Effects of Ginkgo biloba extract (EGb 761) and quercetin on lipopolysaccharide-induced release of nitric oxide

Wadsworth, Teri L; Koop, Dennis R

doi:10.1016/s0009-2797(01)00208-3

Cited by 116Ginkgo biloba and Cashew ApplicationsImmune Response and InflammationFlavonoids in Medical Research

Effects of Ginkgo biloba extract (EGb 761) and quercetin on lipopolysaccharide-induced release of nitric oxide

Wadsworth, Teri L, Koop, Dennis R·2001·Chemico-Biological Interactions

DOI 10.1016/s0009-2797(01)00208-3

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Abstract

Administration of bacterial lipopolysaccharide (LPS) to laboratory animals and cultured macrophages is known to induce the production of nitric oxide (NO) from inducible nitric oxide synthase (iNOS). Here we show that pre-treatment with Ginkgo biloba extract (EGb 761) suppresses the in vivo production of NO (measured by the Griess reaction) after challenge with LPS. In order to begin to understand the mechanism of this inhibition, we evaluated in vitro effects of EGb 761 and its flavonoid component, quercetin, on LPS-treated RAW 264.7 macrophages. Pre-treatment with EGb 761 or quercetin dose-dependently inhibited NO release. Both substances scavenged NO generated from the decomposition of sodium nitroprusside. Western analysis showed that EGb 761 and quercetin inhibited LPS-induced levels of iNOS protein. Northern blotting demonstrated that EGb 761 and quercetin decreased LPS-induced iNOS mRNA levels without altering the half-life. Activation of mitogen activated protein kinases (MAPKs) and the redox-sensitive transcription factors, nuclear factor-kappaB (NF-kappaB) and activator protein 1 (AP-1) are key events in the signal transduction pathways mediating iNOS induction. In our studies, both EGb 761 and quercetin inhibited p38 MAPK activity, which is necessary for iNOS expression in LPS-stimulated RAW 264.7 macrophages. However, differences in the response of NF-kappaB, AP-1, and Jun N-terminal kinase/stress activated protein kinase (JNK/SAPK) and its downstream substrates to EGb 761 and quercetin suggest that quercetin is not the sole component responsible for the in vivo inhibition of LPS-induced iNOS activation by EGb 761.

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LPS activates three subclasses of MAPKs in macrophages and other cells: ERK, JNK, and p38; some compounds suppress proinflammatory cytokines and NF-κB and inhibit COX-2 and iNOS expression by inhibiting some of these MAPKs.
“In macrophages and other types of cells, LPS activates three subclasses of MAPKs: extracellular signal-regulated kinase (ERK), c-Jun-terminal kinase (JNK) and p38. Studies have revealed that some compounds are able to suppress proinflammatory cytokines and NF-κB, to inhibit the COX-2 and iNOS expression inhibiting some of these MAPKS [129,130,131].”
From Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review (2010) · cites this paper as [129]

Role of transcription factor NF-kappa B/Rel in induction of nitric oxide synthase.
Xie, Q. W., Kashiwabara, Y., & Nathan, C. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)37600-7 · Cited by 2,212 · see citing works
Antioxidant and redox regulation of gene transcription
Sen, C. K., & Packer, L. (1996) · The FASEB Journal · doi:10.1096/fasebj.10.7.8635688 · Cited by 1,996 · see citing works
Regulation of biosynthesis of nitric oxide.
Nathan, C., & Xie, Q. W. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)36703-0 · Cited by 1,669 · see citing works
Promoter of the mouse gene encoding calcium-independent nitric oxide synthase confers inducibility by interferon gamma and bacterial lipopolysaccharide.
Xie, Q. W., Whisnant, R., & Nathan, C. F. (1993) · The Journal of Experimental Medicine · doi:10.1084/jem.177.6.1779 · Cited by 1,118 · see citing works
Macrophage nitric oxide synthase gene: two upstream regions mediate induction by interferon gamma and lipopolysaccharide.
Lowenstein, C. J., Alley, E. W., Raval, P., Snowman, A. M., Snyder, S. H., Russell, S. W., & Murphy, W. J. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.20.9730 · Cited by 1,066 · see citing works
The Nitric Oxide-Scavenging Properties of Ginkgo Biloba Extract EGb 761
Marcocci, L., Maguire, J. J., Droy-Lefaix, M. T., & Packer, L. (1994) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1994.1764 · Cited by 1,053 · see citing works
Is NF-kappaB the sensor of oxidative stress?
Li, N., & Karin, M. (1999) · PubMed · Cited by 786 · see citing works
Extracellular Signal-Regulated Kinase and p38 Subgroups of Mitogen-Activated Protein Kinases Regulate Inducible Nitric Oxide Synthase and Tumor Necrosis Factor-α Gene Expression in Endotoxin-Stimulated Primary Glial Cultures
Bhat, N. R., Zhang, P., Lee, J. C., & Hogan, E. L. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-05-01633.1998 · Cited by 714 · see citing works
Is NF‐κB the sensor of oxidative stress?
Li, N., & Karin, M. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.10.1137 · Cited by 702 · see citing works
Macrophages and Inflammatory Mediators in Tissue Injury
Laskin, D. L., & Pendino, K. J. (1995) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pa.35.040195.003255 · Cited by 618 · see citing works
Ginkgo Biloba
Mh, L. T. (1996) · Cited by 600 · see citing works
Quercetin is recovered in human plasma as conjugated derivatives which retain antioxidant properties
Manach, C., Morand, C., Crespy, V., Demigné, C., Texier, O., Regerat, F., & Rémésy, C. (1998) · FEBS Letters · doi:10.1016/s0014-5793(98)00367-6 · Cited by 586 · see citing works
The Efficacy of Ginkgo biloba on Cognitive Function in Alzheimer Disease
Oken, B., Storzbach, D. M., & Kaye, J. A. (1998) · Archives of Neurology · doi:10.1001/archneur.55.11.1409 · Cited by 585 · see citing works
(-)-Epigallocatechin-3-gallate blocks the induction of nitric oxide synthase by down-regulating lipopolysaccharide-induced activity of transcription factor nuclear factor-kappaB.
Lin, Y., & Lin, J. (1997) · PubMed · Cited by 539 · see citing works
The high-output nitric oxide pathway: role and regulation
Xie, Q. W., & Nathan, C. (1994) · Journal of Leukocyte Biology · doi:10.1002/jlb.56.5.576 · Cited by 512 · see citing works
Ginkgo biloba
Kleijnen, J., & Knipschild, P. G. (1992) · The Lancet · doi:10.1016/0140-6736(92)93158-j · Cited by 464 · see citing works
(−)-Epigallocatechin-3-gallate Blocks the Induction of Nitric Oxide Synthase by Down-Regulating Lipopolysaccharide-Induced Activity of Transcription Factor Nuclear Factor-κB
Lin, Y., & Lin, J. (1997) · Molecular Pharmacology · doi:10.1124/mol.52.3.465 · Cited by 463 · see citing works
TLR6: A novel member of an expanding Toll-like receptor family
Takeuchi, O., Kawai, T., Sanjo, H., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Takeda, K., & Akira, S. (1999) · Gene · doi:10.1016/s0378-1119(99)00098-0 · Cited by 429 · see citing works
Absorption and disposition kinetics of the dietary antioxidant quercetin in man
Hollman, P. C. H., Gaag, M. V. D., Mengelers, M. J. B., van Trijp, J. M. P., de Vries, J. H. M., & Katan, M. (1996) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(96)00129-3 · Cited by 400 · see citing works
Effect of antioxidants, resveratrol, quercetin, and N -acetylcysteine, on the functions of cultured rat hepatic stellate cells and kupffer cells
Kawada, N., Seki, S., Inoue, M., & Kuroki, T. (1998) · Hepatology · doi:10.1002/hep.510270512 · Cited by 397 · see citing works
Bacterial lipopolysaccharide induces tyrosine phosphorylation and activation of mitogen-activated protein kinases in macrophages.
