PHARMACOLOGY AND BIOLOGICAL
ACTIVITIES
Ginkgo leaf extract has vascular tone-regulat-
ing properties, an antihypoxic effect, experi-
mental inhibitory activity in cerebral edema,
and neurotoxicity; modulates cerebral energy
metabolism;^10 free radical scavenging prop-
erties;^11 inhibits lipid peroxidation of mem-
branes, helping to maintain integrity and
permeability of cell walls;^12 antiasthmatic,
bronchodilator, and so on. (WREN).
Perhaps the most extensively studied activ-
ity of ginkgo is its antioxidant activity and it is
probably the key to its significant protective
effects. Numerous reports have appeared in
recent literature that link such activity to
neuroprotection,13–19 hepatoprotection,20–23
radioprotection,^21 cancer chemoprevention
and apoptosis,24–29Alzheimer’s disease (am-
yloid-beta protein inhibition),30–32 reduced
cerebral ischemia/stroke,19,33–36 gastropro-
tection (antiulcer),26,37,38nephroprotection,^39
reduced mitochondrial stress,40,41and even
skin disorders (vitiligo).^42
Ginkgo’s inhibitory effect on the produc-
tion of amyloid-beta protein has also been
mediated by other mechanisms, such as
acetylcholinesterase inhibition, modulation of
amyloid protein oligomeric species, and low-
ering of free cholesterol levels.43–45
Numerous pharmacological and clinical
studies of ginkgo leaf extract have demon-
strated a positive effect in increasing vaso-
dilation and peripheral blood flow rate in
capillary vessels and end arteries in various
circulatory disorders, Reynaud’s disease, var-
icose conditions, post-thrombotic syndrome
(WEISS),^46 chronic cerebral vascular insuffi-
ciency,^47 short-term memory improvement,^48
cognitive disorders secondary to depression,
dementia,^49 tinnitus,^50 vertigo, obliterative
arterial disease of the lower limbs,^51 and other
conditions.^46 A retrospective critical review
of the quality and methodology of 40 trials
(published since 1975) on the use of ginkgo
extracts in cerebral insufficiency has found
eight such trials to be of high quality.^52 Vaso-
dilatation and antihypertension have been the
subject of more research supporting earlier
findings. Some of the involved mechanisms
include inhibition of cGMP-phosphodiester-
ase-5, induction of NO release, and Ca^2 þ
channel modulation.4,53–58Behavioral effects
of ginkgo as well as its effects on memory and
cognition have also been under investigation
invarious animal and human trials. Significant
memory and behavioral enhancements were
observed in rats and dogs under different
stressors.59–66Results of recent human trials
further supported earlier results.67–69
Ginkgolide B is a selective antagonist of
platelet aggregation induced by platelet-acti-
vating factor (PAF). PAF, an inflammatory
autacoid, is involved in various inflammatory,
cardiovascular, and respiratory disorders.70–72
Ginkgo extract has also displayed anti-inflam-
matroy activity in a number of conditions and
disease models such as colitis, arthritis, skin
inflammation, and rat paw edema.73–78Anti-
inflammatory mediators have been suppressed
by the extract.73,79
Ginkgo leaf extracts, bilobalide and ginkgo-
lide A, have shown antidepressant/antistress
effects in different animal models, which ap-
pears to be mediated by antagonism of the
GABAreceptorandbyelevatingbraincatecho-
laminesandplasmacorticosteronelevels.3,80–84
Other recently reported activities of ginkgo
include estrogenic/antiestrogenic,85,86immu-
nostimulatory,^87 larvicidal,^88 and modulation
of certain cytochrome enzyme subtypes.89–91
Many reviews about the pharmacology and
therapeutic potential of ginkgo have been
published.32,92–100TOXICOLOGYA number of isolated incidents attributed to
the use of ginkgo have recently appeared in the
literature, including accidental intoxication of
2-year-old male and female,101,102exanthem-
atous pustulosis,^103 spontaneous bleeding,^104
and ventricular arrhythmia.^105USESMedicinal, Pharmaceutical, and Cosmetic.
A standardized extract of the dried leaves is326 Ginkgo