Oleuropein Has Modulatory Effects on Systemic Lipopolysaccharide-Induced Neuroinflammation in Male Rats
No Thumbnail Available
Date
2024
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Background: Neuroinflammation induced by systemic inflammation is a risk factor for developing chronic neurologic disorders. Oleuropein (OLE) has antioxidant and anti-inflammatory properties; however, its effect on systemic inflammation-related neuroinflammation is unknown. Objectives: This study aimed to determine whether OLE protects against systemic lipopolysaccharide (LPS)-induced neuroinflammation in rats. Methods: Six-wk-old Wistar rats were randomly assigned to 1 of the following 5 groups: 1) control, 2) OLE-only, 3) LPS + vehicle, 4) OLE+LPS (O-LPS), and 5) a single-dose OLE + LPS (SO-LPS group). OLE 200 mg/kg or saline as a vehicle was administered via gavage for 7 d. On the seventh day, 2.5 mg/kg LPS was intraperitoneally administered. The rats were decapitated after 24 h of LPS treatment, and serum collection and tissue dissection were performed. The study assessed astrocyte and microglial activation using glial fibrillary acidic protein (GFAP) and CD11b immunohistochemistry, nod-like receptor protein-3, interleukin (IL)-1β, IL-17A, and IL-4 concentrations in prefrontal and hippocampal tissues via enzyme-linked immunosorbent assay, and total antioxidant/oxidant status (TAS/TOS) in serum and tissues via spectrophotometry. Results: In both the O-LPS and SO-LPS groups, LPS-related activation of microglia and astrocytes was suppressed in the cortex and hippocampus (P < 0.001), excluding cortical astrocyte activation, which was suppressed only in the SO-LPS group (P < 0.001). Hippocampal GFAP immunoreactivity and IL-17A concentrations in the dentate gyrus were higher in the OLE group than those in the control group, but LPS-related increases in these concentrations were suppressed in the O-LPS group. The O-LPS group had higher cortical TAS and IL-4 concentrations. Conclusions: OLE suppressed LPS-related astrocyte and microglial activation in the hippocampus and cortex. The OLE-induced increase in cortical IL-4 concentrations indicates the induction of an anti-inflammatory phenotype of microglia. OLE may also modulate astrocyte and IL-17A functions, which could explain its opposing effects on hippocampal GFAP immunoreactivity and IL-17A concentrations when administered with or without LPS. © 2024 American Society for Nutrition
Description
Keywords
Animals , Anti-Inflammatory Agents , Antioxidants , Hippocampus , Inflammation , Interleukin-17 , Interleukin-1beta , Interleukin-4 , Iridoid Glucosides , Lipopolysaccharides , Male , Microglia , Neuroinflammatory Diseases , Rats , Rats, Wistar , CD11b antigen , cryopyrin , glial fibrillary acidic protein , hydrogen peroxide , interleukin 17 , interleukin 1beta , interleukin 4 , oleuropein , antiinflammatory agent , antioxidant , interleukin 17 , interleukin 1beta , interleukin 4 , iridoid , lipopolysaccharide , oleuropein , animal experiment , animal model , animal tissue , antibody labeling , antioxidant activity , Article , astrocyte , colorimetry , controlled study , dentate gyrus , enzyme linked immunosorbent assay , female , granular cell , hippocampal CA3 region , hippocampal tissue , hippocampus , immunity , immunohistochemistry , immunoreactivity , lipopolysaccharide-induced neuroinflammation , male , microglia , nonhuman , oxidation reduction state , prefrontal cortex , rat , spectrophotometry , stratum pyramidale , thin layer chromatography , animal , inflammation , metabolism , nervous system inflammation , Wistar rat