Weinstein, S. L., Sanghera, J. S., Lemke, K., DeFranco, A. L., & Pelech, S. L. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)42133-3 · Cited by 396 · see citing works
Specific Inhibitors of p38 and Extracellular Signal‐Regulated Kinase Mitogen‐Activated Protein Kinase Pathways Block Inducible Nitric Oxide Synthase and Tumor Necrosis Factor Accumulation in Murine Macrophages Stimulated with Lipopolysaccharide and Interferon‐γ
Ajizian, S., English, B. K., & Meals, E. A. (1999) · The Journal of Infectious Diseases · doi:10.1086/314659 · Cited by 345 · see citing works
Plasma metabolites of quercetin and their antioxidant properties
Morand, C., Crespy, V., Manach, C., Besson, C., Demigné, C., & Rémésy, C. (1998) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1998.275.1.r212 · Cited by 333 · see citing works
Oroxylin A inhibition of lipopolysaccharide-induced iNOS and COX-2 gene expression via suppression of nuclear factor-κB activation
Chen, Y., Yang, L., & Lee, T. J.-F. (2000) · Biochemical Pharmacology · doi:10.1016/s0006-2952(00)00255-0 · Cited by 323 · see citing works
Both Erk and p38 Kinases Are Necessary for Cytokine Gene Transcription
Carter, A. B., Monick, M. M., & Hunninghake, G. W. (1999) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb.20.4.3420 · Cited by 305 · see citing works
Effects of the wine polyphenolics quercetin and resveratrol on pro-inflammatory cytokine expression in RAW 264.7 macrophages
Wadsworth, T. L., & Koop, D. R. (1999) · Biochemical Pharmacology · doi:10.1016/s0006-2952(99)00002-7 · Cited by 302 · see citing works
p38 but Not p44/42 Mitogen-Activated Protein Kinase Is Required for Nitric Oxide Synthase Induction Mediated by Lipopolysaccharide in RAW 264.7 Macrophages
Chen, C., & Wang, J.-K. (1999) · Molecular Pharmacology · doi:10.1016/s0026-895x(24)12172-4 · Cited by 296 · see citing works
Constitutive and inducible nitric oxide synthases incorporate molecular oxygen into both nitric oxide and citrulline.
Leone, A., Palmer, R. M. J., Knowles, R. G., Francis, P. L., Ashton, D., & Moncada, S. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)54352-0 · Cited by 290 · see citing works
Kupffer cell activation by lipopolysaccharide in rats: Role for lipopolysaccharide binding protein and toll‐like receptor 4
Su, G. L., Klein, R., Aminlari, A., Zhang, H. Y., Steinstraesser, L., Alarcon, W. H., Remick, D., & Wang, S. C. (2000) · Hepatology · doi:10.1053/he.2000.5634 · Cited by 280 · see citing works
Pyrrolidine Dithiocarbamate Inhibits Induction of Nitric Oxide Synthase Activity in Rat Alveolar Macrophages
Sherman, M. P., Aeberhard, E. E., Wong, V., Griscavage, J. M., & Ignarro, L. J. (1993) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1993.1359 · Cited by 249 · see citing works
Transport of Quercetin and Its Glucosides across Human Intestinal Epithelial Caco-2 Cells
Walgren, R. A., Walle, U. K., & Walle, T. (1998) · Biochemical Pharmacology · doi:10.1016/s0006-2952(98)00048-3 · Cited by 249 · see citing works
Involvement of p38 mitogen‐activated protein kinase in lipopolysaccharide‐induced iNOS and COX‐2 expression in J774 macrophages
CHEN, CHEN, & Lin, W. (1999) · Immunology · doi:10.1046/j.1365-2567.1999.00747.x · Cited by 240 · see citing works
Peroxyl radical scavenging activity of Ginkgo biloba extract EGb 761
Maitra, I., Marcocci, L., Droy-Lefaix, M. T., & Packer, L. (1995) · Biochemical Pharmacology · doi:10.1016/0006-2952(95)00089-i · Cited by 238 · see citing works
Cardioprotective and Anti-oxidant Effects of the Terpenoid Constituents ofGinkgo bilobaExtract (EGb 761)
Pietri, S., Maurelli, E., Drieu, K., & Culcasi, M. (1997) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.1996.0316 · Cited by 236 · see citing works
Evidence of increased nitric oxide production in patients with the sepsis syndrome.
Evans, T. J., Carpenter, A., Kinderman, H., & Cohen, J. (1993) · PubMed · Cited by 222 · see citing works
Bioavailability of the dietary antioxidant flavonol quercetin in man
Hollman, P. C. H., van Trijp, J. M. P., Mengelers, M. J. B., de Vries, J. H. M., & Katan, M. (1997) · Cancer Letters · doi:10.1016/s0304-3835(97)04644-2 · Cited by 209 · see citing works
Quercetin inhibits inducible ICAM-1 expression in human endothelial cells through the JNK pathway
Kobuchi, H., Roy, S., Sen, C. K., Nguyen, H. G., & Packer, L. (1999) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1999.277.3.c403 · Cited by 197 · see citing works
Analysis of the Cytokine-Stimulated Human Inducible Nitric Oxide Synthase (iNOS) Gene: Characterization of Differences between Human and Mouse iNOS Promoters
Chu, S. C., Marks-Kończalik, J., Wu, H.-P., Banks, T. C., & Moss, J. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9062 · Cited by 166 · see citing works
Dual mechanism for the control of inducible-type NO synthase gene expression in macrophages during activation by interferon-gamma and bacterial lipopolysaccharide. Transcriptional and post-transcriptional regulation.
