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Objective: The present investigation was aimed at discovery of novel acetylcholinesterase (AChE) inhibitors.Methods: In vitro AchE inhibitory activity of various extracts of Sphaeranthus indicus flower heads was carried out. The petroleum ether fraction of S. indicus flowers (SIPE) exhibited significant activity. The fraction was found to be rich in sesquiterpene lactone content possibly responsible for in vitro AChE inhibition. In further study, the antiamnesic activities of SIPE in mice on the learning and memory impairments induced by scopolamine (1.0 mg/kg, i.p.) were examined.Results: SIPE (10 mg/kg, p.o.) administration significantly reversed cognitive impairments in mice by passive avoidance test (P &lt; 0.05). It also reduced escape latencies in training trials and prolonged swimming times in the target quadrant during the probe trial in the water maze task (P &lt; 0.05). These results indicated that S. indicus due to its sesquiterpene lactones have anti-cholinesterase activity. A major sesquiterpene lactone, 7-hydroxy frullanolide along with other constituents were isolated from SIPE and evaluated for AchE inhibitory activity. Negative results were obtained in case of isolated compounds.Conclusion: Synergistic effect between constituents of SIPE was confirmed to have anti-amnesic activities that may be useful for cognitive impairment treatment.

Sphaeranthus indicus Flower Derived Constituents Exhibits Synergistic Effect against Acetylcholinesterase and Possess Potential Antiamnestic Activity