Olive Leaf Polyphenols Attenuate the Clinical Course of Experimental Autoimmune Encephalomyelitis and Provide Neuroprotection by Reducing Oxidative Stress, Regulating Microglia and SIRT1, and Preserving Myelin Integrity

Abstract

Numerous evidences suggest that plant polyphenols may have therapeutic benefits in regulating oxidative stress and providing neuroprotection in many neurodegenerative diseases, including multiple sclerosis (MS). However, these mechanisms are not yet completely understood. In this study, we investigated the effect of olive leaf polyphenols on oxidative stress through oxidation marker level and activity (TBARS, SOD, and GPX) and their protein expression (SOD1, SOD2, and GPX1), as well as the protein expression of Sirtuin 1 (SIRT1) and microglia markers (Iba-1, CD206, and iNOS) and myelin integrity (proteolipid protein expression) in the brain of rats with induced experimental autoimmune encephalomyelitis (EAE) and subjected to olive leaf therapy. Experiments were performed in male EAE DA rats, which were randomly divided into 2 main groups: EAE groups treated with the therapy of olive leaf (EAE+TOL) and untreated EAE control groups. The EAE treated groups consumed olive leaf tea instead of drinking water (ad libitum) from the beginning to the end of the experiment. In addition, olive leaf extract was injected intraperitoneally (i.p.) for the 10 continuous days and started on the 8th day after EAE induction. The clinical course was monitored in both groups until the 30th day after EAE induction. Our results demonstrated that TOL attenuated the clinical course of EAE; reduced the oxidative stress (by decreasing the concentration of MDA); upregulated antioxidant enzymes (SOD1, SOD2, and GPX1), SIRT1 (overall and microglial), and anti-inflammatory M2 microglia; downregulated proinflammatory M1 type; and preserved myelin integrity. These data support the idea that TOL may be an effective therapeutic approach for treating MS and other neurodegenerative diseases.

SIRT1 Promotes M2 Microglia Polarization via Reducing ROS-Mediated NLRP3 Inflammasome Signaling After Subarachnoid Hemorrhage

“…According to current literature, SIRT1 can modulate the microglia polarization shift from the M1 phenotype and skew toward the M2 phenotype in a variety of disorders (22,24,33,41). A previous study by Chen et al reported that SIRT1 activation by SRT1720 significantly improved functional recovery after SCI by reducing the levels of proinflammatory cytokines, and the number of M1 macrophages (33).…”

The Role of Nutritional Lifestyle and Physical Activity in Multiple Sclerosis Pathogenesis and Management: A Narrative Review

“…Moreover, the beneficial effects of the MD appear to derive in part from the availability of polyphenols in foods, as suggested by the fact that in a rat model, dietary supplementation with olive leaf extract, which possesses large amounts of polyphenols, led to an observed reduced severity of EAE [99].…”

Gender-Related Differences in BMP Expression and Adult Hippocampal Neurogenesis within Joint-Hippocampal Axis in a Rat Model of Rheumatoid Arthritis

“…The control group was treated with physiological saline solution and was sacrificed after a few days. Rats were sacrificed by exsanguination in deep anaesthesia, which was induced by a combination of ketamine (80 mg/kg) and xylazine (5 mg/kg) that were administered by intraperitoneal injection, as previously described [28,29]. All experiments were performed according to the guidance of the European Community Council Directive (86/609/EEC) and the recommenda-tions of the National Centre for the Replacement, Refinement and Reduction of Animals in Research.…”

“…The photomicrographs were taken and examined under an Olympus BX51 light microscope equipped with an Olympus DP70 camera (Olympus, Japan). The immunohistochemical/fluorescence staining quantification of protein expression was performed on 4 µm tissue sections from paraffin-embedded tissues of the brain and hind paws using Cell F v3.1 software (Olympus Soft Imaging Solutions), as previously described [28]. Captured images were subjected to intensity separation.…”

“…DCX + , SOX + , and Ki67 + cells were counted manually in an image surface area of 0.053 mm 2 and at a magnification of 400×. Results were expressed as a mean number of cells per mm 2 [28,31].…”