Weisz, A., Oguchi, S., Cicatiello, L., & Esumi, H. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)37197-1 · Cited by 163 · see citing works
Molecular mechanisms in the antiproliferative action of quercetin
Csókay, B., Prajda, N., Weber, G., & Oláh, E. (1997) · Life Sciences · doi:10.1016/s0024-3205(97)00230-0 · Cited by 162 · see citing works
Ginkgo biloba extract (egb 761): inhibitory effect on nitric oxide production in the macrophage cell line raw 264.7
Kobuchi, H., Droy-Lefaix, M. T., Christen, Y., & Packer, L. (1997) · Biochemical Pharmacology · doi:10.1016/s0006-2952(96)00873-8 · Cited by 154 · see citing works
Effects of Ginkgo biloba extract (EGb 761) and quercetin on lipopolysaccharide-induced signaling pathways involved in the release of tumor necrosis factor-α 1 1Abbreviations: EGb 761, Ginkgo biloba extract; LPS, lipopolysaccharide; ROIs, reactive oxygen intermediates; TNF, tumor necrosis factor; IL, interleukin; COX, cyclooxygenase; iNOS, inducible nitric oxide synthase; TLR, Toll-like receptor; LBP, lipid binding protein; NF-κB, nuclear factor-κB; IKK, IκB kinase; AP-1, activator protein 1; ATF, activating transcription factor; CRE, cyclic AMP response element; CREB, cyclic AMP binding protein; C/EBP, CCAAT/enhancer binding protein; ARE, AU-rich element; -UTR, untranslated region; MAPK, mitogen-activated protein kinase; ERK, extracellular signal-related kinase; MEKK, MAPK/ERK kinase kinase; MEK, MAPK/ERK kinase; JNK/SAPK, Jun N terminal kinase/stress-activated protein kinase; EMSA, electrophoretic mobility shift assay; DTT, dithiothreitol; PMSF, phenylmethylsulfonyl fluoride; and ECL, enhanced chemiluminescence.
Wadsworth, T. L., McDonald, T. L., & Koop, D. R. (2001) · Biochemical Pharmacology · doi:10.1016/s0006-2952(01)00734-1 · Cited by 145 · see citing works
Consumption of quercetin and kaempferol in free-living subjects eating a variety of diets
de Vrie, J. H. M., Janssen, P., Hollman, P. C. H., van Staveren, W. A., & Katan, M. (1997) · Cancer Letters · doi:10.1016/s0304-3835(97)04645-4 · Cited by 140 · see citing works
Preparation and Definition of Ginkgo Biloba Extract
Drieu, K. (1988) · Springer eBooks · doi:10.1007/978-3-642-73686-5_3 · Cited by 139 · see citing works
Current Status of Antioxidant Therapy for Alzheimer's Disease
Pitchumoni, S., & Doraiswamy, P. M. (1998) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1998.tb01544.x · Cited by 112 · see citing works
Involvement of Mitogen-Activated Protein Kinase Homologues in the Regulation of Lipopolysaccharide-Mediated Induction of Cyclo-oxygenase-2 but not Nitric Oxide Synthase in RAW 264.7 Macrophages
Paul, A., Cuenda, A., Bryant, C. E., Murray, J., Chilvers, E. R., Cohen, P., Gould, G. W., & Plevin, R. J. (1999) · Cellular Signalling · doi:10.1016/s0898-6568(99)00018-2 · Cited by 104 · see citing works
Involvement of tyrosine kinase in the induction of cyclo‐oxygenase and nitric oxide synthase by endotoxin in cultured cells
Akarasereenont, P., Mitchell, J. A., Appleton, I., Thiemermann, C., & Vane, J. R. (1994) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1994.tb17169.x · Cited by 93 · see citing works
Natural substances in psychiatry (Ginkgo biloba in dementia).
Itil, T. M., & Martorano, D. (1995) · PubMed · Cited by 83 · see citing works
Radicicol suppresses expression of inducible nitric-oxide synthase by blocking p38 kinase and nuclear factor-kappaB/Rel in lipopolysaccharide-stimulated macrophages.
Jeon, Y. J., Kim, Y. K., Lee, M., Park, S. M., Han, S., & Kim, H. M. (2000) · PubMed · Cited by 79 · see citing works
Down-Regulation of Cytochrome P450 mRNAs and Proteins in Mice Lacking a Functional NOS2 Gene
Sewer, M. B., Barclay, T. B., & Morgan, E. T. (1998) · Molecular Pharmacology · doi:10.1124/mol.54.2.273 · Cited by 74 · see citing works
Endotoxin opens the Toll gates to innate immunity
Ulevitch, R. J. (1999) · Nature Medicine · doi:10.1038/5504 · Cited by 70 · see citing works
Ginkgo biloba extract inhibits oxygen species production generated by phorbol myristate acetate stimulated human leukocytes
Pincemail, J., Thirion, A., Dupuis, M., Braquet, P. G., Drieu, K., & Deby, C. M. T. (1987) · Cellular and Molecular Life Sciences · doi:10.1007/bf01942843 · Cited by 65 · see citing works
Effect of antiproliferative flavonoids on ascorbic acid accumulation in human colon adenocarcinoma cells
Kuo, S., Morehouse, H. F., & Lin, C.-P. (1997) · Cancer Letters · doi:10.1016/s0304-3835(97)00183-3 · Cited by 56 · see citing works
Effects of Ginkgo biloba extract and preconditioning on the diabetic rat myocardium
Tósaki, Á., Páli, T., & Droy-Lefaix, M. T. (1996) · Diabetologia · doi:10.1007/s001250050567 · Cited by 51 · see citing works
Effects of quercetin on drug metabolizing enzymes and oxidation of 2', 7-dichlorofluorescin in HepG2 cells
Musonda, C., Helsby, N. A., & Chipman, J. (1997) · Human & Experimental Toxicology · doi:10.1177/096032719701601202 · Cited by 37 · see citing works
Bilobalide, a constituent of Ginkgo biloba L., potentiates drug-metabolizing enzyme activities in mice: possible mechanism for anticonvulsant activity against 4-O-methylpyridoxine-induced convulsions.
Sasaki, K., Wada, K., Hatta, S., Ohshika, H., & Masanobu, H. A. G. A. (1997) · PubMed · Cited by 31 · see citing works
EGb 761 and the Recovery of Ion Imbalance in Ischemic Reperfused Diabetic Rat Retina
Szabo, M. E., Droy-Lefaix, M. T., & Doly, M. (2009) · Ophthalmic Research · doi:10.1159/000267606 · Cited by 17 · see citing works
2-Amino-3-methylimidazo[4,5-f]quinoline inhibits nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 cells by blocking p38 kinase activation
Lee, Y. (2000) · Cancer Letters · doi:10.1016/s0304-3835(00)00452-3 · Cited by 14 · see citing works
Bio‐normalizer modulates interferon‐γ‐induced nitric oxide production in the mouse macrophage cell line RAW 264.7
Kobuchi, H., & Packer, L. (1997) · IUBMB Life · doi:10.1080/15216549700203911 · Cited by 11 · see citing works

Flagged first, then by citations

3 of the 62 references couldn’t be matched to a known paper.

Sorted by citations

Anti-inflammatory Plant Flavonoids and Cellular Action Mechanisms
Kim, H. P., Son, K. H., Chang, H. W., & Kang, S. S. (2004) · Journal of Pharmacological Sciences · doi:10.1254/jphs.crj04003x · Cited by 1,018 · see citing works
Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review
Miguel, M. G. (2010) · Molecules · doi:10.3390/molecules15129252 · Cited by 933 · see citing works
Flavonoids as anti-inflammatory agents
Serafini, M., Peluso, I., & Raguzzini, A. (2010) · Proceedings of The Nutrition Society · doi:10.1017/s002966511000162x · Cited by 826 · see citing works
Inflammatory Disease Processes and Interactions with Nutrition
Calder, P. C., Albers, R., Antoine, J., Blum, S., Bourdet‐Sicard, R., Ferns, G. A., Folkerts, G., Friedmann, P. S., Frost, G. S., Guarner, F., et al. (2009) · British Journal Of Nutrition · doi:10.1017/s0007114509377867 · Cited by 570 · see citing works
“Quercetin has been shown to affect iNOS expression by inhibiting p38 MAPK and TNF-a from LPS-induced RAW cells by inhibiting jun N-terminal kinase/SAPK and Ap-1 DNA binding((376,377)).”
