulation of the nuclear transcription factor erythroid-2p45-related factor (Nrf2) and the cellular antioxidant/detoxifying defense system related to glutathione (GSH) by p38 in HepG2 cell...
متن کاملInduction of Heme Oxygenase-1 Inhibits Cell Death in Crotonaldehyde-Stimulated HepG2 Cells via the PKC-δ -p38 -Nrf2 Pathway
BACKGROUND Crotonaldehyde, an alpha, beta-unsaturated aldehyde present in cigarette smoke, is an environmental pollutant and a product of lipid peroxidation. It also produces adverse effects to humans and is considered as a risk factor for various diseases. Heme oxygenase-1 (HO-1) plays important roles in protecting cells against oxidative stress as a prime cellular defense mechanism. However, ...
متن کامل