Effect of Ginkgo biloba (EGb 761®) on Differential Gene Expression

Supplementation of diets with plant extracts such as ginkgo biloba extract (EGb 761®) (definition see editorial) for health and prevention of degenerative diseases is popular. However, it is often difficult to analyse the biological activities of plant extracts due to their complex nature and the possible synergistic and/or antagonistic effects of their components. Genome-wide expression monitoring with high-density oligonucleotide arrays provides one way to examine the molecular targets of plant extracts and may prove a useful tool in evaluating their therapeutic claims. Here, we will briefly describe some of our work on the effect of EGb 761® on differential gene expression in relation to its potential anti-carcinogenic, photoprotective and neuromodulatory properties.

References

• 1 Ader P, Wessmann A, Wolffram S. Bioavailability and metabolism of the flavonol quercetin in the pig.  Free Radic Biol Med. 2000;  28 1056-1067
• 2 Brusselbach S, Nettelbeck D M, Sedlacek H H, Muller R. Cell cycle-independent induction of apoptosis by the anti-tumor drug Flavopiridol in endothelial cells.  Int J Cancer. 1998;  77 146-152
• 3 Elson C E, Peffley D M, Hentosh P, Mo H. Isoprenoid-mediated inhibition of mevalonate synthesis: potential application to cancer.  Proc Soc Exp Biol Med. 1999;  221 294-311
• 4 Gohil K, Moy R K, Farzin S, Maguire J J, Packer L. mRNA expression profile of a human cancer cell line in response to Ginkgo biloba extract: induction of antioxidant response and the Golgi system.  Free Radic Res. 2000;  33 831-849
• 5 Gong C X, Lidsky T, Wegiel J, Zuck L, Grundke-Iqbal I, Iqbal K. Phosphorylation of microtubule-associated protein tau is regulated by protein phosphatase 2A in mammalian brain. Implications for neurofibrillary degeneration in Alzheimer's disease.  J Biol Chem. 2000;  275 5535-5544
• 6 Iqbal K, Alonso A C, Gong C X, Khatoon S, Pei J J, Wang J Z, Grundke-Iqbal I. Mechanisms of neurofibrillary degeneration and the formation of neurofibrillary tangles.  J Neural Transm Suppl. 1998;  53 169-180
• 7 Irani K, Xia Y, Zweier J L, Sollott S J, Der C J, Fearon E R, Sundaresan M, Finkel T, Goldschmidt-Clermont P J. Mitogenic signaling mediated by oxidants in Ras-transformed fibroblasts.  Science. 1997;  275 1649-1652
• 8 Keogh B P, Allen R G, Pignolo R, Horton J, Tresini M, Cristofalo V J. Expression of hydrogen peroxide and glutathione metabolizing enzymes in human skin fibroblasts derived from donors of different ages.  J Cell Physiol. 1996;  167 512-522
• 9 Le Bars P L, Katz M M, Berman N, Itil T M, Freedman A M, Schatzberg A F. A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. North American EGb Study Group.  JAMA. 1997;  278 1327-1332
• 10 Lee P J, Alam J, Wiegand G W, Choi A M. Overexpression of haem oxygenase-1 in human pulmonary epithelial cells results in cell growth arrest and increased resistance to hyperoxia.  Proc Natl Acad Sci U S A. 1996;  93 10 393-10 398
• 11 Meister A. Glutathione deficiency produced by inhibition of its synthesis, and its reversal; applications in research and therapy.  Pharmacol Therap. 1991;  51 155-194
• 12 Nyberg F. Growth hormone in the brain: characteristics of specific brain targets for the hormone and their functional significance.  Front Neuroendocrinol. 2000;  21 330-348
• 13 Porterfield S P. Thyroidal dysfunction and environmental chemicals-potential impact on brain development.  Environ Health Perspect. 2000;  108 Suppl 3 433-438
• 14 Rimbach G, Gohil K, Matsugo S, Moini H, Saliou C, Virgili F, Weber S U, Packer L. Induction of glutathione synthesis in human keratinocytes by Ginkgo biloba extract (EGb761).  Biofactors. 2001;  15 39-52
• 15 Rimbach G, Saliou C, Canali R, Virgili F. Interaction between cultured endothelial cells and macrophages: in vitro model for studying flavonoids in redox-dependent gene expression.  Methods Enzymol. 2001;  335 238-242
• 16 Saliou C, Valacchi G, Rimbach G. Assessing bioflavonoids as regulators of NF-kB acitivity and gene expression in mammalian cells.  Methods Enzymol. 2001;  335 380-387
• 17 StClair D K, Oberley L W. Manganese superoxide dismutase expression in human cancer cells: a possible role of mRNA processing.  Free Radic Res Commun. 1991;  12 - 13 Pt 2 771-778
• 18 Steenvoorden D P, Hasselbaink D M, Beijersbergen van Henegouwen G M. Protection against UV-induced reactive intermediates in human cells and mouse skin by glutathione precursors: a comparison of N-acetylcysteine and glutathione ethylester.  Photochem Photobiol. 1998;  67 651-656
• 19 Tsuzuki K, Fukatsu R, Yamaguchi H, Tateno M, Imai K, Fujii N, Yamauchi T. Transthyretin binds amyloid beta peptides, Abeta1 - 42 and Abeta1 - 40 to form complex in the autopsied human kidney - possible role of transthyretin for abeta sequestration.  Neurosci Lett. 2000;  281 171-174
• 20 Tyrrell R M, Pidoux M. Correlation between endogenous glutathione content and sensitivity of cultured human skin cells to radiation at defined wavelengths in the solar ultraviolet range.  Photochem Photobiol. 1988;  47 405-412
• 21 Watanabe C M, Wolffram S, Ader P, Rimbach G, Packer L, Maguire J J, Schultz P G, Gohil K. The in vivo neuromodulatory effects of the herbal medicine ginkgo biloba.  Proc Natl Acad Sci U S A. 2001;  98 6577-6580
• 22 Yoshikawa T, Naito Y, Kondo M. Ginkgo biloba leaf extract: Review of biological actions and clinical applications.  Antioxidant Redox Signal. 1999;  1 469-480
• 23 Zi X, Agarwal R. Silibinin decreases prostate-specific antigen with cell growth inhibition via G1 arrest, leading to differentiation of prostate carcinoma cells: implications for prostate cancer intervention.  Proc Natl Acad Sci U S A. 1999;  96 7490-7495