Background
Fruit polyphenols, immunity and inflammation
González-Gallego, J., García-Mediavilla, M. V., Sánchez-Campos, S., & Tuñón, M. J. (2010) · British Journal Of Nutrition · doi:10.1017/s0007114510003910 · Cited by 387 · see citing works
“It has been shown that quercetin inhibits iNOS expression through inhibition of p38 MAPK and blocks AP-1 binding in LPS-induced RAW cells by inhibiting c-Jun N-terminal kinase((60)).”
Background
Polyphenols, intracellular signalling and inflammation.
Santangelo, C., Varı́, R., Scazzocchio, B., Benedetto, R. D., Filesi, C., & Masella, R. (2007) · PubMed · Cited by 369 · see citing works
Neuroprotective effects of Ginkgo biloba extract
Ahlemeyer, B., & Krieglstein, J. (2003) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-003-3080-1 · Cited by 368 · see citing works
Quercetin Decreases Oxidative Stress, NF-κB Activation, and iNOS Overexpression in Liver of Streptozotocin-Induced Diabetic Rats
Dias, A. S., Porawski, M., Alonso-Chamorro, M., Marroni, N. P., Collado, P. S., & González‐Gallego, J. (2005) · Journal of Nutrition · doi:10.1093/jn/135.10.2299 · Cited by 318 · see citing works
Effects of Astaxanthin on Lipopolysaccharide-Induced Inflammation In Vitro and In Vivo
Ohgami, K., Shiratori, K., Kotake, S., Nishida, T., Mizuki, N., Yazawa, K., & Ohno, S. (2003) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.02-0822 · Cited by 307 · see citing works
“After exposure to endogenous and exogenous stimulators, iNOS is induced quantitatively in various cells, such as macrophages, smooth muscle cells, and hepatocytes to trigger several disadvantageous cellular responses and cause inflammation.(15) Therefore, NO production induced by iNOS may reflect the degree of inflamm…”
Background
Ginkgo biloba extracts and cancer: a research area in its infancy
DeFeudis, F. V., Papadopoulos, V., & Drieu, K. (2003) · Fundamental and Clinical Pharmacology · doi:10.1046/j.1472-8206.2003.00156.x · Cited by 231 · see citing works
Effects of fucoxanthin on lipopolysaccharide-induced inflammation in vitro and in vivo
Shiratori, K., Ohgami, K., Ilieva, I. B., Jin, X.-H., Koyama, Y., Miyashita, K., Yoshida, K., Kase, S., & Ohno, S. (2005) · Experimental Eye Research · doi:10.1016/j.exer.2005.03.002 · Cited by 218 · see citing works
Anthocyanins: Antioxidant and/or anti-inflammatory activities
Miguel, M. G. (2011) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) · Cited by 217 · see citing works
Dandelion (Taraxacum officinale) flower extract suppresses both reactive oxygen species and nitric oxide and prevents lipid oxidation in vitro
Hu, C., & Kitts, D. D. (2005) · Phytomedicine · doi:10.1016/j.phymed.2003.12.012 · Cited by 202 · see citing works
“Similar inhibitory activities have been reported with other standardized phenolicrich food (Hu et al., 2003) and herbal extracts, such as Ginkgo biloba extract (Wadsworth and Koop, 2001).”
Background
Anti-inflammatory properties of dietary flavonoids.
González‐Gallego, J., Sánchez‐Campos, S., & Tuñón, M. J. (2007) · PubMed · Cited by 200 · see citing works
Luteolin and luteolin-7-O-glucoside from dandelion flower suppress iNOS and COX-2 in RAW264.7 cells
Hu, C., & Kitts, D. D. (2004) · Molecular and Cellular Biochemistry · doi:10.1023/b:mcbi.0000044364.73144.fe · Cited by 187 · see citing works
“Plant extracts, rich in flavonoids (such as Ginkgo biloba extract EGb761) also suppress the expression of iNOS and the COX-2 protein [28].”
Background
Antimicrobial, Antioxidant, and Anti-Inflammatory Activities of Essential Oils from Five Selected Herbs
Mei-Lin, T. S. A. I., Lin, C., Lin, W., & Yang, C. (2011) · Bioscience Biotechnology and Biochemistry · doi:10.1271/bbb.110377 · Cited by 179 · see citing works
Inhibitory effect of naringin on lipopolysaccharide (LPS)-induced endotoxin shock in mice and nitric oxide production in RAW 264.7 macrophages
Kanno, S., Shouji, A., Tomizawa, A., Hiura, T., Osanai, Y., Ujibe, M., Obara, Y., Nakahata, N., & Ishikawa, M. (2005) · Life Sciences · doi:10.1016/j.lfs.2005.04.051 · Cited by 163 · see citing works
Ginkgo bilobaExtract Inhibits Tumor Necrosis Factor-α–Induced Reactive Oxygen Species Generation, Transcription Factor Activation, and Cell Adhesion Molecule Expression in Human Aortic Endothelial Cells
Chen, J., Chen, Y., Lin, F.-Y., Chen, Y., & Lin, S. (2003) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000089012.73180.63 · Cited by 140 · see citing works
Evaluation of Antioxidant Activity and Inhibitory Effect on Nitric Oxide Production of Some Common Vegetables
Bor, J.-Y., Chen, H.-Y., & Yen, G. (2006) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf0527448 · Cited by 135 · see citing works
Anti-inflammatory Effects of Aronia Extract on Rat Endotoxin-Induced Uveitis
Ohgami, K., Ilieva, I. B., Shiratori, K., Koyama, Y., Jin, X.-H., Yoshida, K., Kase, S., Kitaichi, N., Suzuki, Y., Tanaka, T., et al. (2004) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.04-0715 · Cited by 136 · see citing works
“endogenous and exogenous stimulators, iNOS is induced quantitatively in various cells, such as macrophages, smooth muscle cells, and hepatocytes, and triggers several disadvantageous cellular responses that can cause inflammation and stroke.(26) The level of NO production induced by iNOS may reflect the degree of infl…”
Background
Ginkgo biloba Extract in Vascular Protection: Molecular Mechanisms and Clinical Applications
Tian, J., Liu, Y., & Chen, K. (2017) · Current Vascular Pharmacology · doi:10.2174/1570161115666170713095545 · Cited by 133 · see citing works
Effects of Quercetin on Liver Damage in Rats with Carbon Tetrachloride-Induced Cirrhosis
Pavanato, A., Tuñón, M. J., Sánchez‐Campos, S., Marroni, C. A., Llesuy, S., González‐Gallego, J., & Marroni, N. P. (2003) · Digestive Diseases and Sciences · doi:10.1023/a:1022869716643 · Cited by 133 · see citing works
“This compound has been reported to scavenge superoxide in ischemia–reperfusion injury (6); to protect against oxidative stress induced by ultraviolet light (7), spontaneous hypertension (8), and bacterial lipopolysaccharide (9); and to inhibit angiogenesis (10) and carcinogenesis (11).”
