Ginkgo biloba may have neuroprotective effects in

stroke in mice
Susan Jeffrey
May 08, 2000
Mon, 08 May 2000 15:00:18
San Diego, CA - Oregon researchers are investigating whether ginkgo biloba, a daily supplement
widely used for memory enhancement, may offer beneficial effects in the setting of ischemic stroke.
While translation of positive results seen with neuroprotective agents in animal models into humans
has been notoriously difficult, they are reporting pretreatment with ginkgo reduced infarct sizes by
35% in mice. Their paper was presented here at the 52nd Annual Meeting of the American
Academy of Neurology.
Ginkgo is extracted from the nuts and fan-shaped leaves of the gingko biloba tree, and has been
used medicinally for centuries in Asia. More recently, it has been shown clinically to produce
memory improvement in patients with Alzheimer's symptoms, said Dr Wayne Clark (Director,
Oregon Stroke Center, Oregon Health Sciences University), lead author of the report. As a result, it
is widely used in the healthy population for purposes of memory enhancement, particularly by the
elderly, he said.
Ginkgo contains a variety of pharmacologically active compounds, some of which could be beneficial
in stroke, including "very strong free-radical scavenging, and an effect of blocking platelet adhesion,"
Clark told heart wire in an interview. It also blocks activation and adhesion of leukocytes and
increases cerebral blood flow.
To begin investigating this potential benefit, the researchers pretreated adult mice with 2 doses of
ginkgo - 50 mg/kg/day (low-dose) or 100 mg/kg/day (high-dose) - or placebo for 1 week. They used
a commercial preparation from Germany, where levels of pharmacologically active compounds in the
extract are regulated, unlike many preparations in the US. They then compared infarct sizes and
functional outcomes after inducing an event comparable to a middle cerebral artery stroke in
humans.
The low-dose regimen reduced infarct sizes by approximately 35%, a statistically significant
difference from placebo. The high dose produced no significant reduction in the infarct size, but did
increase the occurrence of significant intracerebral hemorrhage in those animals.
Results of low-dose (50 mg/kg/day) versus high-dose (100 mg/kg/day) ginkgo biloba versus
placebo in adult mice


Indicators and Factors Low-dose
gingko
High-dose
gingko
Placebo
Number of mice
18 22 20
Infarct volume at 24 hours
(mm3)
13+5* 22+12 20+10*
Significant ICH within infarct
0 10% 0
Neurologic function (28-point
behavioral scale)
11.8+1.5 11.4+1.7 11.3+1.8
(NS)
*p=0.02 placebo versus low-dose ginkgo
No differences were seen between groups in neurologic function, which was measured in the mice
using a 28-point behavioral scale.

"If you're on Coumadin, you should probably not take ginkgo
because it does look like it has its own antiplatelet effect."

While much more work will have to be done to define its utility, Clark said, "some things to think
about right now in terms of patients - including heart patients who are taking ginkgo - is that if you're
on Coumadin, you should probably not take ginkgo because it does look like it has its own
antiplatelet effect."
Going forward, they hope to better define the issue of dosing, and, "then see if we can get the NIH
interested in some funding," he added.
Clinical studies using a number of neuroprotectant agents that were promising in animal studies
have recently had disappointing results, dealing something of a blow to the quest for neuroprotection
after stroke. The advantage of ginkgo is that it has already been shown to have some positive
activity in humans, Clark said.
"I guess the one thing that this might have going for it, is it has shown some benefit in the memory
problems, and after stroke, that certainly is a common complaint," he said. "So even if it didn't
decrease the infarct size, it might help the memory after a stroke."
The animals were pretreated, he added, and while the hope is that ginkgo will also have some effect
after the stroke, ginkgo pretreatment may have a role before procedures known to carry neurologic
risk such as cardiac or carotid surgery.