Abstract
Cissus quadrangularis (C. quadrangularis) is a plant of the Vitaceae family known for its anticonvulsant effects in traditional medicine. The objective of this study was to elucidate the anxiolytic and antiepileptic effects of aqueous extract of C. quadrangularis. The mice were divided into different groups and treated for seven consecutive days as follows: a negative control group that received distilled water, po, four test groups that received four doses of the plant (37.22, 93.05, 186.11, and 372.21 mg/kg, po), and a positive control group that received sodium valproate (300 mg/kg, ip). One hour after the first treatment (first day), epilepsy was induced by intraperitoneal administration of a single dose of pilocarpine (360 mg/kg). On the seventh day, the anxiolytic effects of the extract were evaluated in the epileptic mice using the elevated plus maze (EPM) and open field (OP) paradigms. Antioxidant activities and the involvement of gabaergic neurotransmission were determined by measuring the levels of malondialdehyde, reduced glutathione (GSH), GABA, and GABA-transaminase (GABA-T) in the hippocampus of sacrificed epileptic mice. The results show that the extract of C. quadrangularis significantly and dose-dependently increased the latency to clonic and generalized tonic–clonic seizures and decreased the number and duration of seizures. In the EPM, the extract of C. quadrangularis significantly increased the number of entries and the time spent into the open arms and reduced the number of entries and the time spent into the closed arms as well as the number of rearing. The extract of C. quadrangularis also increased the number of crossing, and the time spent in the center of the OP. The level of MDA and the activity of GABA-T were significantly decreased by the extract of C. quadrangularis while reduced GSH and GABA levels were increased. The results suggest that the anticonvulsant activities of C. quadrangularis are accompanied by its anxiolytics effects. These effects may be supported by its antioxidant properties and mediated at least in part by the GABA neurotransmission.
Highlights
Status epilepticus (SE) is the first manifestation of epilepsy in approximately 50% of patients (Chapman et al, 2001)
Latency to First Clonic and Tonic–Clonic Seizures 24 h After Status Epilepticus It appears that the time of onset of the first clonic and tonic– clonic seizures in mice in the DW + Pilo groups (4 and 43 s, respectively) are not significant compared to the DW + DW group
This study aimed to show antiepileptogenic and anticonvulsant effects of C. quadrangularis accompanied by its anxiolytic effects since anxiety is developed in epileptic patients (Robertson et al, 1987; Torta and Keller, 1999; Mondon et al, 2002)
Summary
Status epilepticus (SE) is the first manifestation of epilepsy in approximately 50% of patients (Chapman et al, 2001). The excitatory role of GABA is due to molecular alterations that affect the natural function of GABA in epileptic tissue (Huberfeld et al, 2007) It characterizes the silent phase: epileptogenesis groups together a series of events during which irreversible neuronal lesions appear. The excitation (glutamate + GABA) becomes much too strong and the inhibition much too weak and leads to the establishment of a chronic state characterized by the occurrence of abnormal discharges in the neurons (Cherubini et al, 2011) the recurrence of spontaneous crises (Cavalheiro et al, 2006) These pathophysiological changes lead to the development of comorbidities related to epilepsy. GSH is a cofactor of the ROS detoxification pathways formed, the regulation of the redox potential, and the reduction of oxidation of the thiols groups of the proteins (Sohal and Weindruch, 1996; Beckman and Ames, 1998)
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