Neuroprotective Effect of Coumarin Nasal Formulation: Kindling Model Assessment of Epilepsy

Abstract

Epilepsy is a brain disorder characterized by sudden recurrent seizures. Considering the fact that epileptogenesis is a process that affects the quality of life, our goal is to delay the process of epileptogenesis and to increase the latency of epileptic attacks, offering better quality of life to patients. Traditional system of medicines has a promise in some of the medicines, which have been used for the treatment of epilepsy. One such medicinal plant is Eclipta alba (EA). According to Ayurvedic philosophy, the juice of leaves of EA is pounded with garlic and pepper for the treatment of epilepsy. Taking clue from the Ayurvedic system of medicines, we formulated coumarin fraction of EA, namely, coumarin nasal formulation (CNF) for its nasal delivery. CNF was analyzed by using high performance liquid chromatography (HPLC) and ultraviolet absorption spectroscopy for its drug content determination. In vitro drug release studies were performed in simulated nasal electrolyte solution (SNES) maintaining constant pH of 5.5 at 37°C. Irritation by CNF was evaluated using hen’s egg test chorioallantoic membrane (HET-CAM) assay. Formulation was found to be non-irritant in HET-CAM assay. CNF was further assessed in vivo by measuring the progress and attainment of pentylenetetrazole (PTZ) kindling in mice. Neuronal changes were assessed by hematoxylin and eosin (H&E) and Nissl staining technique. Glial fibrillary acidic protein (GFAP) a neuroinflammatory marker and tumor necrosis factor alpha (TNF-α) an inflammatory marker were also measured. CNF (10 mg/kg, nasal route) when given as a pretreatment lowered seizure score and delayed the progression of seizure similar to diazepam. CNF decreased the PTZ induced oxidative damage, TNF-α as well as GFAP levels in the midbrain tissue particularly in hippocampus region. The results suggest that CNF may be a promising therapeutic approach to offer protection from sudden recurrent seizures alone or in combination with current drugs in management of epilepsy.

The comparison of inflammatory markers in pentylenetetrazole-induced acute epileptic seizure model and chronic epilepsy model in rats

“…In this study, we show that there is increase in IL-1β levels chronic PTZ models in the cortex (Figure 2 Show that IL-1β may be associated with the both epileptic seizure and epileptogenesis. Our findings of IL-1β levels in acute and chronic PTZ models is consistent one of the previous studies which are carried out in rat and mice brain [15,20,23]. According to our findings, it may be suggested that TNF-α is assotiated with epileptogenesis, while IL-1β is related to both acute seizure and epileprogenesis.…”

“…Moreover, our findings of TNF-α levels in chronic PTZ models is consistent of the previous study performed in both mice and rat chronic PTZ models in hippocampus [18,19]. However, in contrast to our study, one of the study heve suggested that there is no changing in TNFα levels in hippocampus after chronic PTZ model [20,21]. It can be explained the collecting time of tissues after last PTZ injection.…”

Natural products isolated from Casimiroa

“…They are simple coumarins, furano coumarins, dihydrofurano coumarins, pyrano coumarins (linear and angular types), phenyl coumarins, and bicoumarins [39][40][41]. Coumarin is a plant-derived natural product known for its pharmacological properties such as anti-inflammatory [42,43], antibacterial [42], anticoagulant [44], antifungal [45,46], antiviral [47,48], anticancer [49][50][51], antidiabetic [52,53], antihypertensive [54], anticonvulsant [55], antioxidant [56][57][58][59], antimicrobial [60], and neuroprotective properties [61]. Casimiroa is the abundant source of coumarins.…”

“…[97] Another important study was performed on the antioxidant activity of fractions and isolated compounds (43,54,55, and 56) from leaves of C. edulis. Ethanol fraction was exhibited the more potent antioxidant activity (842 μM Trolox equivalents/g dry weight) [26].…”

Histopathological and Biochemical Assessment of Neuroprotective Effects of Sodium Valproate and Lutein on the Pilocarpine Albino Rat Model of Epilepsy

“…Epilepsy is one of the most common neurological disorders. Intermittent episodes of exaggerated, atypical cerebral activity give rise to the clinical features, ranging from debilitating fits, cerebral processing abnormalities, and mental health issues to the life-threatening clinical syndrome of status epilepticus (SE) [ 1 ]. The World Health Organization (WHO) figures indicate that epilepsy has a global incidence of 2.4 million and a prevalence of 50 million, affecting individuals regardless of age.…”