Terpene trilactones from Gingko biloba: from ancient times to the 21st century.

Ginkgolides were always close to my heart. I continue to be strongly attracted to Ginkgo biloba, the ginkgolides and bilobalide. Starting in 1963, I became fascinated by these molecules while working on their isolation and structure elucidation in Sendai. Presumably, due to the ginkgolide studies, I received an invitation to join the faculty at Columbia University. After almost three decades of not touching the ginkgolide project, we have unexpectedly resumed the studies, at this time because of their enigmatic biological effects. This account is a reflection on earlier studies, as well as an outline of our current work.

[1]  K. Nakanishi,et al.  Ginkgolides: selective acetylations, translactonization, and biological evaluation. , 2002, The Journal of organic chemistry.

[2]  A. Schatzberg,et al.  A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. North American EGb Study Group. , 1997, JAMA.

[3]  A. Wieraszko,et al.  Platelet activating factor (PAF) in memory formation: role as a retrograde messenger in long-term potentiation. , 1996, Journal of lipid mediators and cell signalling.

[4]  J. Buccafusco,et al.  Multiple central nervous system targets for eliciting beneficial effects on memory and cognition. , 2000, The Journal of pharmacology and experimental therapeutics.

[5]  Kunio Kato,et al.  Platelet-activating factor as a potential retrograde messenger in CA1 hippocampal long-term potentiation , 1994, Nature.

[6]  O. Krishtal,et al.  Inhibition of hippocampal LTP by ginkgolide B is mediated by its blocking action on PAF rather than glycine receptors , 2004, Neurochemistry International.

[7]  G. Toubin,et al.  The effect of ginkgo biloba extract on free radical production in hypoxic rats. , 2001, Biological & pharmaceutical bulletin.

[8]  K. Nakanishi,et al.  Structure of bilobalide, a rare tert-butyl containing sesquiterpenoid related to the C20-ginkgolides , 1971 .

[9]  R. C. Mehrotra,et al.  Reaction of silicon tetrachloride with tertiary butyl acetate. A novel synthesis of silicon tetraacetate , 1963 .

[10]  K. Nakanishi,et al.  The ginkgolides. II Derivation of partial structures , 1967 .

[11]  K. Weinges,et al.  Chemie der Ginkgolide, II. Isolierung und Strukturaufklärung eines neuen Ginkgolids , 1987 .

[12]  S. Matsuda,et al.  Cloning and characterization of Ginkgo biloba levopimaradiene synthase which catalyzes the first committed step in ginkgolide biosynthesis. , 2001, Archives of biochemistry and biophysics.

[13]  K. Kato Modulation of long-term potentiation in the CA1 area of rat hippocampus by platelet-activating factor. , 1999, Advances in experimental medicine and biology.

[14]  T. Itil,et al.  Natural substances in psychiatry (Ginkgo biloba in dementia). , 1995, Psychopharmacology bulletin.

[15]  T. Manabe,et al.  Platelet‐activating factor receptor is not required for long‐term potentiation in the hippocampal CA1 region , 1999, The European journal of neuroscience.

[16]  A. Kriegstein,et al.  Terpene Trilactones from Ginkgo biloba Are Antagonists of Cortical Glycine and GABAA Receptors* , 2003, Journal of Biological Chemistry.

[17]  K. Nakanishi,et al.  Preparation of 7-substituted ginkgolide derivatives: potent platelet activating factor (PAF) receptor antagonists. , 2003, Journal of medicinal chemistry.

[18]  E. Rüther,et al.  Prescribing practice with cognition enhancers in outpatient care: are there differences regarding type of dementia?--Results of a representative survey in lower Saxony, Germany. , 2007, Pharmacopsychiatry.

[19]  D. Kennedy,et al.  The dose-dependent cognitive effects of acute administration of Ginkgo biloba to healthy young volunteers , 2000, Psychopharmacology.

[20]  中西 香爾,et al.  Comprehensive natural products chemistry , 1999 .

[21]  P. D. Tredici THE EVOLUTION, ECOLOGY, AND CULTIVATION OF GINKGO BILOBA , 2000 .

[22]  K. Nakanishi,et al.  Ginkgolides and glycine receptors: a structure-activity relationship study. , 2004, Chemistry.

[23]  Katsunori Tanaka,et al.  Preparation of ginkgolide and F-seco-ginkgolide lactols: the unique reactivity of α-hydroxy lactones toward NaBH4 , 2005 .

[24]  S. Ishii,et al.  Platelet-activating factor (PAF) receptor and genetically engineered PAF receptor mutant mice. , 2000, Progress in lipid research.

