Fatty Acid Amides Synthesized from Andiroba Oil (Carapa guianensis Aublet.) Exhibit Anticonvulsant Action with Modulation on GABA-A Receptor in Mice: A Putative Therapeutic Option

Oliveira, Fábio Rodrigues de; Rodrigues, Keuri Eleutério; Hamoy, Moisés; Sarquis, Ícaro Rodrigues; Hamoy, Akira Otake; Crespo-López, María Elena; Ferreira, Irlon M.; Macchi, Barbarella de Matos; Nascimento, José Luíz Martins do

doi:10.3390/ph13030043

Cited by 10 publications

(5 citation statements)

References 76 publications

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“…administration appears to be insufficient to enhance the activity of the GABAergic system in the background of the impaired GABA A receptor function in PTZ-treated mice. However, a recent report indicates that fatty acid amides, with an affinity for FABPs, show anti-epileptic action in PTZ-treated mice, an effect blocked by flumazenil [ 37 ]. Further studies are necessary to investigate the effect of MF1 on other types of GABA A receptors.…”

Section: Discussionmentioning

confidence: 99%

Anti-Epileptic Effects of FABP3 Ligand MF1 through the Benzodiazepine Recognition Site of the GABAA Receptor

Yabuki

Liu

Kawahata

et al. 2020

IJMS

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Recently, we developed the fatty acid-binding protein 3 (FABP3) ligand MF1 (4-(2-(1-(2-chlorophenyl)-5-phenyl-1H-pyrazol-3-yl)phenoxy) butanoic acid) as a therapeutic candidate for α-synucleinopathies. MF1 shows affinity towards γ-aminobutyric acid type-A (GABAA) receptor, but its effect on the receptor remains unclear. Here, we investigate the pharmacological properties of MF1 on the GABAA receptor overexpressed in Neuro2A cells. While MF1 (1–100 μm) alone failed to evoke GABA currents, MF1 (1 μm) promoted GABA currents during GABA exposure (1 and 10 μm). MF1-promoted GABA currents were blocked by flumazenil (10 μm) treatment, suggesting that MF1 enhances receptor function via the benzodiazepine recognition site. Acute and chronic administration of MF1 (0.1, 0.3 and 1.0 mg/kg, p.o.) significantly attenuated status epilepticus (SE) and the mortality rate in pilocarpine (PILO: 300 mg/kg, i.p.)-treated mice, similar to diazepam (DZP: 5.0 mg/kg, i.p.). The anti-epileptic effects of DZP (5.0 mg/kg, i.p.) and MF1 (0.3 mg/kg, p.o.) were completely abolished by flumazenil (25 mg/kg, i.p.) treatment. Pentylenetetrazol (PTZ: 90 mg/kg, i.p.)-induced seizures in mice were suppressed by DZP (5.0 mg/kg, i.p.), but not MF1. Collectively, this suggests that MF1 is a mild enhancer of the GABAA receptor and exercises anti-epileptic effects through the receptor’s benzodiazepine recognition site in PILO-induced SE models.

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Section: Discussionmentioning

confidence: 99%

Anti-Epileptic Effects of FABP3 Ligand MF1 through the Benzodiazepine Recognition Site of the GABAA Receptor

Yabuki

Liu

Kawahata

et al. 2020

IJMS

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“…For electrode implantation, the animals were anesthetized with an association of Xylazine Hydrochloride (5mg/kg) and Ketamine Hydrochloride (50mg/kg) through intraperitoneal injection, with an initial infiltration of lidocaine (2%) at the surgical incision site. The electrodes were implanted at the Bregma -0.96mm stereotaxic coordinate [26] and ± 1mm lateral to the dura mater region just above the motor cortex [27][28][29][30]. The electrode was in contact with the surface of the dura mater.…”

Section: Surgery For Electrode Placementmentioning

confidence: 99%

Unmasking hidden risks: The surprising link between PDE5 inhibitors and seizure susceptibility

