Anticonvulsant and behavioral effects observed in mice following treatment with an ester derivative of ferulic acid: Isopentyl ferulate

Machado, Keylla C.; Oliveira, George Laylson da Silva; Machado, Kátia Conceição; Islam, Muhammad Torequl; G., Antonio Luiz; Sousa, Damião Pergentino de; Freitas, Rivelilson Mendes de

doi:10.1016/j.cbi.2015.10.003

Cited by 21 publications

(8 citation statements)

References 44 publications

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“…Our ndings demonstrated that nitric oxide pathway (to some extent) mediated the anticonvulsant effect of ferulic acid. To date, a number of empirical studies have shown the anticonvulsant effects of ferulic acid (21,24,25), which are in line with the results of the present study. In the Lin et al study, ferulic acid showed protective effects against glutamate-induced neuronal stimulation and inhibited glutamate release from cortical synaptosomes by inhibiting voltage-dependent calcium channels in the presynaptic membrane (26).…”

Section: Discussionsupporting

confidence: 92%

Implication of Nitrergic System in the Anticonvulsant Effect of Ferulic Acid in Pentylenetetrazole-induced Seizures in Male Mice

Khoei

Boroujeni

Lorigooini

et al. 2020

Preprint

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Background and Aim: Given the widespread prevalence of seizures worldwide and the low efficacy of synthetic drugs, studies are needed to find new compounds with appropriate efficacy. Ferulic acid (FA) is a phenolic compound with antioxidant and neuroprotective effects. The aim of present study was to investigate the role of nitrergic system in the anticonvulsant effect of FA in pentylenetetrazol-induced seizures in male mice. Material and Methods: 64 male NMRI mice weighing 25-29 g were randomly divided into 8 experimental groups (n=8). FA at doses 5, 10 and 40 mg / kg alone and in combination with L-NAME (nitric oxide synthase inhibitor) or L-arg (nitric oxide precursor) was administrated (i.p.). PTZ was injected (i.v. route) 30 min after drugs administration. Seizure onset time was recorded and the nitrite levels of prefrontal cortex and serum were determined by Griess Method. Results: FA at doses of 10 and 40 mg / kg significantly increased the seizure threshold as well as reduced the serum and brain nitric oxide levels in comparison to the saline- received group. Co-administration of effective dose of FA (10 mg/kg) plus L-arginine significantly decreased the seizure threshold in compared to the effective dose of FA alone. Co-injection of sub-effective dose of FA (5 mg/kg) with L-NAME significantly increased the seizure threshold as well as significantly decreased the brain nitric oxide level in compared to the sub-effective dose of FA alone.Conclusion: FA partially at least, via modulation of nitrergic system possessed anticonvulsant effect in PTZ-induced seizures in mice.

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Section: Discussionsupporting

confidence: 92%

Implication of Nitrergic System in the Anticonvulsant Effect of Ferulic Acid in Pentylenetetrazole-induced Seizures in Male Mice

Khoei

Boroujeni

Lorigooini

et al. 2020

Preprint

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“…According to the results found in this work, Machado et al (2015) reported that isopentyl ferulate, a FA ester, also acted on BZD binding site on GABAA receptors by reversing its anticonvulsive effect with flumazenil.…”

Section: Discussionsupporting

confidence: 54%

“…To increase treatment options, it is necessary to search for new molecules with greater therapeutic efficacy than the existing drugs. In that point of view, compounds obtained from plants represent an excellent source for the discovery of new substances with therapeutic potential (Machado et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Anxiolytic activity of ferulic acid in the light-dark test in zebrafish

