P-19-17 - Further characterization of effects of dynorphin on galanin-induced amnesia

Abstract

Gugulipid, an ethyl acetate extract of the resin of plant Commiphora whighitii is an established hypolipidemic agent in clinical practice. The major constituent of gugulipid is guggulsterone [4, 17 (20)-pregnadiene-3, 16-dione]. It has been observed recently that patients receiving lipid-lowering drugs like statins have a reduced risk of dementia. Therefore, the present study was planned to explore the potential of gugulipid as cognitive enhancer. Gugulipid (12.5, 25 and 50 mg/kg, p.o.) showed dose dependent improvement in scopolamine-induced deficits in passive avoidance test. The maximal effective dose of gugulipid i.e. 50 mg/kg, p.o. was used for further studies on streptozotocin (STZ) model of dementia in mice. Gugulipid was investigated for its effect on learning and memory, parameters of oxidative stress (GSH and MDA) and acetylcholinesterase (AChE) activity in the STZ (ic)-treated mice. Intracerebral (ic) injections of STZ (0.5 mg/kg) on 1st and 3rd day caused significant deficit in memory in passive avoidance and Morris water maze test after the 14th day of first dose. In passive avoidance, transfer latency time (TLT) was not increased on retention trials in STZ (ic) group while gugulipid treatment resulted in significant increase in TLT on retention trials in STZ (ic)-treated mice. In Morris water maze test the latency time to reach platform in STZ (ic)-treated mice was significantly higher than control and vehicle (artificial CSF). Pre-treatment of gugulipid (50 mg/kg, p.o.) daily for 14 days started with the first dose of STZ (ic), significantly prevented STZ (ic)-induced memory deficit. Post-treatment i.e. after 14 days of first dose of STZ (ic) of gugulipid (50 mg/kg, p.o.) significantly decreased the latency time indicating anti-dementia activity. Effect of gugulipid and STZ in visible platform test was similar to those seen with hidden platform. Gugulipid and STZ-treated mice did not cause significant change in locomotor activity. Furthermore, STZ (ic) resulted into increase in AChE activity, low level of GSH and high concentration of MDA in brain on 21st day as compared to control. Gugulipid treatment caused significant decrease in AChE activity, low level of MDA and high concentration of GSH in brain following STZ (ic) as compared to vehicle administration in STZ (ic)-treated mice. The study demonstrated that gugulipid has significant protective affect against streptozotocin-induced memory deficits model of dementia that can be attributed to anti-oxidant and anti-AChE activity of gugulipid. These observations suggest gugulipid as a potential anti-dementia drug (CDRI, Lucknow has obtained US patent No. 6896901 for use of gugulipid as cognitive enhancer).