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

Abstract

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

Potential Utility of Natural Products against Oxidative Stress in Animal Models of Multiple Sclerosis

“…cAMP levels were decreased in the cerebrospinal fluids of MS patients, and inhibition of the cAMP/CREB signaling axis attenuated CNTF expression. Compared to EAE mice, luteolin-treated EAE mice demonstrated improved clinical motor function, reduced inflammatory infiltration of brain tissues, upregulated ciliary neurotrophic factor (CNTF) expression, significantly increased levels of cAMP and total antioxidant capacity (TAC) of the brain and significantly reduced levels of cleaved caspase 3, nuclear factor kappa-B (NF-κB) and macrophage inflammatory protein (MIP)-1α [ 142 ].…”

Paving Luteolin Therapeutic Potentialities and Agro‐Food‐Pharma Applications: Emphasis on In Vivo Pharmacological Effects and Bioavailability Traits

“…In another study, the luteolin's effect on neuroinflammation, oxidative stress, synaptic plasticity, and impaired cognitive impairment was tested on adult Sprague Dawley rats and it was determined that luteolin reduced chronic cerebral hypoperfusion-induced microglia overactivation along with other benefits [ 47 ]. Moreover, a study conducted by El-Deeb et al focused on investigating luteolin's effect on autoimmune encephalomyelitis showed that flavone has anti-inflammatory, antiapoptotic, and antineurotrophic activities also in multiple sclerosis [ 48 ].…”

Role of Plant-Derived Natural Compounds in Experimental Autoimmune Encephalomyelitis: A Review of the Treatment Potential and Development Strategy

“…Lut is neuroprotective in various diseases including epilepsy, autism spectrum disorders, Alzheimer’s disease, Parkinson’s disease, traumatic brain injury, and MS ( Nabavi et al, 2015a ). Oral administration and intraperitoneal injection are the main administration routes for Lut for a number of disorder models ( El-Deeb et al, 2019 ; Imran et al, 2019 ). The dosages of Lut range from 1.2 to 50 mg/kg, and in vivo studies have verified that it has a significant effect in alleviating various diseases such as cancer and MS ( El-Deeb et al, 2019 ; Imran et al, 2019 ).…”

“…Oral administration and intraperitoneal injection are the main administration routes for Lut for a number of disorder models ( El-Deeb et al, 2019 ; Imran et al, 2019 ). The dosages of Lut range from 1.2 to 50 mg/kg, and in vivo studies have verified that it has a significant effect in alleviating various diseases such as cancer and MS ( El-Deeb et al, 2019 ; Imran et al, 2019 ). Lut promotes ciliary neurotrophic factor (CNTF) expression and has the ability to increase cAMP and the total antioxidant capacity.…”

“…Lut promotes ciliary neurotrophic factor (CNTF) expression and has the ability to increase cAMP and the total antioxidant capacity. Also, Lut can decrease TNF and IL-1 expression through the NF-κb signaling pathway in EAE ( El-Deeb et al, 2019 ).…”