Integrative Network Pharmacology Approach for the Rational Design of a Polyhedral Anticonvulsant Therapy

Abstract

Epilepsy, affecting 50 million people worldwide, involves recurrent seizures due to abnormal brain activity. Since existing antiepileptic drugs may be insufficient, exploring alternative therapies is crucial. This study investigated the anticonvulsant effect of traditionally exploited plants namely; Vacha, Gulvel, Brahmi, Heeng, Jatamansi, Gotu Kola, and Sendha Namak. The herbs were extracted using water and ethanol and screened for phytoconstituents. Various extract compositions were formulated and assessed using the mouse model for acute toxicity and anticonvulsant activity. The most potent combination was identified and further analyzed through network pharmacology to explore its underlying mechanisms. The phytochemical study showed the presence of saponins, flavonoids, alkaloids, and tannins are responsible for therapeutic benefits. Pharmacological evaluations, including acute toxicity studies and seizure phase analysis, revealed that specific herbal combinations were safe at a dose of 2000mg/kg body weight and significantly reduced seizure intensity and mortality rates compared to the control group. Network pharmacology analysis further identified key target proteins (HTR1B, DRD2, CYP2D6, GLRA1, and NR3C1) involved in seizure modulation, reinforcing the role of serotonergic, dopaminergic, and adrenergic systems in epilepsy pathogenesis. This article highlights the anticonvulsant potential of selected herbal extracts, encouraging further research into their mechanisms and clinical applications for epilepsy treatment.