Influence of xanthotoxin (8-methoxypsoralen) on the anticonvulsant activity of various novel antiepileptic drugs against maximal electroshock-induced seizures in mice

Zagaja, Mirosław; Andres-Mach, Marta; Patrzylas, Paweł; Pyrka, Daniel; Szpringer, Monika; Florek-Łuszczki, Magdalena; Żółkowska, Dorota; Skalicka-Woźniak, Krystyna; Łuszczki, Jarogniew J.

doi:10.1016/j.fitote.2016.09.020

Cited by 28 publications

(34 citation statements)

References 40 publications

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“…Similar research was carried out by the same team to assess the effect of xanthotoxin on the new-generation drugs lacosamide (LCM), pregabalin (PGB), topiramate (TP), oxcarbazepine (OXC) and lamotrigine (LTG) (Zagaja et al, 2016). As in the previous study, the protective activity of the drugs was determined based on the median effective doses (ED 50 values in mg/kg) correlated to the maximum convulsions caused by electroconvulsion.…”

Section: Xanthotoxinmentioning

confidence: 98%

“…Due to its simple structure, it is used as a parent compound in the synthesis of various coumarins and heterocyclic compounds (Mazimba et al, 2017). Subramaniam and Ellis (2013) identified a neuroprotective effect for umbelliferone, where this couma- Zagaja et al, 2016 Results are presented as median effective doses (ED50 in mg/kg; with 95% confidence limits in parentheses) required to protect 50% of animals tested against maximal electroshock-induced seizures. Bolded ED50 values corresponds to the significantly reduced effective dose of combination in comparison to the AED itself.…”

Section: Umbelliferonementioning

confidence: 99%

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Coumarins as potential supportive medication for the treatment of epilepsy

Bryda¹,

Zagaja²,

Szewczyk³

et al. 2019

Acta Neurobiologiae Experimentalis

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Epilepsy, one of the most common neurological disorders, is a chronic disease of the brain manifested by seizures due to sudden, spontaneous bioelectrical discharges in nerve cells. An estimated 50 million people worldwide suffer from epilepsy.Antiepileptic drugs are the mainstream treatment for epilepsy; however, the drug resistance occurring in 20-30% of patients and side effects of available medications have resulted in a search for natural remedies that can support disease therapy. Coumarins may be a promising option. They are a group of natural plant-derived substances of great interest due to their broad spectrum of biological activities, including potent pharmacological properties. Recent data from experimental models demonstrates the possibility for coumarin use as a supporting treatment of epileptic seizures. This article focuses on the most recent research reports available in the literature relating to the use of several selected coumarins in different experimental models of epilepsy.

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Section: Xanthotoxinmentioning

confidence: 98%

Section: Umbelliferonementioning

confidence: 99%

Coumarins as potential supportive medication for the treatment of epilepsy

Bryda¹,

Zagaja²,

Szewczyk³

et al. 2019

Acta Neurobiologiae Experimentalis

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“…The time before the commencement of the grip strength test (after drug administration) was identical to that of the PTZ test. This experimental procedure has been described in detail in our earlier studies [26,32].…”

Section: Grip Strength Testmentioning

confidence: 99%

“…To assess potential acute adverse effects of AS-1, VPA, and their combination (at the fixed ratio 1:1 from the PTZ test) on the mice's ability to acquire the task (learning) and to recall the task (retrieval), the passive avoidance test was used as described in detail in our previous study [26,32]. ) 2 ).…”

