Resveratrol Protects Hippocampal Astrocytes Against LPS-Induced Neurotoxicity Through HO-1, p38 and ERK Pathways

Abstract

Resveratrol, a phytoalexin found in grapes and wine, exhibits antioxidant, anti-inflammatory, anti-aging and antitumor activities. Resveratrol also protects neurons and astrocytes in several neurological disease models. Astrocytes are responsible for modulating neurotransmitter systems, synaptic information, ionic homeostasis, energy metabolism, antioxidant defense and inflammatory response. In previous work, we showed that resveratrol modulates important glial functions, including glutamate uptake, glutamine synthetase activity, glutathione (GSH) levels and inflammatory response. Furthermore, astrocytes express toll-like receptors that specifically recognize lipopolysaccharide (LPS), which has been widely used to study experimentally inflammatory response. In this sense, LPS may stimulate pro-inflammatory cytokines release and oxidative stress. Moreover, there is interplay between these signals through signaling pathways such as NFκB, HO-1 and MAPK. Thus, here, we evaluated the effects of resveratrol on LPS-stimulated inflammatory response in hippocampal primary astrocyte cultures and the putative role of HO-1, p38 and ERK pathways in the protective effect of resveratrol. LPS increased the levels of TNF-α, IL-1β, IL-6 and IL-18 and resveratrol prevented these effects. Resveratrol also prevented the oxidative and nitrosative stress induced by LPS as well as the decrease in GSH content. Additionally, we demonstrated the involvement of NFκB, HO-1, p38 and ERK signaling pathways in the protective effect of resveratrol, providing the first mechanistic explanation for these effects in hippocampal astrocytes. Our findings reinforce the neuroprotective effects of resveratrol, which are mainly associated with anti-inflammatory and antioxidant activities.

The Essential Oils of Rhaponticum carthamoides Hairy Roots and Roots of Soil‐Grown Plants: Chemical Composition and Antimicrobial, Anti‐Inflammatory, and Antioxidant Activities

“…Lipopolysaccharide (LPS) is the main component of the outer membrane of Gram-negative bacteria and is known as an inductor of inflammation in various cells, including astrocytes [33]. LPS is recognized by Toll-like receptor 4 (TLR4) of astrocytes and the LPS treatment of astrocytes resulting in activation of transcription factor (NF- κ B) and mitogen-activated protein kinase (MAPK) which lead to the release of such inflammatory mediators as pro- and anti-inflammatory cytokines or the tumor necrosis factor (TNF- α ) or the overproduction of reactive oxygen species (ROS) [33].…”

“…LPS is recognized by Toll-like receptor 4 (TLR4) of astrocytes and the LPS treatment of astrocytes resulting in activation of transcription factor (NF- κ B) and mitogen-activated protein kinase (MAPK) which lead to the release of such inflammatory mediators as pro- and anti-inflammatory cytokines or the tumor necrosis factor (TNF- α ) or the overproduction of reactive oxygen species (ROS) [33]. Oxidative stress and inflammation are connected with many neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, multiple sclerosis, and other nervous pathogeneses [7].…”

“…Oxidative stress and inflammation are connected with many neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, multiple sclerosis, and other nervous pathogeneses [7]. Many studies have previously reported LPS induction of various inflammatory mediators in astrocytes [32, 33, 35]. …”

“…Many studies have also indicated that natural plant secondary metabolites may be used for the prevention of inflammation and oxidative damage-related neurodegenerative diseases [33, 35, 36]. In order to determine the anti-inflammatory effects of essential oils from R. carthamoides hairy roots and roots of soil-grown plants, astrocytes were treated with HR and SGR essential oils and stimulated by LPS for 24 h. It was found that HR and SGR essential oils possessed anti-neuroinflammatory activity and were able to suppress the levels of IL-1 β , IL-6, and TNF- α in LPS-stimulated astrocytes.…”

Guanosine inhibits LPS-induced pro-inflammatory response and oxidative stress in hippocampal astrocytes through the heme oxygenase-1 pathway

“…This protocol was in accordance with Bellaver et al, 2014 and 2015 [37,38]. Briefly, the newborn male Wistar rats' hippocampi were aseptically removed from cerebral hemispheres.…”