Background
The effects of dietary flavonoids on the regulation of redox inflammatory networks
Izzi, V. (2012) · Frontiers in bioscience · doi:10.2741/4061 · Cited by 133 · see citing works
Activation of Autoimmunity Following Use of Immunostimulatory Herbal Supplements
Lee, A. N., & Werth, V. P. (2004) · Archives of Dermatology · doi:10.1001/archderm.140.6.723 · Cited by 123 · see citing works
Heat Shock Protein 70 Is a Potential Virulence Factor in Murine Toxoplasma Infection Via Immunomodulation of Host NF-κB and Nitric Oxide
Dobbin, C. A., Smith, N. C., & Johnson, A. M. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.2.958 · Cited by 117 · see citing works
Neem (Azadirachta indica) leaf mediated immune activation causes prophylactic growth inhibition of murine Ehrlich carcinoma and B16 melanoma
Baral, R., & Chattopadhyay, U. (2003) · International Immunopharmacology · doi:10.1016/j.intimp.2003.09.006 · Cited by 105 · see citing works
Phenolic compounds as antidiabetic, anti‐inflammatory, and anticancer agents and improvement of their bioavailability by liposomes
Tatipamula, V. B., & Kukavica, B. M. (2021) · Cell Biochemistry and Function · doi:10.1002/cbf.3667 · Cited by 101 · see citing works
Effective Separation of Potent Antiproliferation and Antiadhesion Components from Wild Blueberry (Vaccinium angustifolium Ait.) Fruits
Schmidt, B. M., Howell, A. B., McEniry, B., Knight, C. T. G., Seigler, D. S., Erdman, J. W., & Lila, M. A. (2004) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf049238n · Cited by 96 · see citing works
Chemical Composition and Biological Properties of Essential Oils of Two Mint Species
Ml, T., Wu, C., Lin, T., Lin, W., Huang, Y., & Yang, C. (2013) · Tropical Journal of Pharmaceutical Research · doi:10.4314/tjpr.v12i4.20 · Cited by 95 · see citing works
“The absorbance was determined at 540 nm [12], and NO radical scavenging activity (NO) was obtained as in Eq 3 NO (%) = {(Ab- As)/Ab}100 .”
Method
Quercetin prevents oxidative stress and NF-κB activation in gastric mucosa of portal hypertensive rats
Moreira, A. J., Fraga, C., Alonso-Chamorro, M., Collado, P. S., Zetller, C., Marroni, C. A., Marroni, N. P., & González‐Gallego, J. (2004) · Biochemical Pharmacology · doi:10.1016/j.bcp.2004.07.016 · Cited by 93 · see citing works
Ginkgo biloba extract EGb 761 has anti-inflammatory properties and ameliorates colitis in mice by driving effector T cell apoptosis
Kotakadi, V. S., Yu, J. H., Hofseth, A. B., Ying, L., Cui, X., Volate, S. R., Chumanevich, A. A., Wood, P. A., Price, R. L., McNeal, A., et al. (2008) · Carcinogenesis · doi:10.1093/carcin/bgn143 · Cited by 93 · see citing works
“Mechanistically, we show that EGb 761 can suppress the activation of macrophages (Figure 1). Consistent with this, others have shown EGb 761 to decrease the expression of iNOS, release of nitric oxide, as well as inhibit other markers of inflammation such as Cox-2 and nuclear factor-kappa B (11,33, 34 ).”
Result
Nrf-2 mediated heme oxygenase-1 expression, an antioxidant-independent mechanism, contributes to anti-atherogenesis and vascular protective effects of Ginkgo biloba extract
Chen, J.-S., Huang, P., Wang, C., Lin, F., Tsai, H., Wu, T.-C., Lin, S., & Chen, J. (2010) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2010.11.010 · Cited by 91 · see citing works
Britanin suppresses LPS-induced nitric oxide, PGE2 and cytokine production via NF-κB and MAPK inactivation in RAW 264.7 cells
Park, H.-H., Kim, M. J., Li, Y., Park, Y. N., Lee, J., Lee, Y. J., Kim, S.-G., Park, H., Son, J. K., Chang, H. W., et al. (2012) · International Immunopharmacology · doi:10.1016/j.intimp.2012.12.005 · Cited by 85 · see citing works
Preventive Effect of Ginkgo biloba Extract (GBB) on the Lipopolysaccharide-Induced Expressions of Inducible Nitric Oxide Synthase and Cyclooxygenase-2 via Suppression of Nuclear Factor-.KAPPA.B in RAW 264.7 Cells
Park, Y.-M., Won, J., Yun, K., Ryu, J.-H., Han, Y.-N., Choi, S.-K., & Lee, K. (2006) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.29.985 · Cited by 83 · see citing works
The effects of Ginkgo biloba extract on lipopolysaccharide-induced inflammation in vitro and in vivo
Ilieva, I. B., Ohgami, K., Shiratori, K., Koyama, Y., Yoshida, K., Kase, S., Kitamei, H., Takemoto, Y., Yazawa, K., & Ohno, S. (2004) · Experimental Eye Research · doi:10.1016/j.exer.2004.03.009 · Cited by 83 · see citing works
Nitric oxide as a target of complementary and alternative medicines to prevent and treat inflammation and cancer.
Hofseth, L. (2008) · Cancer Letters · doi:10.1016/j.canlet.2008.03.024 · Cited by 80 · see citing works
Natural Compounds and Plant Extracts as Therapeutics Against Chronic Inflammation in Alzheimer’s Disease – A Translational Perspective
Apetz, N., Münch, G. W., Govindaraghavan, S., & Gyengési, E. (2014) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527313666140917110635 · Cited by 72 · see citing works
“7 macrophages and C57BL/6 mice by inhibiting LPS-induced rises in iNOS levels [168].”
Background
Hormonal regulation of pro-inflammatory and lipid peroxidation processes in liver of old ovariectomized female rats
Kireev, R. A., Tresguerres, A. C. F., Garcı́a, C., Borrás, C., Ariznavarreta, C., Vara, E., Viña, J., & Tresguerres, J. A. F. (2009) · Biogerontology · doi:10.1007/s10522-009-9242-2 · Cited by 66 · see citing works
“So, quercetin reduced iNOS expression by inhibiting p38 MAPK ( Wadsworth and Koop 2001 ) and blocked TNF-a-induction from LPS-induced RAW cells by suppressing JNK/SAPK, leading to the reduction of AP-1-DNA binding (Wadsworth et al. 2001).”
Background
Ginkgo biloba inhibits bleomycin-induced lung fibrosis in rats
Iraz, M., Erdoğan, H., Kotuk, M., Yağmurca, M., Kılıç, T., Ermiş, H., Fadıllıoğlu, E., & Yıldırım, Z. (2006) · Pharmacological Research · doi:10.1016/j.phrs.2005.12.009 · Cited by 61 · see citing works
Nitric oxide production, inhibitory, antioxidant and antimycobacterial activities of the fruits extract and flavonoid content of Schinus terebinthifolius
Bernardes, N. R., de Araújo, M. H., Borges, I. F. J. C., Almeida, F. M., Amaral, E. P., Lasunskaia, E., Muzitano, M. F., & de Oliveira, D. B. (2014) · Revista Brasileira de Farmacognosia · doi:10.1016/j.bjp.2014.10.012 · Cited by 55 · see citing works
“The physiological NO production is extremely important to defend the body; however, its overproduction and metabolites have been implicated in the development of pathologies, such as bacterial septic shock and chronic inflammation (Wadsworth and Koop, 2001).”
