Integrated in vivo and in silico assessment of Rauvolfia vomitoria extract on NMDA receptors in a PTZ-induced seizure model

Abstract

Rauvolfia vomitoria (RV) is recognised for its anti-seizure properties, largely due to its rich alkaloid content. In this study, we evaluated the effect of an aqueous extract of Rauvolfia vomitoria on PTZ-induced seizures in male Wistar rats and used in-silico methods to identify the most promising alkaloid compound for predictive analysis. Male Wistar rats (average weight: 160 g) were divided into four groups (n = 5): saline (control), 25 mg/kg PTZ i.p., 200 mg/kg oral RV pretreatment + 25 mg/kg PTZ i.p., and 40 mg/kg oral carbamazepine pretreatment + 25 mg/kg PTZ i.p. Following treatment, we assessed behaviour via the novel object recognition test (NORT) and evaluated antioxidant enzyme levels, brain electrolyte concentrations, and histomorphology changes. Additionally, we employed molecular docking and pharmacokinetic profiling to assess the drug-like properties of the compounds. NORT results revealed increased exploratory time and a non-significant discrimination index. Antioxidant defences were enhanced, while lipid peroxidation indices showed a non-significant reduction. Major electrolyte concentrations were preserved. Molecular docking identified serpentinine as a high-affinity NMDA receptor ligand, with several other Rauvolfia vomitoria alkaloids exhibiting favourable drug-like properties. Oral pretreatment with Rauvolfia vomitoria mitigates PTZ-induced seizure, potentially through antioxidant modulation and a slight trend towards recognition memory. In-silico analyses highlight Rauvolfia vomitoria alkaloids as promising candidates for further experimental validation.