Borneol and Their Impact on the Anticonvulsant Potency
Numerous botanical drugs containing coumarins and terpenes are used in ethnomedicine all over the world for their various therapeutic properties, especially those affecting the CNS system. The treatment of epilepsy is based on antiseizure medications (ASMs), although novel strategies using naturally occurring substances with confirmed antiseizure properties are being developed nowadays. The aim of this study was to determine the anticonvulsant profiles of scoparone (a simple coumarin) and borneol (a bicyclic monoterpenoid) when administered separately and in combination, as well as their impact on the antiseizure effects of four classic ASMs (carbamazepine, phenytoin, phenobarbital and valproate) in the mouse model of maximal electroshock-induced (MES) tonic-clonic seizures. MES-induced seizures were evoked in mice receiving the respective doses of the tested natural compounds and classic ASMs (when applied alone or in combinations). Interactions for two-drug and three-drug mixtures were assessed by means of isobolographic transformation of data. Polygonograms were used to illustrate the types of interactions occurring among drugs. The total brain content of ASMs was measured in mice receiving the respective drug treatments with fluorescent polarization immunoassay. Scoparone and borneol, when administered alone, exerted anticonvulsant properties in the mouse MES model. The two-drug mixtures of scoparone with valproate, borneol with phenobarbital and borneol with valproate produced synergistic interactions in the mouse MES model, while the remaining tested two-drug mixtures produced additivity. The three-drug mixtures of scoparone + borneol with valproate and phenobarbital produced synergistic interactions in the mouse MES model. Verification of total brain concentrations of valproate and phenobarbital revealed that borneol elevated the total brain concentrations of both ASMs, while scoparone did not affect the brain content of these ASMs in mice. The synergistic interaction of scoparone with valproate observed in the mouse MES model is pharmacodynamic in nature. Borneol elevated the brain concentrations of the tested ASMs, contributing to the pharmacokinetic nature of the observed synergistic interactions with valproate and phenobarbital in the mouse MES model.Get more news about 2 borneol,you can vist our website!
1. Introduction
Epilepsy is a chronic neurological disorder characterized by recurrent epileptic seizures. This condition is the fourth most common neurological disorder and affects approx. 1% of the world’s population, 80% of whom live in low- and middle-income countries [1]. To treat this disease, patients with epilepsy use antiseizure medications (ASMs) and may benefit from other therapies such as brain surgery or neuromodulation [2]. Despite these possibilities, a third of patients with epilepsy suffer from pharmacoresistance and side effects. There is, therefore, an urgent need for new, effective and affordable treatments to manage epilepsy [3].
Herbs used in traditional medicine remain the first-line treatment for most people with little or no access to ASMs [1,4]. The study of antiseizure effects of these plants using innovative in vivo assays and the identification of their bioactive principles are key aspects of providing pharmacological evidence for their use. This may also guide research on the discovery of compounds with original bioactivity profiles to solve some of the problems associated with current ASMs [5,6].
Numerous botanical drugs containing furanocoumarins are used in ethnomedicine all over the world for their stomachic, spasmolytic and sedative effects [7,8]. Previously, it has been documented that various naturally occurring coumarins exerted anticonvulsant properties in the mouse maximal electroshock-induced seizure (MES) model and potentiated the anticonvulsant potencies of classic ASMs. Of note, the MES test in rodents reflects tonic-clonic seizures and, to a certain extent, partial convulsions with or without secondary generalization in humans [9]. This seizure model is widely used in preclinical testing of substances with anticonvulsant properties [9]. Experimental studies revealed that imperatorin and osthole (two naturally occurring coumarins) produced anticonvulsant effects by themselves in the mouse MES model in time- and dose-dependent manners [10]. Additionally, the anticonvulsant screen test revealed that xanthotoxin, but not bergapten or oxypeucedanin, exerted anticonvulsant effects in the mouse MES model [11]. It has been found that coumarins potentiate the anticonvulsant effects of classic ASMs. More specifically, umbelliferone significantly potentiated the anticonvulsant action of phenobarbital (PB) and valproate (VPA) but not that of phenytoin (PHT) and carbamazepine (CBZ) in the mouse MES model [12]. Imperatorin potentiated the antiseizure potencies of CBZ, PHT and PB but not that of VPA [13]. Xanthotoxin enhanced the anticonvulsant action of CBZ and VPA but not that of PHT and PB in the mouse MES model [14]. In contrast, osthole had no significant impact on the antiseizure potencies of CBZ, PHT, PB and VPA in experimental animals subjected to MES-induced seizures [15,16]. Of note, the anticonvulsant effects of ASMs in the mouse MES model are usually expressed as the median effective doses (ED50—i.e., doses of the ASMs that protected 50% of the tested animals against tonic-clonic seizures). The mentioned coumarins potentiated the antiseizure activity of some classic ASMs when combined together by reducing their ED50 values. In other words, coumarins potentiated the anticonvulsant potency of some selected ASMs and less drug doses were needed to produce the same effect, i.e., a 50% protection from tonic-clonic seizures in the mouse MES model. Thus, a significant reduction in the ED50 values for ASMs observed after coumarin administration, as compared to the ASMs when administered alone, testifies the potentiation of the antiseizure effects by the coadministered coumarins.
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