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).