Section: Passive Avoidance Taskmentioning

confidence: 99%

N-Benzyl-(2,5-dioxopyrrolidin-1-yl)propanamide (AS-1) with Hybrid Structure as a Candidate for a Broad-Spectrum Antiepileptic Drug

et al. 2020

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In our recent studies, we identified compound N-benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide (AS-1) as a broad-spectrum hybrid anticonvulsant which showed potent protection across the most important animal acute seizure models such as the maximal electroshock (MES) test, the subcutaneous pentylenetetrazole (s.c. PTZ) test, and the 6-Hz (32 mA) test in mice. Therefore, AS-1 may be recognized as a candidate for new anticonvulsant effective in different types of human epilepsy with a favorable safety margin profile determined in the rotarod test in mice. In the aim of further pharmacological evaluation of AS-1, in the current study, we examined its activity in the 6-Hz (44 mA) test, which is known as the model of drug-resistant epilepsy. Furthermore, we determined also the antiseizure activity in the kindling model of epilepsy induced by repeated injection of pentylenetetrazole (PTZ) in mice. As a result, AS-1 revealed relatively potent protection in the 6-Hz (44 mA) test, as well as delayed the progression of kindling induced by repeated injection of PTZ in mice at doses of 15 mg/kg, 30 mg/kg, and 60 mg/kg. Importantly, the isobolographic analysis showed that a combination of AS-1 and valproic acid (VPA) at the fixed ratio of 1:1 displayed a supra-additive (synergistic) interaction against PTZinduced seizures in mice. Thus, AS-1 may be potentially used in an add-on therapy with VPA. Moreover, incubation of zebrafish larvae with AS-1 substantially decreased the number, cumulative but not the mean duration of epileptiform-like events in electroencephalographic assay. Finally, the in vitro ADME-Tox studies revealed that AS-1 is characterized by a very good permeability in the parallel artificial membrane permeability assay test, excellent metabolic stability on human liver microsomes (HLMs), no significant influence on CYP3A4/CYP2D6 activity, and moderate inhibition of CYP2C9 in a concentration of 10 μM, as well as no hepatotoxic properties in HepG2 cells (concentration of 10 μM).

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“…Besides, XAT can also induce apoptosis of tumor cells ( 10 , 11 ). It was demonstrated that XAT had anticonvulsant pharmacological effects in the maximal electroshock-induced seizure test ( 12 ). However, the effect of XAT on chondrocyte differentiation remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Hypertrophic differentiation of mesenchymal stem cells is suppressed by xanthotoxin via the p38-MAPK/HDAC4 pathway

Cao

Bai

Liu

et al. 2017

Molecular Medicine Reports

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Chondrocyte hypertrophy is a physiological process in endochondral ossification. However, the hypertrophic-like alterations of chondrocytes at the articular surface may result in osteoarthritis (OA). In addition, the generation of fibrocartilage with a decreased biological function in tissue engineered cartilage, has been attributed to chondrocyte hypertrophy. Therefore, suppressing chondrocyte hypertrophy in OA and the associated regeneration of non-active cartilage is of primary concern. The present study examined the effects of xanthotoxin (XAT), which is classified as a furanocoumarin, on chondrocyte hypertrophic differentiation of mesenchymal stem cells. Following XAT treatment, the expression levels of genes associated with chondrocyte hypertrophy were detected via immunohistochemistry, western blotting and reverse transcription-quantitative polymerase chain reaction. The results revealed that XAT inhibited the expression of various chondrocyte hypertrophic markers, including runt related transcription factor 2 (Runx2), matrix metalloproteinase 13 and collagen type X α1 chain. Further exploration indicated that XAT reduced the activation of p38-mitogen activated protein kinase and then increased the expression of histone deacetylase 4 to suppress Runx2. The findings indicated that XAT maintained the chondrocyte phenotype in regenerated cartilage and therefore may exhibit promise as a potential drug for the treatment of OA in the future.

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Influence of xanthotoxin (8-methoxypsoralen) on the anticonvulsant activity of various novel antiepileptic drugs against maximal electroshock-induced seizures in mice

Cited by 28 publications

References 40 publications

Coumarins as potential supportive medication for the treatment of epilepsy

Coumarins as potential supportive medication for the treatment of epilepsy

N-Benzyl-(2,5-dioxopyrrolidin-1-yl)propanamide (AS-1) with Hybrid Structure as a Candidate for a Broad-Spectrum Antiepileptic Drug

Hypertrophic differentiation of mesenchymal stem cells is suppressed by xanthotoxin via the p38-MAPK/HDAC4 pathway

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