Chemistry Reference
In-Depth Information
with a decrease in protein and mRNA expression after treatment with ginkgo-
lides.
119,120
Recent studies have shown that the primary action of GB is the inhibi-
tion of PB receptor expression,
121
which is mediated through binding to a
transcription factor, and it has been suggested that GB regulates excess glucocorti-
coid formation, through the PB receptor-controlled steroidogenesis.
122,123
Numerous studies have shown that ginkgolides protect against various CNS inci-
dents, such as ischemia and cerebrovascular and traumatic brain injury, as well as
inflammation
11
; It is not understood how ginkgolides exert this effect, but it has
been suggested that they interference with oxygen free radicals,
124
or reduction
of glutamate-induced neurotoxicity
125,126
could play a role. Moreover, ginkgolides
might reduce cytotoxic nitric oxide.
127
Finally, in vitro studies with ginkgolides
have also shown cardioprotective effects.
124,128,129
7.5
CONCLUSIONS AND OUTLOOK
The intriguing and complex structures of ginkgolides were discovered more than 35
years ago by a dazzling endeavor. Since then, many chemical and biological studies
have been carried out including total syntheses of these complex natural products
and elucidation of a novel, and general, biosynthetic pathway. The finding that
ginkgolides are antagonists of the PAF receptor led to extensive SAR studies pro-
viding important information of the ligand-receptor interaction. Certainly, we will
see even more detailed studies of this interaction in the future, when photoactiva-
table and radiolabeled ginkgolides are employed. The recent finding that ginkgo-
lides are also antagonists of inhibitory ligand-gated ion channels, particularly
glycine receptors, has opened up a new area for SAR studies as well as for detailed
mechanistic studies. Moreover, the physiological implications of this effect, for
example, for people taking G. biloba extract, are not yet known.
ACKNOWLEDGMENT
Dr. Stanislav Jaracz is thanked for providing illustrations to Figures 7-1 and 7-2.
REFERENCES
1. Strømgaard, K.; Nakanishi, K. Chemistry and biology of terpene trilactones from
Ginkgo biloba. Angew. Chem. Int. Ed., 2004, 43: 1640-1658.
2. Major, R. T. The ginkgo, the most ancient living tree. Science, 1967, 157: 1270-1273.
3. Jacobs, B. P.; Browner, W. S. Ginkgo biloba: A living fossil. Am. J. Med., 2000, 108:
341-342.
4. Goethe, J. W. West-Ostlicher Divan. T¨ bingen: Niemeyer, 1819.
5. Drieu, K.; Jaggy, H. History, development, and constituents of EGb 761. In Medicinal
and Aromatic Plants—Industrial Profiles, Vol. 12: Ginkgo biloba. Amsterdam: Harwood
Academic Publishers, 2000, 267-277.
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