MEDICINAL CHEMISTRY OF GINKGOLIDES FROM GINKGO BILOBA - Medicinal Chemistry of Bioactive Natural Products - page 303

the leaves also inspired German poet, scientist, botanist, and philosopher Johann
Wolfgang von Goethe (1749-1832), to write a poem called ''Gin(k)go biloba,''
which is dedicated to his former lover Marianne von Willemer. 4
The earliest records on the use of G. biloba as medicine dates back to 1505 AD , 5
where G. biloba treated aging members of the royal court for senility. Around 1965,
leaf preparations of G. biloba were introduced to the Western world by Dr. Willmar
Schwabe, 5 and together with Beaufour-Ipsen (now Ipsen), a standardized G. biloba
extract called EGb 761 was developed. 6 Many G. biloba products have entered the
market, and G. biloba extract is now among the best-selling herbal medications
worldwide. G. biloba was originally grown throughout China and Korea, but it
was introduced to Europe and North America in the eighteenth century. Today
over 50 million G. biloba trees are grown, particularly in China, France, and South
Carolina in the United States, producing approximately 8000 tons of dried leaves
each year. 7
EGb 761 is standardized with respect to the content of terpene trilactones
(6%) and flavonoids (24%). 5 The terpene trilactones are the five ginkgolides and
bilobalide, whereas the flavonoids are mainly flavonol-O-glycosides. EGb 761
contains many other components, including proanthocyanidins (prodelphinidins)
and organic acids, particularly ginkgolic acids (anarcardic acids), which have
allergenic properties; hence, the content in EGb 761 is limited to 5 ppm. 5 In studies
of the pharmacological effects of G. biloba, particularly on effects in the central
nervous system (CNS), EGb 761 has been widely used, 8-12 and the effects
include improvement of cognition, antioxidant effects, increased cerebral blood
flow and circulation, modification of neurotransmission, and protection against
apoptosis. 11
The most extensive clinical studies with EGb 761 have focused on alleviation of
Alzheimer's disease (AD). 13-15 Two studies with a total of 549 AD patients showed
that treatment with EGb 761 significantly slowed the loss of cognitive symptoms of
dementia. 16,17 However, two recent clinical studies with more then 400 patients
have cast doubt on the positive clinical effect of EGb 761. 18,19 Several meta-
analyses have reviewed over 50 clinical studies using EGb 761 for treatment of
dementia and cognitive functions associated with AD, and these studies conclude
that EGb 761 have a small but significant effect on objective measures of cognitive
function in AD, without significant adverse effects. 20 Currently, at least two major
clinical trials are ongoing. The U.S. National Institutes of Health is sponsoring the
Ginkgo evaluation of memory (GEM) study, which has enrolled more than 3000
older people recruited from four medical centers in the United States. In France,
the pharmaceutical company Ipsen is sponsoring another clinical trial, the GuidAge
study, which examines prevention of AD in patients over the age of 70 with
memory impairment. The results from these two studies will obviously be of major
importance in evaluating and determining the effects of GBE in relation to
dementia. Therefore, EGb 761 might be beneficial in relieving symptoms of AD,
although the reported effects are often small. However, in light of the current
lack of treatment for AD patients, 21,22 EGb 761 could prove useful as an alternative
to the currently available treatments.