Vitexin Possesses Anticonvulsant and Anxiolytic-Like Effects in Murine Animal Models

Abstract

Different types of epilepsy and forms of pathological anxiety have been described as significant neurological disorders that may exist as comorbidities. Some of those disorders share the association of affected limbic areas/neuropathological triggers as well as the use of drugs for their clinical management. The aim of this work was to investigate the anticonvulsant and anxiolytic properties of the vitexin (apigenin-8-Cglucoside), since this compound is a flavonoid usually found as one of the major constituents in several medicinal plants claimed as anxiolytics and/or anticonvulsants. This investigation was performed by the use of a series of classical murine animal models of chemically induced-seizures and of anxiety-related tests (open-field, elevated plusmaze, and light-dark box tests). Here, we show that the systemic administration of vitexin (1.25; 2.5 and 5 mg/kg; i.p.) exhibited selective protection against chemically-induced seizures. Vitexin did not block seizures evoked by glutamate receptors agonists (NMDA and kainic acid), and it did not interfere with the latencies for these seizures. Conversely, the same treatments protected the animals in a dose-dependent manner against the seizures evoked by the Gabaergic antagonists picrotoxin and PTZ and rise the latency time for the first seizure on non-protected animals. The higher dose of vitexin protected 100% of animals against the tonic-clonic seizures triggered by GABA antagonists. The results from open-field, elevated plus-maze, and light-dark box tests indicated the anxiolytic properties of vitexin at similar range of doses described for the anticonvulsant action screening. Furthermore, these results pointed that vitexin did not cause sedation or locomotor impairment on animals. The selective action of vitexin against picrotoxin and PTZ may reinforce the hypothesis by which this compound acts mainly by the modulation of GABAergic neurotransmission and/or related pathways. This could be useful to explain the dual activity of vitexin as anticonvulsant and anxiolytic, and highlight the pharmacological interest on this promising flavonoid.

The Genus Alternanthera: Phytochemical and Ethnopharmacological Perspectives

“…Various mechanisms elucidated by them are like modulation of GABAergic system, controlling the entry of calcium and sodium ions in the cells, and glycine regulation in spinal cord ( Oyemitan et al, 2015 ). Phytomolecules like vitexin ( de Oliveira et al, 2020 ), quercetin ( Nassiri-Asl et al, 2014 ; Nieoczym et al, 2014 ), stigmasterol ( Karim et al, 2021 ), chlorogenic acid ( Aseervatham et al, 2016 ), and ferulic acid ( Hassanzadeh et al, 2017 ) may be responsible for the antiepileptic effect of Alternanthera brasiliana (L.) Kuntze.…”

“…Results were quite significant ( Mondal et al, 2014 ). Phytoconstituents acting on GABA receptors like Ricinoleic acid ( Witt et al, 2002 ), Chlorogenic acid ( Hara et al, 2014 ), p-Coumaric acid ( Scheepens et al, 2014 ), Ferulic acid ( Cheng et al, 2010 ; Sonar et al, 2019 ), Ellagic acid ( Girish et al, 2013 ), Spinasterol ( Socała et al, 2015 ), Stigmasterol ( Karim et al, 2021 ), Acacetin analogs ( Gálvez et al, 2015 ), Vitexin and vitexin analogs ( Zhu et al, 2016 ; de Oliveira et al, 2020 ), and Quercetin and quercetin analogs ( Goutman and Calvo, 2004 ; Kim et al, 2014 ) which were previously been reported from Alternanthera sessilis (L.) R.Br. ex DC., may be behind this GABA receptor mediated central-stimulating activity.…”

Drought-Mediated Modulation in Metabolomic Profiling of Leaf, Growth, Ecophysiology and Antioxidants

“…Vitexin and its compounds have been shown to attenuate myocardial ischemia, anticonvulsant and anxiolytic, neuroprotective and many other therapeutic properties [46][47][48][49]. Derivatives and complexes of Quercetin exhibit strong antioxidant activities [50].…”

Human Metabolism and Excretion of Kawakawa (Piper excelsum) Leaf Chemicals

“…[10,11] Vitexin, an apigenin flavone glucoside, is a key component of several edible and medicinal plants such as pearl millet and chasteberry. [12] It has been reported to exhibit antioxidant, anticonvulsant, antiinflammatory activity, and to regulate neuroinflammation [13,14] and have antidiabetic properties. [15] The lignans yangambin and epiyangambin are found in medicinal plants of several families including the Lauraceae [16] and Asteraceae.…”