[25]  P. Schultz,et al.  The in vivo neuromodulatory effects of the herbal medicine ginkgo biloba , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[26]  K. Nakanishi,et al.  Biosynthesis of ginkgolide B, its diterpenoid nature, and origin of the tert-butyl group , 1971 .

[27]  Paul F. Smith,et al.  PLATELET-ACTIVATING FACTOR IN THE CNS , 1996, Progress in Neurobiology.

[28]  Turan M. Itil,et al.  A Placebo-Controlled, Double-blind, Randomized Trial of an Extract of Ginkgo Biloba for Dementia , 1997 .

[29]  A. Ogura,et al.  Platelet-activating factor (PAF) receptor in rat brain: PAF mobilizes intracellular Ca2+ in hippocampal neurons , 1992, Neuron.

[30]  P. Houghton,et al.  MEDICINAL AND AROMATIC PLANTS INDUSTRIAL PROFILE , 1996 .

[31]  S. Chatterjee,et al.  Phospholipid breakdown and choline release under hypoxic conditions: inhibition by bilobalide, a constituent of Ginkgo biloba , 1997, Brain Research.

[32]  J. V. Smith,et al.  Studies on molecular mechanisms of Ginkgo biloba extract , 2004, Applied Microbiology and Biotechnology.

[33]  T. V. van Beek,et al.  Quantitation of bilobalide and ginkgolides A, B, C and J by means of nuclear magnetic resonance spectroscopy. , 1993 .

[34]  K. Nakanishi,et al.  Chemistry and biology of terpene trilactones from Ginkgo biloba. , 2004, Angewandte Chemie.

[35]  J. Polich,et al.  Cognitive effects of a Ginkgo biloba/vinpocetine compound in normal adults: systematic assessment of perception, attention and memory , 2001, Human psychopharmacology.

[36]  J. Doucet,et al.  Excitable membranes, lipid messengers, and immediate-early genes , 2007, Molecular Neurobiology.

[37]  J. Magee,et al.  Attenuated LTP in hippocampal dentate gyrus neurons of mice deficient in the PAF receptor. , 2001, Journal of neurophysiology.

[38]  F. Mahmoud,et al.  In vitro effects of Ginkgolide B on lymphocyte activation in atopic asthma: comparison with cyclosporin A. , 2000, Japanese journal of pharmacology.

[39]  D. Warburton Ginkgo biloba extract and cognitive decline. , 1993, British journal of clinical pharmacology.

[40]  K. Drieu,et al.  Decreased cerebral 5‐HT1A receptors during ageing: reversal by Ginkgo biloba extract (EGb 761) , 1994, The Journal of pharmacy and pharmacology.

[41]  K. Nakanishi,et al.  Ginkgolide derivatives for photolabeling studies: preparation and pharmacological evaluation. , 2002, Journal of medicinal chemistry.

[42]  K. Nakanishi,et al.  The ginkgolides. III. The structure of the ginkgolides , 1967 .

[43]  K. Nakanishi,et al.  The ginkgolides. V. Some aspects of their NMR spectra , 1967 .

[44]  K. Nakanishi,et al.  Efficient extraction of ginkgolides and bilobalide from Ginkgo biloba leaves. , 2002, Journal of natural products.

[45]  N. Bazan,et al.  Platelet-activating factor in the modulation of excitatory amino acid neurotransmitter release and of gene expression. , 1996, Journal of lipid mediators and cell signalling.

[46]  F. V. Defeudis,et al.  Ginkgo biloba extract (EGb 761) and CNS functions: basic studies and clinical applications. , 2000, Current drug targets.

[47]  K. Nakanishi,et al.  The ginkgolides. I. Isolation and characterization of the various groups , 1967 .

[48]  James B. Thomas,et al.  Total Synthesis of (.+‐.)‐Ginkgolide B. , 2010 .

[49]  F. Huguet,et al.  α2‐Adrenoceptor Changes During Cerebral Ageing. The Effect of Ginkgo biloba Extract , 1992, The Journal of pharmacy and pharmacology.

[50]  Cytotoxicity of alkylphenols from Ginkgo biloba. , 1999, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[51]  C. Benezra,et al.  Allergic contact dermatitis to Ginkgo biloba L.: relationship with urushiol , 2004, Archives of Dermatological Research.

[52]  Arun K. Ghosh,et al.  Total Synthesis of (±)-Ginkgolide B. , 1988, Journal of the American Chemical Society.

[53]  I. Hindmarch,et al.  The effects of acute doses of standardized Ginkgo biloba extract on memory and psychomotor performance in volunteers , 1999, Phytotherapy research : PTR.