Neuropharmacological Exploration of Standardized Extract of Annona squamosa (L.) Fruit Pulp in Experimental Animals

Abstract

Aims: The present study aimed to investigate the neuroprotective potential of standardized Annona squamosa Linn fruit pulp extract using various in-vitro and in-vivo models. Methodology: Neuroprotective potential of standardized extract was screened against dopamine-induced contraction of isolated rat vas deferens, serotonin-induced contractions of isolated rat fundus, acetylcholine-induced contractions of isolated goat tracheal chain. In-vivo models such as elevated plus maze, light and dark model, force swim test, tail suspension test, lithium-induced head twitches, haloperidol-induced catalepsy, PTZ induced seizure and foot shock-induced aggression were implemented to screen various doses intervals (50-200mg/kg) of extracts in experimental animals. Results: Standardization of extract showed content of polyphenols 65.37 mg/g of GAE, total flavonoid 5.33 mg/g of RE and HPLC fingerprinting of ASP-ME showed identical retention time as that of standard gallic acid, quercetine and rutin, viz 3.830, 5.765 and 3.830 respectively. Inhibition of DPPH radical reflected as 91.32±0.19 % while percent inhibition of RRI of DPPH was observed as 95.99±0.47 at 150 min. ASP-ME significantly inhibited dopamine and serotonin induced contraction on isolated rat vas deferens and rat fundus respectively at log dose (1.3, 2.5) for dopamine and log dose (2.2, 2.5) for serotonin. ASP-ME potentiated ach-induced contractions on goat tracheal chain preparation. Ach alone produces 106.90±4.6 % response, while ASP-ME in presence of Ach potentiates response and produces 141.80±10 % response. The extract demonstrated anxiolytic activity by increasing the time spent in open arms and light zone in elevated plus maze and light dark test respectively. The duration of immobility was significantly decreased in force swim & tail suspension test respectively demonstrating antidepressant activity. Administration of ASP-ME shown antipsychotic effect in dose dependent manner by minimising aggression induced by foot shock (reduced number of flights), while potentiation of catalepsy induced by haloperidol. The extract also exhibited serotonergic system inhibitory effect by significantly reducing head twitches imparted by lithium. The ASP-ME significantly delayed the onset of first myoclonic and clonic spasms induced by PTZ indicating anticonvulsant effects. Extract also shown ability to decrease the behavior facilitated by the serotonergic and dopaminergic coordination, while potentiated the actions produced by GABA. Conclusion: Finding of the study suggests anxiolytic, antidepressant, antipsychotic effects of ASP-ME probably mediated through dopamine D2 and 5-HT receptors, with neuroprotective activity.