Bioactivity guided fractionation of Bombax ceiba L. root extract for antidepressant activity and elucidation of mechanism of action using in silico studies

Abstract

The glutamate system has received considerable attention in recent years as a target for development of novel therapeutics, including antidepressants. There are several lines of evidence showing the role of excitatory glutamatergic neurotransmission in depression and antidepressant activity of N-methyl D-aspartate (NMDA) antagonists like ketamine. The excitoxicity induced by glutamate receptor subtype NMDA is selectively and markedly inhibited by hesperidin. The hesperidin is one of the active constituents isolated from the roots of the cotton tree, Bombax ceiba L. (Bombacaceae). In this context, here, we studied the antidepressant activity of ethanolic extract of root of B. ceiba and its fractions viz., chloroform fraction CBCR (200 & 400 mg/kg); ethyl acetate fraction EABCR (200 & 400 mg/kg); n-butanol fraction (200 & 400 mg/kg) using two animal models of learned helplessness. To further elucidate the possible NMDA antagonist effect of hesperetin, an active metabolite of hesperedin, in silico docking studies were carried out using 5VIH protein of Rattus norvegicus (Brown rat) which consists of GluN1/GluN2A NMDA receptor agonist binding domains, using Inventus v 1.1. Results of in silico study revealed good binding affinity of hesperetin to 5VIH protein. The data indicated antidepressant like activity of the extract and its fractions. The effect was more promising with ethyl acetate and n-butanol fraction of the extract which could be attributed to the antagonistic effect of hesperetin to GluN1/GluN2A NMDA receptor, present in roots of B. ceiba