ABSTRACT
Cannabinoids (CBs) have recently been approved to exert broad anti-inflammatory activities in experimental models of multiple sclerosis (MS). It has been demonstrated that these compounds could also have effects on neurodegeneration, demyelination, and autoimmune processes occurring in the pathology of MS. However, the clinical use of CBs is limited by their psychoactive effects. Among cannabinoid compounds, cannabidiol (CBD) and palmitoylethanolamide (PEA) have no psychotropic activities. We induced experimental autoimmune encephalomyelitis (EAE), a model of MS, by injecting myelin oligodendrocyte glycoprotein (MOG) to C57BL/6 mice. We assessed the effects of CBD, PEA, and co-administration of CBD and PEA on neurobehavioral scores, immune cell infiltration, demyelination, axonal injury, and the expression of inflammatory cytokines by using histochemistry methods and real-time RT-PCR. Treatment with either CBD (5mg/kg) or PEA (5mg/kg) during disease onset reduced the severity of the neurobehavioral scores of EAE. This effect of CBD and PEA was accompanied by diminished inflammation, demyelination, axonal damage and inflammatory cytokine expression while concurrent administration of CBD (5mg/kg) and PEA (5mg/kg) was not as effective as treatment with either drug per se. These results suggest that, CBD and PEA, non-psychoactive CBs, attenuate neurobehavioral deficits, histological damage, and inflammatory cytokine expression in MOG-immunized animals. However, there is an antagonistic interaction between CBD and PEA in protection against MOG-induced disease.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Cannabidiol/pharmacology , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Ethanolamines/pharmacology , Palmitic Acids/pharmacology , Amides , Animals , Axons/drug effects , Axons/pathology , Axons/physiology , Drug Therapy, Combination , Encephalomyelitis, Autoimmune, Experimental/pathology , Encephalomyelitis, Autoimmune, Experimental/physiopathology , Female , Interferon-gamma/metabolism , Interleukin-17/metabolism , Macrophages/drug effects , Macrophages/pathology , Macrophages/physiology , Mice, Inbred C57BL , Microglia/drug effects , Microglia/pathology , Microglia/physiology , Myelin Sheath/drug effects , Myelin Sheath/pathology , Myelin Sheath/physiology , Neuroimmunomodulation/drug effects , Severity of Illness Index , Spinal Cord/drug effects , Spinal Cord/pathology , Spinal Cord/physiopathology , Treatment Outcome , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Present researchers studied the relation between insulin with free and total leptin in type 2 diabetic patients. Thirty non insulin dependent diabetic obese patients (age: 50 +/- 12 year and BMI>30 kg m(-2)) and thirty non insulin dependent diabetic non obese patients (age: 49 +/- 25 year and BMI<25 kg m(-2)) were studied. Free leptin was purified by Gel filtration Chromatography and the fractions were collected and then their free leptin was measured by a high sensitive ELISA Kit. Circulation total leptin and insulin were measured by ELISA. Circulation free and total leptin were significantly correlated to insulin (p < 0.005). Free leptin concentrations were higher in women than in men (p < 0.001). Ratio of free leptin to total in obese subjects is more than non-obese subjects (0.27 +/- 0.1 vs. 0.03 +/- 0.04, p < 0.001). Ratio of free to total leptin showed a positive correlations with insulin (r = 0.58, p < 0.001) insulin resistance (r = 31, p < 0.015) and BMI (r = 0.86, p < 0.001). The majority of leptin which circulates in obese individuals was free form. Presumably it is bioactive portion of hormone and thus obese subjects are resistant to free leptin. These observations are consistent with the view that free leptin levels in diabetes patients attributed to changes in serum insulin level and insulin resistant.