Background
Protective Role of Quercetin on PCBs-Induced Oxidative Stress and Apoptosis in Hippocampus of Adult Rats
Selvakumar, K., Bavithra, S., Suganthi, M., Selvanesan, B. C., Perumal, E., Arunkumar, R., Krishnamoorthy, G., Venkataraman, P., & Arunakaran, J. (2011) · Neurochemical Research · doi:10.1007/s11064-011-0661-5 · Cited by 56 · see citing works
Anti-inflammatory effects of Ginkgo biloba extract against trimethyltin-induced hippocampal neuronal injury
Kaur, S., Sharma, N., & Nehru, B. (2017) · Inflammopharmacology · doi:10.1007/s10787-017-0396-2 · Cited by 54 · see citing works
Antioxidant capacity in Ginkgo biloba
Goh, L. M. L., & Barlow, P. J. (2002) · Food Research International · doi:10.1016/s0963-9969(02)00084-4 · Cited by 54 · see citing works
Protective Effect of Quercetin in LPS-Induced Murine Acute Lung Injury Mediated by cAMP-Epac Pathway
Wang, X., Song, S., Li, Y., Hu, Z., Zhang, Z., Yan, C., Li, Z.-G., & Tang, H. (2018) · Inflammation · doi:10.1007/s10753-018-0761-3 · Cited by 51 · see citing works
“7 [27], BV2 [28], and rat peritoneal macrophages [29].”
Hepatoprotective activity of quercetin against acrylonitrile‐induced hepatotoxicity in rats
Abo‐Salem, O. M., Abd‐Ellah, M. F., & Ghonaim, M. (2011) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.20406 · Cited by 51 · see citing works
Protective effect of 1,2,4-benzenetriol on LPS-induced NO production by BV2 microglial cells
Hou, R. C., Chen, Y.-S., Chen, C., Chen, Y.-H., & Jeng, K.-C. G. (2005) · Journal of Biomedical Science · doi:10.1007/s11373-005-9039-5 · Cited by 51 · see citing works
“Thus, the mechanism of inhibition of LPS-induced iNOS expression by BT might be similar to sesamol and other polyphenol antioxidants that selectively inhibit p38 MAPK [20, 34].”
Background
Natural compounds: evidence for a protective role in eye disease
Ritch, R. H. (2007) · Canadian Journal of Ophthalmology · doi:10.3129/can.j.ophthalmol.i07-044 · Cited by 47 · see citing works
Protective effects ofGinkgo bilobaL. against natural toxins, chemical toxicities, and radiation: A comprehensive review
Omidkhoda, S. F., Razavi, B. M., & Hosseinzadeh, H. (2019) · Phytotherapy Research · doi:10.1002/ptr.6469 · Cited by 47 · see citing works
“Based on all these studies, totally, GB possesses notable antiinflammatory influences, which are at the transcriptional level and via NF ‐ κ B/AP ‐ 1, MAPKs, COX ‐ 2/PGE2, and iNOS/NO pathways (Ilieva et al., 2004; Jang et al., 2012; Park et al., 2006; Ryu et al., 2012; Wadsworth & Koop, 2001; Wadsworth, McDonald, & K…”
Influential
Homocysteine stimulates inducible nitric oxide synthase expression in macrophages: Antagonizing effect of ginkgolides and bilobalide
Woo, C. W., Cheung, F., Chan, V. W. H., Siow, Y. L., & Karmin, O. (2003) · Molecular and Cellular Biochemistry · doi:10.1023/a:1021601512058 · Cited by 45 · see citing works
“While the present study focused on the antagonizing effect of EGb and its terpenoids on homocysteine-induced iNOS expression, the other components in EGb such as quercetin (flavonoid) were also shown to have free radical scavenging properties [48].”
Background
Can Compounds of Natural Origin Be Important in Chemoprevention? Anticancer Properties of Quercetin, Resveratrol, and Curcumin—A Comprehensive Review
Cecerska‐Heryć, E., Wiśniewska, Z., Serwin, N. M., Polikowska, A., Goszka, M., Engwert, W., Michałów, J., Pękała, M., Budkowska, M., Michalczyk, A., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25084505 · Cited by 48 · see citing works
“Lymphoma [169] In vitro LPS Reduction of ROS and NO Leukemia [172] In vivo Testosterone, MNU Reduction of lipid peroxidation Prostate cancer [179] In vitro – Reduction of lipid peroxidation (effect combined with selenium) Endometrial cancer [181] In vitro TNF [181], ethanol [183] Inhibition of ROS…”
Background
Chlorella dichloromethane extract ameliorates NO production and iNOS expression through the down-regulation of NFκB activity mediated by suppressed oxidative stress in RAW 264.7 macrophages
Park, J., Cho, H.-Y., Kim, J.-K., Noh, K., Yang, J.-R., Ahn, J.-M., Lee, M.-O., & Song, Y. (2004) · Clinica Chimica Acta · doi:10.1016/j.cccn.2004.09.013 · Cited by 43 · see citing works
Quercetin decreases steroidogenic enzyme activity, NF-κB expression, and oxidative stress in cultured Leydig cells exposed to atrazine
Abarikwu, S. O., Pant, A. B., & Farombi, E. O. (2012) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-012-1471-z · Cited by 41 · see citing works
Antibacterial Activities ofGinkgo bilobaL. Leaf Extracts
Sati, S. C., & Joshi, S. (2011) · The Scientific World JOURNAL · doi:10.1100/2011/545421 · Cited by 41 · see citing works
“Research Article TheScientificWorldJOURNAL (2011) 11, 2237–2242 ISSN 1537-744X; doi:10.1100/2011/545421 Antibacterial Activities of Ginkgo biloba”
BackgroundInfluential
Ginkgo biloba extract reduces high-glucose-induced endothelial reactive oxygen species generation and cell adhesion molecule expression by enhancing HO-1 expression via Akt/eNOS and p38 MAP kinase pathways
Tsai, H., Huang, P., Lin, F., Chen, J.-S., Lin, S., & Chen, J. (2013) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2013.01.002 · Cited by 40 · see citing works
Anti-Inflammatory and Immunomodulatory Properties of Dietary Flavonoids
González‐Gallego, J., García‐Mediavilla, M. V., Sánchez‐Campos, S., & Tuñón, M. J. (2013) · Polyphenols in Human Health and Disease · doi:10.1016/b978-0-12-398456-2.00032-3 · Cited by 38 · see citing works
Proximate Composition, Polyphenol Content and Anti-inflammatory Properties of White and Pigmented Italian Rice Varieties
Petroni, K., Landoni, M., Tomay, F., Calvenzani, V., Simonelli, C., & Cormegna, M. (2017) · Universal Journal of Agricultural Research · doi:10.13189/ujar.2017.050509 · Cited by 36 · see citing works
“Similar findings of a flavonoid rich-extract reducing the expression of iNOS protein and corresponding transcript have been reported with extracts from black rice bran fraction or Ginko biloba in vitro [30, 31].”
