Anticonvulsant Potential and Toxicological Profile of Verbesina persicifolia Leaf Extracts: Evaluation in Zebrafish Seizure and Artemia salina Toxicity Models

Abstract

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.

Keywords: Artemia salina toxicity; GABAergic modulation; PTZ-induced seizures; Verbesina persicifolia; alkaloids; anticonvulsant activity; diazepam synergy; flavonoids; zebrafish epilepsy model.

Figure 1

Latency metrics for zebrafish treated with Verbesina persicifolia extracts obtained by the partition method. (A) No significant differences; (B) (* p ≤ 0.01); (C) (* p = 0.03). Data are presented as medians ± interquartile ranges. The analysis was performed using ANOVA followed by Tukey HSD.

Figure 2

Latency metrics for zebrafish treated with Verbesina persicifolia extracts obtained by the sequential method. (A) Speed Index Latency, (B) Whirlpool Latency, (C) Posture Loss Latency. (B) (* p = < 0.01); (C) (* p = < 0.01). Data are presented as medians +- interquartile ranges. The analysis was performed using ANOVA followed by Tukey HSD.

Figure 3

Latency metrics for zebrafish treated with Verbesina persicifolia hexane extract in combination with pharmacological controls. (A) Speed Index Latency, (B) Whirlpool Latency, and (C) Posture Loss. The administration of sodium valproate and the hexanic partition was at a concentration of 200 µM and 10 µg/mL, respectively. The administration of diazepam and the hexanic partition was at a concentration of 37.5 µM and 5 µg/mL, respectively. (B) (* p = < 0.01); (C) (* p = 0.01), (** p = < 0.01). Data are presented as medians ± interquartile ranges. For A, the analysis was performed using ANOVA followed by Tukey HSD, while for B and C, Kruskal–Wallis was used, followed by the Bonferroni correction for the Mann–Whitney U test.

Figure 4

Survival rates (%) of Verbesina persicifolia extracts in zebrafish under different extraction methods. (A) Partition method: survival rates for hexane, dichloromethane, ethyl acetate, methanol, and water extracts across concentrations (1, 10, 100, and 1000 µg/mL). (B) Sequential method: survival rates for the same solvents across concentrations (0.1, 1, 10, 100, and 1000 µg/mL).