Sborgi

Fernandes

Santos

et al. 2021

RSD

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The anxiety disorders belong to a group of mental disorders in which the patients present excessive fear and worry. Studies with ferulic acid have shown positive results on treating depressive symptoms. As many antidepressive drugs are effective in treating anxiety, the objective of the present study was to evaluate ferulic acid’s anxiolytic activity and possible mechanism of action in the light-dark test in zebrafish. To evaluate anxiolytic activity, the light-dark preference test was performed after exposure of the animals to ferulic acid or positive control (clonazepam or fluoxetine). Ferulic acid increased the time spent in the clear compartment at concentrations of 250 and 500 mg/L, not differing from the groups exposed to clonazepam or fluoxetine. To evaluate the possible mechanism of action, pre-exposure to flumazenil was carried out, followed by exposure to ferulic acid or positive control, with subsequent testing. Pre-exposure to flumazenil caused a significant reduction in the time spent in the clear compartment of ferulic acid and clonazepam groups but did not alter the effect of exposure to fluoxetine. These results suggest that ferulic acid promotes an anxiolytic effect, possibly through an action at the benzodiazepine binding site at the GABAA receptor.

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“…FA improves cognitive function (Hassanzadeh et al, 2017;Deepa et al, 2012) in response to pent ylenetetrazol (PTZ), a γ-aminobutyric acid type A (GABA(A)) receptor blocker that induces seizure. Its ester, isopentyl ferulate, showed the anti-seizures effect in mice induced by both pilocarpine and pentylenetetrazole, but can be blocked by flumazenil, which suggested the effect may be through the benzodiazepine-binding site of the GABAA (Machado et al, 2015). However, there is no significantly affect locomotor activity and motor coordination.…”

Section: Introductionmentioning

confidence: 99%

Ferulic acid ameliorates pentylenetetrazol-induced seizures by reducing neuron cell death

et al. 2019

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To investigate the neuroprotective effect of ferulic acid (FA) in a pentylenetetrazol (PTZ)induced seizures rat model, the seizures behaviour, spatial learning ability and memory capability of the rats were assessed. Both the antioxidation and anti-apoptosis pathways were also investigated. In this study, male Wistar rats were randomly divided into 3 groups (n = 12 in each group). For 28 days, the rats were administered saline alone (i.p. normal saline, NS group), PTZ (40 mg/kg, i.p., PTZ group) once daily to induce seizures, or FA (i.p. 60 mg/kg) 20 min before being given PTZ (40 mg/kg, i.p., FA + PTZ group) to assess the neuroprotective effect of FA. The seizures behaviour of the rats was analysed with the Racine scale. The spatial learning and memory capacity of the rats were assessed by the Morris water maze test. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were measured, and both in situ staining with the DNA-binding bisbenzimide Hoechst 33258 and TUNEL assays were used to assess apoptosis. Western blotting was used to further analyse the expression of Apaf-1, caspase-9, caspase-3, Bcl-2, Bid, Bax, cleaved caspase-3 and cytochrome c. The results showed that compared to the those of the PTZ group, FA pre-treatment significantly (p < 0.01) reduced the Racine scores starting at day 4, prolonged the latency of the onset of seizure at day 28, reduced the escape latency period starting at day 2, increased the frequency of crossing the platform location, increased the SOD activity, reduced the MDA content and apoptosis rate, and upregulated the Bcl-2 levels whilst downregulating the Bax, cytochrome c, Apaf-1, caspase-9, caspase-3, cleaved caspase-3 and Bid expression levels. This study demonstrated that pre-treatment with FA exerts strong neuroprotective effects by reducing seizures behaviour and by improving spatial learning ability and memory capacity. The neuroprotective effect may be a result of a reduction in neuron cell death that occurs via the antioxidative and anti-apoptotic pathways.

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Anticonvulsant and behavioral effects observed in mice following treatment with an ester derivative of ferulic acid: Isopentyl ferulate

Cited by 21 publications

References 44 publications

Implication of Nitrergic System in the Anticonvulsant Effect of Ferulic Acid in Pentylenetetrazole-induced Seizures in Male Mice

Implication of Nitrergic System in the Anticonvulsant Effect of Ferulic Acid in Pentylenetetrazole-induced Seizures in Male Mice

Anxiolytic activity of ferulic acid in the light-dark test in zebrafish

Ferulic acid ameliorates pentylenetetrazol-induced seizures by reducing neuron cell death

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