Result
Ginkgolide A, B, and huperzine A inhibit nitric oxide-induced neurotoxicity
Zhao, H., & Li, X. (2002) · International Immunopharmacology · doi:10.1016/s1567-5769(02)00093-0 · Cited by 36 · see citing works
Ginkgo biloba Extract Attenuates Hyperalgesia in a Rat Model of Vincristine-Induced Peripheral Neuropathy
Park, H. J., Lee, H. G., Kim, Y. S., Lee, J. Y., Jeon, J. P., Park, C., & Moon, D. E. (2012) · Anesthesia & Analgesia · doi:10.1213/ane.0b013e318262e170 · Cited by 35 · see citing works
Bilobalide, a unique constituent of Ginkgo biloba, inhibits inflammatory pain in rats
Goldie, M., & Dolan, S. (2013) · Behavioural Pharmacology · doi:10.1097/fbp.0b013e32836360ab · Cited by 35 · see citing works
“…prostaglandin E2 (Ilieva et al., 2004), tumour necrosis factor-a (Wadsworth et al., 2001a; Ilieva et al., 2004) and inducible nitric oxide synthase (Wadsworth and Koop, 2001b; Ilieva et al., 2004); however, bilobalide has a lesser effect, although one study has shown a decrease in inducible nitric…”
Background
Complementary therapy for the treatment of glaucoma: a perspective.
Ritch, R. H. (2005) · PubMed · doi:10.1016/j.ohc.2005.07.004 · Cited by 35 · see citing works
“[144] Wadsworth TL, Koop D.”
Background
Effects of Ginkgo biloba extract (EGb 761) on gene expression: Possible relevance to neurological disorders and age‐associated cognitive impairment
DeFeudis, F. V. (2002) · Drug Development Research · doi:10.1002/ddr.10151 · Cited by 35 · see citing works
Pharmacokinetic, Metabolism, and Metabolomic Strategies Provide Deep Insight Into the Underlying Mechanism of Ginkgo biloba Flavonoids in the Treatment of Cardiovascular Disease
Tao, Y., Zhu, F., Pan, M., Liu, Q., & Wang, P. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.857370 · Cited by 34 · see citing works
Down-regulation of NF-κB signalling by polyphenolic compounds prevents endotoxin-induced liver injury in a rat model
Bharrhan, S., Chopra, K., Arora, S. K., Toor, J. S., & Rishi, P. (2011) · Innate Immunity · doi:10.1177/1753425910393369 · Cited by 34 · see citing works
Anti-inflammatory medicinal plants and the molecular mechanisms underlying their activities
Nworu, C. S., & Akah, P. A. (2015) · African Journal of Traditional Complementary and Alternative Medicines · doi:10.4314/ajtcam.v12i6.3s · Cited by 32 · see citing works
The Effects of Naringin and Naringenin on Endotoxin-Induced Uveitis in Rats
Shiratori, K., Ohgami, K., Ilieva, I. B., Jin, X.-H., Yoshida, K., Kase, S., & Ohno, S. (2005) · Journal of Ocular Pharmacology and Therapeutics · doi:10.1089/jop.2005.21.298 · Cited by 32 · see citing works
Modulation of inflammation-related genes of polysaccharides fractionated from mycelia of medicinal basidiomycete Antrodia camphorata
Wu, Y.-Y., Chen, C.-C., Chyau, C., Chung, S., & Liu, Y.-W. (2007) · Acta Pharmacologica Sinica · doi:10.1111/j.1745-7254.2007.00500.x · Cited by 33 · see citing works
Anti-Neuroinflammatory Effects of Ginkgo biloba Extract EGb 761 in LPS-Activated BV2 Microglial Cells
Sun, L., Apweiler, M., Tirkey, A., Klett, D., Normann, C., Dietz, G. P. H., Lehner, M. D., & Fiebich, B. L. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25158108 · Cited by 28 · see citing works
“Furthermore, EGb 761 decreases iNOS expression partially mediated via the suppression of p38 MAPK, which is essential for iNOS expression [46].”
BackgroundInfluential
Potentialities of Ginkgo extract on toxicants, toxins, and radiation: a critical review
Boateng, I. D. (2022) · Food & Function · doi:10.1039/d2fo01298g · Cited by 27 · see citing works
Therapeutic Versus Preventative Use of Ginkgo biloba Extract (EGb 761) against Indomethacin-Induced Gastric Ulcer in Mice
Abd-Eldayem, A. M., Alnasser, S. M., Abd‐Elhafeez, H. H., Soliman, S. A., & Abdel‐Emam, R. A. (2022) · Molecules · doi:10.3390/molecules27175598 · Cited by 27 · see citing works
“Thus, the inhibition of NF-κB subsequently inhibits the gene transcription of IL-6, TNF-α, and other inflammatory cytokines [73].”
Background
Antiapoptotic Effects of EGb 761
Serrano‐García, N., Pedraza‐Chaverrí, J., Mares-Sámano, J. J., Orozco‐Ibarra, M., Cruz-Salgado, A., Jiménez‐Anguiano, A., Sotelo, J., & Trejo‐Solís, C. (2013) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2013/495703 · Cited by 30 · see citing works
Oral administration of Ginkgo biloba extract, EGb‐761 inhibits thermal hyperalgesia in rodent models of inflammatory and post‐surgical pain
Biddlestone, L., Corbett, A. D., & Dolan, S. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707220 · Cited by 27 · see citing works
“The mechanism of action of Ginkgo biloba extracts have not been fully determined but there is considerable evidence to show that they block induction of iNOS and release of NO in in vitro and in vivo models (Wadsworth and Koop, 2001a, b; Ilieva et al., 2004).”
BackgroundResultInfluential
Inhibitory Action of Quercetin on Eosinophil ActivationIn Vitro
Sakai, M., & Asano, K. (2013) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2013/127105 · Cited by 26 · see citing works
A novel antioxidant, octyl caffeate, suppression of LPS/IFN-γ-induced inducible nitric oxide synthase gene expression in rat aortic smooth muscle cells
Hsiao, G., Shen, M., Chang, W., Cheng, Y., Pan, S., Kuo, Y., Chen, T., & Sheu, J. (2003) · Biochemical Pharmacology · doi:10.1016/s0006-2952(03)00070-4 · Cited by 24 · see citing works
Modulation of Th1/Th2 Cytokine Balance by Quercetin In Vitro
Tanaka, Y., Furuta, A., Asano, K., & Kobayashi, H. (2020) · Medicines · doi:10.3390/medicines7080046 · Cited by 23 · see citing works
“After oral administration of quercetin at 1200 mg, which is a standard recommended dosage, plasma levels of quercetin gradually increase and peak at 12 μM [22,23], which is a much higher level than that which caused modulation of cytokine production by CD4+ T cells after IL-4 stimulation in vitro in this study.”
