Neuropharmacology and AnalgesiaOsthole suppresses seizures in the mouse maximal electroshock seizure model
Introduction
Osthole {[7-methoxy-8-(3-methyl-2-butenyl)-2H-1-benzopyran-2-one], a natural coumarin derivative (Fig. 1)}, is extracted from many medicinal plants, such as Angelica pubescens, Cnidium monnieri and Peucedanum ostruthium (Teng et al., 1994, Chen et al., 2000, Cisowski et al., 2001, Chou et al., 2007). Previous experimental studies have shown that osthole exerts a broad spectrum of pharmacological activities due to its antiproliferative, vasorelaxing, anti-hepatitis, anti-inflammatory, antiaggregatory and anti-allergic effects (Ko et al., 1989, Ko et al., 1992, Huang et al., 1996, Liu et al., 1998, Chiou et al., 2001, Matsuda et al., 2002, Yang et al., 2003).
Accumulating evidence indicates that imperatorin {[9-(3-methylbut-2-enyloxy)-7H-furo[3,2-g]chromen-7-one], a natural furanocoumarin derivative (Fig. 1)} possesses the anticonvulsant activity in preclinical studies by elevating the threshold for electroconvulsions (Luszczki et al., 2007a) and enhancing the antielectroshock action of carbamazepine, phenobarbital, phenytoin (Luszczki et al., 2007b), and lamotrigine (Luszczki et al., 2008) in mice.
Since osthole and imperatorin (two naturally occurring coumarin derivatives) have similar chemical structures (Fig. 1), we expected that osthole would also exert the anticonvulsant action in mice. Therefore, we examined the dose–response relationship and time course of action of osthole against maximal electroshock-induced seizures in mice. Generally, the maximal electroshock-induced seizure test in rodents is considered as a valid experimental model to detect the anticonvulsant action of drugs against generalized tonic–clonic seizures and partial convulsions with or without secondary generalization in humans (Fisher, 1989, Löscher et al., 1991). Moreover, this experimental model of epilepsy is widely used for an investigation of the new drugs and for preselection of the agents with antiseizure activity in vivo (Fisher, 1989, Löscher et al., 1991).
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Materials and methods
Adult male Swiss mice (weighing 22–26 g) that were kept in colony cages (20 per cage) with free access to food and tap water, under standardized housing conditions (12 h light–dark cycle, temperature of 23 ± 1°C, relative humidity of 55 ± 5%), were used. After 7 days of adaptation to laboratory conditions, the animals were randomly assigned to experimental groups comprising of 8 mice. Each mouse was used only once and all tests were performed between 08:00 a.m. and 03:00 p.m. Procedures involving
Results
Osthole administered systemically (i.p.), at 15, 30, 60 and 120 min before the test, produced a clear-cut anticonvulsant activity in the mouse maximal electroshock-induced seizure test and the experimentally-derived ED50 values for the natural coumarin derivative were 266, 259, 443, and 631 mg/kg, respectively (Fig. 2). Considering dose–response relationship and time course of anticonvulsant action of osthole in the maximal electroshock-induced seizure test and comparing the ED50 values for
Discussion
Results indicate that osthole administered systemically (i.p.), at various pretreatment times (15, 30, 60 and 120 min) before the maximal electroshock-induced seizure test, produced a clear-cut antielectroshock action in mice. The maximum anticonvulsant activity of osthole (at 15 and 30 min after its i.p. administration) was similar to that as documented earlier for imperatorin (Luszczki et al., 2007a). Moreover, the systemic (i.p.) administration of osthole, at various pretreatment times and
Disclosure of conflicts of interest
The authors have no conflicts of interest to disclose.
Acknowledgement
This study was supported by a grant from the Medical University of Lublin (Lublin, Poland). The authors express their thanks to Miss K. Tejchman for her technical assistance.
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2020, Chemico-Biological InteractionsCitation Excerpt :Accumulated evidence demonstrates that Chinese herbal agents provide a new hope for effective cancer treatments [18] and some agents show promise in the treatment of HNSCC [19,20]. Osthole, an active ingredient of Cnidium monnieri (L.), has been widely applied as an anti-allergic, anti-osteoporotic, anti-inflammatory, and anti-seizure agent [8–10,12]. Recent literature suggests that osthole exerts anticancer effects by inhibiting cell growth through induced cell cycle arrest and apoptosis [21,22].