Anti-seizure effects of medicinal plants in Malawi on pentylenetetrazole-induced seizures in zebrafish larvae

Medicinal plants are used to manage and treat epilepsy in Malawi because of traditional beliefs and barriers to conventional anti-seizure drugs. Among the plants prescribed by traditional medical practitioners are Margaritaria discoidea, Dalbergia boehmii, Dalbergia nitidula, Catunaregam spinosa, and Lannea discolor. Despite the wide use of these plants, there is a lack of scientific evidence to support their anti-seizure efficacy.This study used the pentylenetetrazole (PTZ)-induced larval zebrafish seizure model to screen for anti-seizure effects of a collection of medicinal plants traditionally used in Malawi.Zebrafish larvae were incubated in decoctions at maximum tolerated concentrations for 18 h and exposed to PTZ. As a primary screen, the effects of the decoctions on seizure-induced locomotor activity were determined. Decoctions that significantly reduced total distance traveled were further checked for effects on seizure latency and frequency, brain activity, immediate early gene expression, and c-fos protein expression.M. discoidea male leaves, D. boehmii roots, and D. nitidula leaves showed significant anti-seizure effects in the primary screen and were selected for further study. Electrophysiological and immediate early gene analyses corroborated anti-seizure effect of D. boehmii and D. nitidula. The results of c-fos protein expression further suggested that the anti-seizure effects in the larval brain may be mediated by the suppression of neurons localized in midbrain regions.These findings provide pioneering scientific evidence of the presence of anti-seizure activity in M. discoidea, D. boehmii, and D. nitidula, prescribed by traditional Malawian medical practitioners. Further studies are needed to identify and isolate compounds responsible for such biological activities and elucidate the possible mechanisms of action.