Abstract
Despite its deleterious effects on living cells, oxidative stress plays essential roles in normal physiological processes and provides signaling molecules for cell growth, differentiation, and inflammation. Macrophages are equipped with antioxidant mechanisms to cope with intracellular ROS produced during immune response, and Nrf2 (NF-E2-related factor 2)/HO-1 (heme oxygenase-1) pathway is an attractive target due to its protective effect against ROS-induced cell damage in inflamed macrophages. We investigated the effects of ethanol extract of A. villosum (AVEE) on lipopolysaccharide- (LPS-) stimulated inflammatory responses generated via the Nrf2/HO-1 signaling pathway in murine peritoneal macrophages and RAW 264.7 cells. AVEE was found to suppress the NF-κB signaling pathway, thus, to reduce proinflammatory cytokine, nitric oxide, and prostaglandin levels in peritoneal macrophages and Raw 264.7 cells treated with LPS, and to enhance HO-1 expression by activating Nrf2 signaling. Furthermore, these anti-inflammatory effects of AVEE were diminished when cells were pretreated with SnPP (a HO-1 inhibitor). HPLC analysis revealed AVEE contained quercetin, a possible activator of the Nrf2/HO-1 pathway. These results show A. villosum ethanol extract exerts anti-inflammatory effects by activating the Nrf2/HO-1 pathway in LPS-stimulated macrophages.
Highlights
Oxidative stress can be defined as an imbalance surfeit of ROS production as compared with ROS depletion by antioxidant defense systems [1]
We investigated the effects of an ethanol extract of A. villosum (AVEE) on LPS-stimulated murine peritoneal macrophages and Raw 264.7 cells and mechanisms responsible for these effects
Immunoblotting showed obvious changes in the localization of Nrf2 from cytoplasm to nuclei after 3 h of AVEE treatment (100 μg/mL) (Figure 4(c)). e results indicate AVEE treatment promoted the nuclear translocation of Nrf2 and activated the Nrf2/heme oxygenase-1 (HO-1) pathway to increase HO-1 level (Figure 4(d))
Summary
Oxidative stress can be defined as an imbalance surfeit of ROS (reactive oxygen species) production as compared with ROS depletion by antioxidant defense systems [1]. Despite their deleterious effects, ROS play crucial roles in the physiological processes and metabolisms of organisms that utilize oxygen [2, 3]. Excessive ROS induced by, for example, lead, carbon tetrachloride (CCl4), or LPS can activate MAPK and NF-κB pathways and initiate inflammatory responses [8,9,10,11]. Of these ROS inducing agents, LPS has been intensively studied in the context of inflammatory response progression in macrophages [12]
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