Silva,

Nascimento,

Azevedo

et al. 2023

PLoS ONE

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Background Phosphodiesterase 5 inhibitors (PDE5i) are the first line treatment for erectile dysfunction; however, several articles and case reports have shown central nervous system effects, that can cause seizures in susceptible patients. This study aims to describe the changes caused by the use of Sildenafil and Tadalafil through the analysis of abnormalities expressed in the electrocorticogram (ECoG) of rats and evaluate the seizure threshold response and treatment of seizures with anticonvulsants. Materials and methods The study used 108 rats (Wistar). Before surgery for electrode placement in dura mater, the animals were randomly separated into 3 experiments for electrocorticogram analysis. Experiment 1: ECoG response to using PD5i (Sildenafil 20mg/kg and Tadalafil 2.6mg/kg p.o.). Experiment 2: ECoG response to the use of PD5i in association with Pentylenetetrazole (PTZ—30 mg/kg i.p.), a convulsive model. Experiment 3: ECoG response to anticonvulsant treatment (Phenytoin, Phenobarbital and Diazepam) of seizures induced by association IPDE5 + PTZ. All recordings were made thirty minutes after administration of the medication and analyzed for ten minutes, only once. We considered statistical significance level of *p<0.05, **p<0.01 and ***p < 0.001. Results After administration of Sildenafil and Tadalafil, there were increases in the power of recordings in the frequency bands in oscillations in alpha (p = 0.0920) and beta (p = 0.602) when compared to the control group (p<0.001). After the use of Sildenafil and Tadalafil associated with PTZ, greater potency was observed in the recordings during seizures (p<0.001), however, the Sildenafil group showed greater potency when compared to Tadalafil (p<0.05). Phenobarbital and Diazepam showed a better response in controlling discharges triggered by the association between proconvulsant drugs. Conclusions PDE5i altered the ECoG recordings in the rats’ motor cortexes, demonstrating cerebral asynchrony and potentiating the action of PTZ. These findings demonstrate that PDE5i can lower the seizure threshold.

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“…The medicinal and other technological applications of CWO have been an active area of research [23]. For example, biocatalysis and enzymatic catalysis have been used to transform CWO into materials suitable for biomedical and industrial applications [24,25]. Free fatty acid amides (FFAA) with anticonvulsant properties have been produced using biocatalysts [25].…”

Section: Introductionmentioning

confidence: 99%

“…For example, biocatalysis and enzymatic catalysis have been used to transform CWO into materials suitable for biomedical and industrial applications [24,25]. Free fatty acid amides (FFAA) with anticonvulsant properties have been produced using biocatalysts [25]. CWO has been used for the preparation of biodiesel by enzymatic catalysis [24].…”

Section: Introductionmentioning

confidence: 99%

“…The authors used dry fractionation and with acetone reported yields of 41% for the solid fraction from dry fractionation and 53% for the soluble fraction from acetone. Carapa guianensis, which has approximately 30% total saturated fatty acids compared to 40% for Carapa grandiflora [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36], is expected to provide very different stearin and olein fractions. CWO fractionation, as a means to extend and amplify the use of the oil, is more challenging than the other tropical oils because of its high unsaturation levels.…”

Section: Introductionmentioning

confidence: 99%

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Lipid Fractionation and Physicochemical Characterization of Carapa guianensis Seed Oil from Guyana

James,

Bouzidi,

Emery

et al. 2023

Processes

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The seed oil of Carapa guianensis, known as crabwood oil (CWO), is distinguished for its medicinal and cosmetics applications, attributed to its bioactive components and lipid profile. CWO and its dry and solvent fractionation were studied, with a focus on physicochemical functionality and the partitioning of known bioactive compounds, such as limonoids and sterols. Important bioactive components, including limonoids and sterols, were partitioned depending on the fractionation method; in particular, there is a direct dependence on solvent polarity. There was a very strong solid fraction yield–solvent polarity with a high linear slope of −121.3%. The partitioning of the lipids is significant enough to drive measurable and predictable changes in the physical properties. Palmitic (P: C16:0) and oleic (O: C18:1) fatty acids account for about 60% of the total fatty acid composition of the TAGs of CWO and its fractions. The most abundant limonoid is methyl angolensate (from 28 to 39%), followed by Trichilin A (from 13% to 22%). Gedunin and Andirobin were more abundant in the liquid fractions, whereas Carapanolides (less than 1.3%) were more present in the olein fractions. The crystallization and melting temperatures of the solid fractions were up to 26 °C, compared to 11 °C for CWO, and were particularly strongly correlated to the polarity of the solvents. The SFC profile indicated semi-solid fats, with the solid fractions showing up to 19% at 18 °C, twice the SFC in CWO. The fractions demonstrated a wide range of distinguishable microstructures. The shapes include well-organized spherulites and needle-like and rod-like crystals with sizes varying from 5 to 250 µ, suggesting that they are likely to have different flow characteristics and feel to the skin and mouth. There is a potential to make unique compositions with significantly different properties, with antimicrobial and antifungal efficacy due to the bioactive components of CWO through fractionation, using polarity as a predictive tool.

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Fatty Acid Amides Synthesized from Andiroba Oil (Carapa guianensis Aublet.) Exhibit Anticonvulsant Action with Modulation on GABA-A Receptor in Mice: A Putative Therapeutic Option

Cited by 10 publications

References 76 publications

Anti-Epileptic Effects of FABP3 Ligand MF1 through the Benzodiazepine Recognition Site of the GABAA Receptor

Anti-Epileptic Effects of FABP3 Ligand MF1 through the Benzodiazepine Recognition Site of the GABAA Receptor

Unmasking hidden risks: The surprising link between PDE5 inhibitors and seizure susceptibility

Lipid Fractionation and Physicochemical Characterization of Carapa guianensis Seed Oil from Guyana

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