Abstract
As part of our research on phytochemicals that exert protective effects against diseases related to reactive nitrogen specie, we have evaluated the scavenging activity of the yellow leaves ofGinkgo biloba on ONOO−. The methanol extract and ethyl acetate fraction obtained from yellow leaves ofG. biloba evidenced a marked scavenging activity on authentic, ONOO−. Repeated column chromatography of the active ethyl acetate soluble fraction on silica gel, Sephadex LH-20, and RP-18, resulted in the purification of 15 known compounds, including sciadopitysin (1), ginkgolide B (2), bilobalide (3), isoginkgetin (4), kaempferol (5), luteolin (6), protocatechuic acid (7), bilobetin (8), amentoflavone (9), β-sitosterol glucopyranoside (10), kaempferol 3-O-rhamnopyranoside (11), kaempferol 3-O-glucopyranoside (12), kaempferol 3-O-[6‴-O-p-coumaroyl-β-D-glucopyranosyl(1→2)-α-L-rhamnopyranoside] (13), kaempferol 3-O-rutinoside (14), and 6-hydroxykynurenic acid (15). Among the compounds isolated, flavonoids (5, 6 and11–14), protocatechuic acid (7), and 6-hydroxykynurenic acid (15) all exhibited marked scavenging activities on authentic ONOO−. The IC50 values of5–7, 11–14 and 15 were as follows: 2.86±0.70, 2.30±0.04, 2.85±0.10, 5.60±0.47, 4.16±1.65, 2.47±0.15, 3.02±0.48, and 6.24±0.27 μM respectively. DL-Penicillamine (IC50=4.98±0.27 μM) was utilized as a positive control. However, the other compounds (1–4, 8–10) exerted no effects against ONOO−.
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References
Beckman, J. S., Oxidative damage and tyrosine nitration form peroxynitrite.Chem. Res. Toxicol., 9, 836–844 (1996).
Beckman, J. S., Beckman, T. W., Chen, J., Marshall, P. A., and Freeman, B. A., Apparent hydroxyl radical production by peroxynitrite: Implications for endothelial injury form nitric oxide and superoxide.Proc. Nat. Acad. Sci., 87, 1620–1624 (1990).
Beckman, J. S. and Crow, J. P., Pathological implications of nitric oxide, superoxide and peroxynitrite formation.Biochem. Soc. Trans., 21, 330–334 (1993).
Chang, S. K., Youm, J. R., and Kang, S. S., Seasonal variations of biflavone content fromGinkgo biloba leaves.Kor. J. Pharmacogn. 24, 54–57 (1993).
Cheung, F., Siow, Y. L., and Karmin, O., Inhibition by ginkgolides and bilobalide of the production of nitric oxide in macrophages (THP-1) but not in endothelial cells (HUVEC).Biochemical Pharmacology, 61, 503–510 (2001).
Chung, H. Y., Yokozawa, T., Soung, D. Y., Kye, I. S. No, J. K., and Baek, B. S., Peroxynitrite-scavenging activity of green tea tannin.J. Agric. Food Chem., 46, 4484–4486 (1998).
Darley-Usmar, V. and Halliwell, B., Blood radicals: reactive nitrogen species, reactive oxygen species, transition metal ions, and the vascular system.Pharm. Res., 13, 649–662 (1996).
Deliconstantinos, G., Villiotou, V., Stavrides, J. C., Salemes, N., and Gogas, J., Nitric oxide and peroxynitrite production by human erythrocytes: a causative factor of toxic anemia in breast cancer patients.Anticancer Res., 15, 1435–1446 (1995).
Diamond, B. J., Schiflett, S. C., Feiwel, N., Matheis, R. J., Noskin, O., Richards, J. A., and Schoenberger, N. E.,Ginkgo biloba extract: mechanism and clinical indicationsArch. Phys. Med. Rehabil., 81, 668–678 (2000).
Ellnain-Wojtaszek, M., Kruczyñski, Z., and Kasprzak, J., Investigation of the free radical scavenging activity ofGinkgo biloba L. leaves.Fitoterapia, 74, 1–6 (2003).
