Identification of multi-targeting and synergistic neuromodulators of epilepsy associated protein-targets in Ayurvedic herbs using network pharmacological approach

Abstract

Epilepsy comprises a wide spectrum of neuronal disorders and accounts for about one percent of global disease burden affecting people of all age groups. In the traditional medicinal system of Indian antiquity, commonly known as Ayurveda, epilepsy is recognised as apasmara and a plenty of information is documented regarding the effectiveness of various herbs against it. Towards exploring the complex regulatory mechanisms of Ayurvedic herbs at molecular levels, in this study, a network pharmacological framework is developed for thoroughly examining the anti-epileptic potential of 349 drug-like phytochemicals (DPCs) found in 63Ayurvedic herbs. Interaction networks of phytochemicals in anti-epileptic herbs, their protein targets and associated human pathways are designed at various scales and DPCs are mapped on these networks to uncover complex interrelationships. Neuromodulatory prospects of anti-epileptic herbs are probed and, as a special case study, DPCs that can regulate metabotrophic glutamate receptors (mGluRs) are inspected. An account of novel regulatory phytochemicals against epilepsy is reported by systematically analysing the screened DPCs against DrugBank compounds. A repertoire of DPCs having poly-pharmacological similarity with anti-epileptic drugs available in DrugBank and those under clinical trials is also reported. Further, a high-confidence PPI network specific to the protein targets of epilepsy was developed and the potential of DPCs to regulate its functional modules was investigated. The study concludes by highlighting a couple of herbs as potential sources of epileptogenic regulators. We believe that the presented schema can open-up the exhaustive explorations of indigenous herbs towards meticulous identification of DPCs against various diseases and disorders.