The modulatory effects of luteolin on cyclic AMP/Ciliary neurotrophic factor signaling pathway in experimentally induced autoimmune encephalomyelitis

• Published in: IUBMB life 2019-09, Vol.71 (9), p.1401-1408
• Main Authors: El‐Deeb, Omnia Safwat, Ghanem, Heba Bassiony, El‐Esawy, Rasha Osama, Sadek, Mona Tayssir
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Apoptosis; cAMP; Caspase; Caspase 3 - genetics; Caspase-3; Central nervous system; Chemokine CCL3 - genetics; Ciliary neurotrophic factor; Ciliary Neurotrophic Factor - genetics; Cyclic AMP; Cyclic AMP - genetics; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental - drug therapy; Encephalomyelitis, Autoimmune, Experimental - genetics; Encephalomyelitis, Autoimmune, Experimental - pathology; Enzyme-linked immunosorbent assay; Etiology; Experimental allergic encephalomyelitis; experimental autoimmune encephalomyelitis; Flavonoids; Gene expression; Gene Expression Regulation - genetics; Humans; Inflammation; Inoculum; luteolin; Luteolin - pharmacology; Macrophage inflammatory protein; Macrophage inflammatory protein 1; Multiple sclerosis; Multiple Sclerosis - drug therapy; Multiple Sclerosis - genetics; Multiple Sclerosis - pathology; Myelin; NF‐κB; Oligodendrocyte-myelin glycoprotein; Rats; Signal Transduction
• ISSN: 1521-6543; 1521-6551
• DOI: 10.1002/iub.2099

Multiple sclerosis (MS) is considered to be an autoimmune disorder of the central nervous system (CNS) manifested by chronic inflammation. Although its etiology is not completely understood, inflammation and apoptosis are known to be major players involved in its pathogenesis. Luteolin, the naturally occurring flavonoid, is known by strong antioxidant and anti‐inflammatory properties, yet research studies about its therapeutic role in MS are still lacking. The study aimed to provide insight into effects of luteolin in experimental autoimmune encephalomyelitis (EAE) by monitoring inflammatory, apoptotic, and antioxidant biochemical parameters in addition to histological examination findings. The study included 45 adult female Wistar rats allocated to three equal groups: (a) group I: control group, (b) group II: EAE group, EAE was induced by single intradermal injection of 0.2 mL inoculum comprising 20‐μg recombinant rat myelin oligodendrocyte glycoprotein (MOG), and (c) group III: luteolin‐treated EAE group, luteolin was given in a dose of 10 mg/kg/day, i.p. All groups were subjected to assessment of brain ciliary neurotropic factor (CNTF) mRNA gene expression and measurement of cleaved caspase 3, nuclear factor kappa B (NF‐κB), cyclic AMP (cAMP), and macrophage inflammatory protein 1 alpha (MIP‐1α) by the ELISA technique, total antioxidant capacity (TAC) level is assessed spectrophotometrically. Compared with the EAE group, luteolin‐treated EAE group showed upregulation of CNTF expression and significant increase in cAMP and TAC levels, while it showed significant decrease in cleaved caspase 3, NF‐κB, and MIP‐1α levels. Based on our data herein, luteolin may provide a promising preclinical therapeutic line in MS being anti‐inflammatory, antiapoptotic, and neurotrophic agent. © 2019 IUBMB Life, 71(9):1401–1408, 2019