Gardes-Albert, M., Ferradini, C., Sekaki, A., and Droy-Lefaix, M. T., Oxygen-centered free radicals and their interactions with EGb761 or CP202. In: Ferradini, C., Droy-Lefaix, M. T., and Christen, Y. (Eds.), Advances inGinkgo biloba extract research, Elsevier, Paris, pp. 1–11 (1993).
Good, P. F., Hsu, A., Werner, P., Perl, D. P., and Olanow, C. W., Protein nitration in Parkinson's disease.J. Neuropathol. Exp. Neurol., 57, 338–342 (1998).
Hyun, S. K., Kang, S. S., Son, K. H., Chung, H. Y., and Choi, J. S., Biflavone glucosides fromGinkgo biloba yellow leaves.Chem. Pharm. Bull., 53, 1200–1201 (2005).
Jung, H. A., Kim, J. E., Chung, H. Y., and Choi, J. S., Antioxidant principles ofNelumbo nucifera stamens.Arch. Pharm. Res., 26, 279–285 (2003).
Jung, M. J., Chung, H. Y., and Choi, J. S., Antioxidant activity of roasted defatted Perilla seed.Natural Product Sciences, 7, 72–75 (2001).
Kang, S. G., Youm, J. R., and Kang, S. S., Seasonal variations of the flavonol glycoside content fromGinkgo biloba leaves.Kor. J. Pharmacogn., 24, 47–53 (1993).
Kang, S. S., Koh, Y. M., Kim, J. S., Lee, M. W., and Lee, D. S., Phytochemical analysis ofGinkgo biloba yellow leaves.Kor. J. Pharmacogn., 26, 23–26 (1995).
Kang, S. S., Kim, J. S., Kwak, W. J., and Kim, K. H., Flavonoids from the leaves ofGinkgo biloba.Kor. J. Pharmacogn., 21, 111–120 (1990).
Kerry, N. and Rice-Evans, C. A., Inhibition of peroxynitrite-mediated oxidation of dopamine by flavonoid and phenolic antioxidants and their structural relationship.J. Neurochem., 73, 247–253 (1999).
Kim, A. R., Zou, Y. N., Park, T. H., Shim, K. H., Kim, M. S., Kim, N. D., Kim, J. D., Bae, S. J., Kim, J. D., Bae, S. J., Choi, J. S., and Chung, H. Y., Active components fromArtemisia iwayomogi displaying ONOO− scavenging activity.Phytotherapy Research, 18, 1–7 (2004).
Kim, J. E., Kim, A. R., Chung, H. Y., Han, S. Y., Kim, B. S., and Choi, J. S.,In vitro peroxynitrite scavenging activity of diarylheptanoids fromCurcuma longa.Phytotherapy Research, 17, 481–484 (2003).
Kooy, N. W., Royall, J. A., Ischiropoulos, H., and Beckman, J. S., Peroxynitrite-mediated oxidation of dihydrorhodamine 123.Free Radical Biol. Med., 16, 149–156, (1994).
Maitra, I., Marcocci, L., Packer, L., and Droy-Lefaix, M. T., Peroxyl radical activity ofGinkgo biloba extract EGb761.Biochemical Pharmacology, 49, 1649–1665 (1995).
Mar, C. and Bent, S., An evidence-based review of the 10 most commonly used herbs.West. J. Med., 171, 168–171 (1999).
Marcocci, L., Maguire, J. J., Packer, L., and Droy-Lefaix, M. T., The nitric oxide-scavenging properties ofGinkgo biloba extract EGb761.Biochem. Biophy. Res. Commun., 201, 748–755 (1994).
Marcocci, L., Packer, L., Droy-Lefaix, M. T., Sekaki, A. H., and Gardes-Albert, M., Antioxidant actions ofGinkgo biloba extract EGb761. In: Packer, L. (Ed.), Methods in enzymology, Academic Press, San Diego, pp. 114–120 (1994).
