Epilepsy is a chronic neurological disorder with significant treatment challenges, necessitating the search for alternative therapies. This study evaluates the anticonvulsant activity and toxicological profile of Verbesina persicifolia leaf extracts. Methanolic and sequential fractions (hexane, dichloromethane, ethyl acetate, and methanol) were tested using a pentylenetetrazole (PTZ)-induced seizure model in zebrafish (Danio rerio), measuring seizure latency, severity, and survival rates. Phytochemical screening confirmed the presence of flavonoids, alkaloids, and steroids, suggesting potential neuroactive properties. The hexane extracts significantly increased seizure latency and survival rates, with co-administration of hexane extract (5 µg/mL) and diazepam (35.5 µM) further enhancing these effects. Toxicity assessment in Artemia salina indicated low to moderate toxicity in methanolic extracts, while sequential fractions exhibited higher toxicity, particularly in hexane and ethyl acetate extracts. These findings suggest that V. persicifolia extracts exert anticonvulsant effects, likely through GABAergic modulation, and exhibit a favorable safety profile at therapeutic doses. The results support further investigations to isolate active constituents, confirm their mechanisms of action, and explore their potential as plant-derived anticonvulsant agents.

Epilepsy remains a widespread neurological disorder, with approximately 30% of patients showing resistance to current antiepileptic therapies. To address this unmet need, a series of 2-(isoindolin-2-yl) esters derived from natural amino acids were designed and evaluated for their potential interaction with the GABA_A receptor. Sixteen derivatives were subjected to in silico assessments, including physicochemical and ADMET profiling, virtual screening–ensemble docking, and enhanced sampling molecular dynamics simulations (metadynamics calculations). Among these, compounds derived from the aromatic amino acids, phenylalanine, tyrosine, tryptophan, and histidine, exhibited superior predicted affinity, attributed to π–π stacking interactions at the benzodiazepine binding site of the GABA_A receptor. Based on computational performance, the tyrosine and tryptophan derivatives were synthesized and further assessed in vivo using the pentylenetetrazole-induced seizure model in zebrafish (Danio rerio). The tryptophan derivative produced comparable behavioral seizure reduction to the reference drug diazepam at the tested concentrations. The results implies that aromatic amino acid-derived isoindoline esters are promising anticonvulsant candidates and support the hypothesis that π–π interactions may play a critical role in modulating GABA_A receptor binding affinity.

Epilepsy is a chronic neurological disorder with significant treatment challenges, necessitating the search for alternative therapies. This study evaluates the anticonvulsant activity and toxicological profile of Verbesina persicifolia leaf extracts. Methanolic and sequential fractions (hexane, dichloromethane, ethyl acetate, and methanol) were tested using a pentylenetetrazole (PTZ)-induced seizure model in zebrafish (Danio rerio), measuring seizure latency, severity, and survival rates. Phytochemical analysis identified flavonoids, alkaloids, and steroids, suggesting neuroactive potential. Ethyl acetate and hexane fractions significantly increased seizure latency and survival rates, with co-administration of hexane extract and diazepam enhancing these effects. Toxicity assessment in Artemia salina indicated low to moderate toxicity in methanolic extracts, whereas sequential fractions exhibited higher toxicity, particularly in hexane and ethyl acetate extracts. Cell viability assays in chicken embryo fibroblasts confirmed a concentration-dependent safety profile. The findings suggest that V. persicifolia extracts exert anticonvulsant effects, likely through GABAergic modulation, and have a favorable safety profile at therapeutic doses. These results support further investigations to isolate active constituents and explore their potential as plant-derived anticonvulsant agents.

La bioética nació como un instrumento primordial que ampara los derechos de los seres vivos y cobija la protección del bienestar animal no solo en el ámbito de investigación, sino como parte del accionar del ser humano. En la actualidad, los modelos animales representan lo más aproximado para estudiar respuestas fisiológicas y patológicas en el humano, además, de probar nuevos compuestos biológicos. En el presente trabajo se comparan los principales modelos animales para la evaluación e investigación de la epilepsia y se reflexionan sus aspectos éticos en estudios realizados por diferentes equipos de investigación en el mundo.

Epilepsy remains a widespread neurological disorder, with approximately 30% of patients showing resistance to current antiepileptic therapies. To address this unmet need, a series of 2-(isoindolin-2-yl) esters derived from natural amino acids were designed and evaluated for their potential interaction with the GABAA receptor. Sixteen derivatives were subjected to in silico assessments, including physicochemical and ADMET profiling, virtual screening - ensemble docking, and enhanced sampling molecular dynamics simulations (metadynamics calculations). Among these, compounds derived from the aromatic amino acids, phenylalanine, tyrosine, tryptophan, and histidine exhibited superior predicted affinity, attributed to π–π stacking interactions at the benzodiazepine binding site of the GABAA receptor. Based on computational performance, the tyrosine and tryptophan derivatives were synthesized and further assessed in vivo using the pentylenetetrazole-induced seizure model in zebrafish (Danio rerio). Both compounds significantly reduced seizure severity, with the tryptophan derivative demonstrating equal efficacy to the reference drug diazepam. The results suggest that aromatic amino acid-derived isoindoline esters are promising anticonvulsant candidates and suggest that π–π interactions play a critical role in modulating GABAA receptor binding affinity.

Justicia spicigera is a central medicinal plant in Mexican ethnomedicine, yet its therapeutic potential against prostate cancer remains largely unexplored. This study investigated the antiproliferative and pro-apoptotic effects of a 50% hydroalcoholic extract from the leaves and stems of J. spicigera on androgen-sensitive LNCaP prostate cancer cells. Phytochemical profiling via TLC and LC-MS putatively identified the bioactive flavonoid kaempferitrin within the complex extract. Biological assays, including MTT, trypan blue exclusion, and flow cytometry, revealed that the extract inhibits LNCaP proliferation in a distinct, dose-dependent manner. At a lower concentration (250 µg/mL), the extract exerted a primarily cytostatic effect by inducing significant G₀/G₁ cell cycle arrest without triggering immediate cell death. Conversely, higher concentrations (≥500 µg/mL) were potently cytotoxic, reducing cell viability to below 20% and inducing late apoptosis in approximately 58% of the population within 24 hours. These results validate the biological activity of J. spicigera in a prostate cancer model and suggest that the extract, or its constituent flavonoids could serve as a template for developing treatments that target both cell cycle checkpoints and programmed cell death.