Zebrafish as a tool for the discovery of anticonvulsant compounds from botanical constituents

Bertoncello, Kanandra Taisa; Bonan, Carla Denise

doi:10.1016/j.ejphar.2021.174342

Cited by 13 publications

(13 citation statements)

References 101 publications

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“…The PTZ-induced model of tonic-clonic seizures in zebrafish is commonly used for initial screening of potential natural 49 − 51 and synthetic anticonvulsant agents. 29 , 52 Larval zebrafish, when incubated in PTZ solution, experience seizures that behaviorally manifested as a hyperactivity.…”

Section: Resultsmentioning

confidence: 99%

“…The PTZ-induced model of tonic-clonic seizures in zebrafish is commonly used for initial screening of potential natural − and synthetic anticonvulsant agents. , Larval zebrafish, when incubated in PTZ solution, experience seizures that behaviorally manifested as a hyperactivity. , Recently, however, it was revealed that relying on the locomotor changes when assessing antiseizure activity of compounds may give false positive results . Therefore, final confirmation should be done using electroencephalographic (EEG) assay.…”

Section: Resultsmentioning

confidence: 99%

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Discovery of (R)-N-Benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide [(R)-AS-1], a Novel Orally Bioavailable EAAT2 Modulator with Drug-like Properties and Potent Antiseizure Activity In Vivo

et al. 2022

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( R )-7 [ ( R )-AS-1 ] showed broad-spectrum antiseizure activity across in vivo mouse seizure models: maximal electroshock (MES), 6 Hz (32/44 mA), acute pentylenetetrazol (PTZ), and PTZ-kindling. A remarkable separation between antiseizure activity and CNS-related adverse effects was also observed. In vitro studies with primary glia cultures and COS-7 cells expressing the glutamate transporter EAAT2 showed enhancement of glutamate uptake, revealing a stereoselective positive allosteric modulator (PAM) effect, further supported by molecular docking simulations. ( R )-7 [ ( R )-AS-1 ] was not active in EAAT1 and EAAT3 assays and did not show significant off-target activity, including interactions with targets reported for marketed antiseizure drugs, indicative of a novel and unprecedented mechanism of action. Both in vivo pharmacokinetic and in vitro absorption, distribution, metabolism, excretion, toxicity (ADME-Tox) profiles confirmed the favorable drug-like potential of the compound. Thus, ( R )-7 [ ( R )-AS-1 ] may be considered as the first-in-class small-molecule PAM of EAAT2 with potential for further preclinical and clinical development in epilepsy and possibly other CNS disorders.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Discovery of (R)-N-Benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide [(R)-AS-1], a Novel Orally Bioavailable EAAT2 Modulator with Drug-like Properties and Potent Antiseizure Activity In Vivo

et al. 2022

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“…Jin used the Zeblab (Viewpoint, Lyon, France) tracking system to analyze the behavior of zebra sh induced by PTZ and evaluate the antiseizure activity of Gastrodin 20 . Even though behavioral assessment of zebra sh allowed direct and rapid identi cation of seizure responses, the special swirly swimming characteristic still could not been quantitative 21,22 . In addition, these commercial tracking system were very high in price.…”

Section: Discussionmentioning

confidence: 99%

Establishment of innovative ZebVortrack behavioral analysis system for quantitative epileptic seizure assessment in larval zebrafish

Chen

Cheng

Jia

et al. 2023

Preprint

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Pro-convulsant agents can cause a series of pathologic swimming behaviors in zebrafish, of which rapid “whirlpool-like” swimming is a representative seizure characteristic behavior. However, there is a lack of good and accurate method to quantify this type of swimming feature. Therefore, in this study, we attempted to establish a new larval zebrafish seizure analysis technique for quantitatively exporting the number of swirly swimming in a certain period. The MARGO software package based on MATLAB was employed to track the zebrafish swimming route and to produce the space–time coordinates. An innovative algorithm was developed based on the factors of vector angle, trajectory length, and swimming duration. Through the optimization of the algorithm, ZebVortrack, an analysis system, was established for automatically recognizing seizure-like swimming behaviors in larval zebrafish, treated with pentylenetetrazol (PTZ). Different pro-convulsant agents, and antiseizure drugs were used to evaluate the accuracy of the ZebVortrack system for larval zebrafish. In a word, we developed a new behavior-analysis system, ZebVortrack, for quantitatively identifying the swirly swimming behavior of larval zebrafish that can automatically and accurately determine the vortex numbers and seizure latency of larval zebrafish in microplate wells so as to provide a new analysis method for study of seizures and drug screening.

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“…were recognized for their versatility to assess the anticonvulsant activities of synthesized compounds or plant extracts [ 146 , 147 ]. Of which, the zebrafish larvae were the most frequently used seizure model because of its high fertility rate and development, similar CNS organization with mammals which can be observed in translucent egg and embryo make it ideal to study CNS disorders provoked by external stimuli [ 148 ]. PTZ, KA, PLC and electrical stimulation are employed to induce convulsions in in the aforesaid non-mammalian seizure models [ 147 ].…”

Section: Pharmacological Evidence Of Reported Medicinal Plantsmentioning

confidence: 99%

Medicinal plants utilized in the management of epilepsy in Ethiopia: ethnobotany, pharmacology and phytochemistry

Birhan

2022

Chin Med

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Epilepsy is a common central nervous system (CNS) disorder that affects 50 million people worldwide. Patients with status epilepticus (SE) suffer from devastating comorbidities and a high incidence of mortalities. Antiepileptic drugs (AEDs) are the mainstream treatment options for the symptomatic relief of epilepsy. The incidence of refractory epilepsy and the dose-dependent neurotoxicity of AEDs such as fatigue, cognitive impairment, dizziness, attention-deficit behavior, and other side effects are the major bottlenecks in epilepsy treatment. In low- and middle-income countries (LMICs), epilepsy patients failed to adhere to the AEDs regimens and consider other options such as complementary and alternative medicines (CAMs) to relieve pain due to status epilepticus (SE). Plant-based CAMs are widely employed for the treatment of epilepsy across the globe including Ethiopia. The current review documented around 96 plant species (PS) that are often used for the treatment of epilepsy in Ethiopia. It also described the in vivo anticonvulsant activities and toxicity profiles of the antiepileptic medicinal plants (MPs). Moreover, the phytochemical constituents of MPs with profound anticonvulsant effects were also assessed. The result reiterated that a lot has to be done to show the association between herbal-based epilepsy treatment and in vivo pharmacological activities of MPs regarding their mechanism of action (MOA), toxicity profiles, and bioactive constituents so that they can advance into the clinics and serve as a treatment option for epilepsy.

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Zebrafish as a tool for the discovery of anticonvulsant compounds from botanical constituents

Cited by 13 publications

References 101 publications

Discovery of (R)-N-Benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide [(R)-AS-1], a Novel Orally Bioavailable EAAT2 Modulator with Drug-like Properties and Potent Antiseizure Activity In Vivo

Discovery of (R)-N-Benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide [(R)-AS-1], a Novel Orally Bioavailable EAAT2 Modulator with Drug-like Properties and Potent Antiseizure Activity In Vivo

Establishment of innovative ZebVortrack behavioral analysis system for quantitative epileptic seizure assessment in larval zebrafish

Medicinal plants utilized in the management of epilepsy in Ethiopia: ethnobotany, pharmacology and phytochemistry

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