Pannala, A., Rice-Evans, C. A., Halliwell, B., and Singh, S., Inhibition of peroxynitrite mediated tyrosine nitration by catechin polyphenols.Biochem. Biophy. Res. Commun., 232, 164–168 (1997).
Pannala, A., Razaq, R., Halliwell, B., Singh, S., and Rice-Evans, C. A., Inhibition of peroxynitrite dependent tyrosine nitration by hydroxycinnamates: Nitration or electron donation?Free Radic. Biol. Med., 24, 594–606 (1998).
Pietri, S., Maurelli, E., and Drieu, K., Cardioprotective and antioxidant effects of the terpenoid constituents ofGinkgo biloba extract (EGb 761).J. Mol. Cell. Cardiol., 29, 733–742 (1997).
Pietta, P., Simonetti, P., Gardana, C., and Mauri, P., Trolox equivalent antioxidant capacity (TEAC) ofGinkgo biloba flavonol andCamellia sinensis catechin metabolites.J. Pharm. Biomed. Anal., 23, 223–226 (2000).
Pincemail, J., Dupuis, M., Nasr, C., Han, P., Haag-Berrurier, M., Anton, R., and Deby, C., Superoxide anion scavenging effect and superoxide dismutase activity ofGinkgo biloba extract.Experientia, 45, 708–712. (1989).
Ronson, R. S., Nakamura, M., and Vinten-Johansen, J., The cardiovascular effects and implications of peroxynitrite.Cardiovasc. Res., 44, 47–59 (1999).
Scholtyssek, H., Danerau, W., Wessel, R., and Schimke, I., Antioxidative activity of ginkgolides against superoxide in an aprotic environment.Chemico-Biological Interactions, 106, 183–190 (1997).
Soung, D. Y., Kim, J. S., Chung, H. Y., Jung, H. A., Park, J. C., and Choi, J. S., Flavonoids and chlorogenic acid fromEriobotrya japonica scavenge peroxynitrite.Natural Product Sciences, 5, 80–84 (1999).
Spencer, J. P. E., Wong, J., Jenner A., Aruoma, O. I., Cross, C. E., and Halliwell, B., Base modification and strand breakage in isolated calf thymus DNA and in DNA from human skin epidermal keratinocytes exposed to peroxynitrite or 3-morpholinosydnonimine.Chem. Res. Toxicol., 9, 1152–1158 (1996).
Squadrito, G. L. and Pryor, W. A., The formation of peroxynitritein vivo from nitric oxide and superoxide.Chem. Biol. Interact., 96, 203–206 (1995).
Squadrito, G. L. and Pryor, W. A., Oxidative chemistry of nitric oxide: the roles of superoxide, peroxynitrite, and carbon dioxide.Free Radical Biol. Med., 25, 392–403 (1998).
Timmins, G. S., dos Santos, R. E., Whitwood, A. C., Catalani, L. H., Di Mascio, P., Gilbert, B. C., and Bechara, E. J., Lipid peroxidation-dependent chemiluminescence form the cyclization of alkylperoxyl radicals to dioxetane radical intermediates.Chem. Res. Toxicol., 10, 1090–1096 (1997).
Van Dyke, K., McConnell, P., and Maroquardt, L., Green tea extract and its polyphenols markedly inhibit luminol-dependent chemiluminescence activated by peroxynitrite or SIN-1.Luminescence, 15, 37–43 (2000).
Weinges, K., Hepp, M., and Jaggy, H., Isolierung und strukturaufklärung eines neuen Ginkgolids.Liebigs Ann. Chem., 521–526 (1987).
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Hyun, S.K., Jung, H.A., Chung, H.Y. et al. In vitro peroxynitrite scavenging activity of 6-hydroxykynurenic acid and other flavonoids fromGingko biloba yellow leaves. Arch Pharm Res 29, 1074–1079 (2006). https://doi.org/10.1007/BF02969294
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DOI: https://doi.org/10.1007/BF02969294