Oleuropein Has Modulatory Effects on Systemic Lipopolysaccharide-Induced Neuroinflammation in Male Rats

• Published in: The Journal of nutrition 2024-04, Vol.154 (4), p.1282-1297
• Main Authors: Şahin, Sevim, Şahin, Elif, Esenülkü, Gülnur, Renda, Gülin, Gürgen, Seren Gülşen, Alver, Ahmet, Abidin, İsmail, Cansu, Ali
• Format: Article
• Language: English
• Subjects: Anti-inflammatory agents; Antioxidants; astrocyte; Astrocytes; blood serum; CD11b antigen; cortex; Cytokines; Dentate gyrus; Diet; dissection; Enzyme-linked immunosorbent assay; Glial fibrillary acidic protein; Hippocampus; IL-17A; IL-4; immune response; Immunohistochemistry; Inflammation; Interleukin 4; interleukin-17; Lipopolysaccharides; males; Microglia; neuroinflammation; nutrition; Oleuropein; Oxidants; Oxidizing agents; phenotype; Phenotypes; Proteins; Risk factors; Rodents; Spectrophotometry; spectroscopy
• ISSN: 0022-3166; 1541-6100; 1541-6100
• DOI: 10.1016/j.tjnut.2024.02.017

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. This study aimed to determine whether OLE protects against systemic lipopolysaccharide (LPS)-induced neuroinflammation in rats. 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. 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. 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.