Background
Inhibition of nitric oxide production from lipopolysaccharide-treated RAW 264.7 cells by synthetic flavones: Structure-activity relationship and action mechanism
Kim, S. J., Park, H., & Kim, H. P. (2004) · Archives of Pharmacal Research · doi:10.1007/bf02975847 · Cited by 23 · see citing works
Cedrela sinensis Leaves Suppress Oxidative Stress and Expressions of iNOS and COX-2 via MAPK Signaling Pathways in RAW 264.7 Cells
Bak, M.-J., Jeong, J.-H., Kang, H.-S., Jin, K.-S., Ok, S., & Jeong, W. (2009) · Preventive Nutrition and Food Science · doi:10.3746/jfn.2009.14.4.269 · Cited by 22 · see citing works
Quercetin Enhances the Thioredoxin Production of Nasal Epithelial Cells In Vitro and In Vivo
Edo, Y., Otaki, A., & Asano, K. (2018) · Medicines · doi:10.3390/medicines5040124 · Cited by 22 · see citing works
“Although there is no standard recommended dosage of quercetin, a dose of 1200 to 1500 mg per day is commonly used [26] as a supplement.”
Background
Ginkgo biloba extract suppresses endotoxin-mediated monocyte activation by inhibiting nitric oxide- and tristetraprolin-mediated toll-like receptor 4 expression
Lee, Y., Lin, J., Chang, C., Chen, Y., Liu, P., Lee, A.-W., Tsai, J.-C., Li, C., Tsai, C., Chen, T.-L., et al. (2010) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2010.03.002 · Cited by 21 · see citing works
Polyphenols Suppress and Modulate Inflammation
Kim, J., Lee, K. W., & Lee, H. J. (2013) · Polyphenols in Human Health and Disease · doi:10.1016/b978-0-12-398456-2.00029-3 · Cited by 20 · see citing works
Optimization of multi-stage countercurrent extraction of antioxidants from Ginkgo biloba L. leaves
Yu, C.-H., Chen, J., Yao-kang, X., Li, X.-X., Dai, X., & Shi, C. (2011) · Food and Bioproducts Processing · doi:10.1016/j.fbp.2011.05.003 · Cited by 19 · see citing works
Central and Local Administration of Gingko Biloba Extract EGb 761® Inhibits Thermal Hyperalgesia and Inflammation in the Rat Carrageenan Model
Biddlestone, L., Goldie, M., & Dolan, S. (2011) · Anesthesia & Analgesia · doi:10.1213/ane.0b013e3182117440 · Cited by 19 · see citing works
Effect of Pinus massoniana bark extract on IFN-γ-induced ICAM-1 expression in HaCaT human keratinocytes
Chun-lian, W., Feng, D., Ma, H., Xie, H., Wang, H., & Wang, J. (2008) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2008.11.024 · Cited by 17 · see citing works
Effect of Ginkgo biloba extract EGb 761 on the nonspecific and humoral immune responses in a hypothalamic–pituitary–adrenal axis activation model
Villaseñor-Garcı́a, M. M., Lozoya, X., Osuna, L., Paredes, J. M. V., Sandoval-Ramı́rez, L., & Puebla‐Pérez, A. M. (2004) · International Immunopharmacology · doi:10.1016/j.intimp.2004.05.014 · Cited by 17 · see citing works
Quercetin modulates iNOS, eNOS and NOSTRIN expressions and attenuates oxidative stress in warm hepatic ischemia-reperfusion injury in rats
Abd-Elbaset, M., Arafa, E. A., Sherbiny, G. A. E., Abdel‐Bakky, M. S., & Elgendy, A. N. A. M. (2015) · Beni-Suef University Journal of Basic and Applied Sciences · doi:10.1016/j.bjbas.2015.07.001 · Cited by 15 · see citing works
A bibliometric and thematic analysis of the trends in the research on ginkgo biloba extract from 1985 to 2022
Ji, H., Zhou, X.-H., Wu, H., Liu, H., & Zhang, G. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e21214 · Cited by 14 · see citing works
“…of flavonoid kaempferol found in GBE in the early stage in the top 20 most frequent keywords, which shows that GBE was considered a potential anti-inflammatory agent, inhibit nitric oxide production under tissue-damaging inflammatory conditions from the initial stages of research [50,51] (Fig.”
Background
Protective Effect of Ginkgo Biloba Extract and Pumpkin Seed Oil Against Neurotoxicity of Rotenone in Adult Male Rats
Ahmed, H. H., Abdel-Rahman, M., Ali, R. S., & Moniem, A. E. A. (2009) · The Journal of applied sciences research · Cited by 14 · see citing works
Systemic and topical Ginkgo biloba leaf extract (Egb-761) ameliorated rat paw inflammation in comparison to dexamethasone
Abdel‐Emam, R. A., & Abd-Eldayem, A. M. (2021) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2021.114619 · Cited by 13 · see citing works
Dietary Flavonoid Quercetin Supplement Promotes Antiviral Innate Responses Against Vesicular Stomatitis Virus Infection by Reshaping the Bacteriome and Host Metabolome in Mice
Li, T., Zhu, J., Yu, Q., Zhu, Y., Wu, C., Xing, Z., Chen, N., Pei, P., Yang, K. G., Wang, K., et al. (2024) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202300898 · Cited by 13 · see citing works
Polyphenols, Promising Therapeutics for Inflammatory Diseases?
Menaa, F., Badole, S. L., Menaa, B., Menaa, A., & Bodhankar, S. L. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-397156-2.00031-4 · Cited by 10 · see citing works
New insights on effects of a dietary supplement on oxidative and nitrosative stress in humans
Nemzer, B. V., Fink, N., & Fink, B. (2014) · Food Science & Nutrition · doi:10.1002/fsn3.178 · Cited by 10 · see citing works
Quercetin-Induced Enhancement of Nasal Epithelial Cells’ Ability to Produce Clara Cell 10-kD Protein In Vitro and In Vivo
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Suppressive activity of fexofenadine hydrochloride on nitric oxide production in-vitro and in-vivo
Asano, K., Kanai, K., Furuta, A., Furuya, A., Suzaki, H., & Hisamitsu, T. (2007) · Journal of Pharmacy and Pharmacology · doi:10.1211/jpp.59.10.0009 · Cited by 7 · see citing works
“Experimental evidence clearly show that administration of LPS to laboratory animals increases the activity of iNOS in cells and tissues, including macrophages and lung tissue, to produce NO (Wadsworth & Koop 2001).”
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“The overproduction and metabolites of nitric oxide (NO) have been implicated in the development of pathologies although it is extremely important to defend the body [25].”
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Sunkaria, A., Yadav, A., Sharma, S. K., & Sandhir, R. (2017) · Wiley eBooks · doi:10.1002/9781119155195.ch27 · Cited by 4 · see citing works
Effects of Indole-3-Carbinol and Flavonoids Administered Separately and in Combination on Nitric Oxide Production and iNOS Expression in Rats
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Ginkgo biloba extract (egb 761): inhibitory effect on nitric oxide production in the macrophage cell line raw 264.7
Kobuchi, H., Droy-Lefaix, M. T., Christen, Y., & Packer, L. (1997) · Biochemical Pharmacology · doi:10.1016/s0006-2952(96)00873-8 · Cited by 154 · see citing works
Effects of Ginkgo biloba extract (EGb 761) and quercetin on lipopolysaccharide-induced signaling pathways involved in the release of tumor necrosis factor-α 1 1Abbreviations: EGb 761, Ginkgo biloba extract; LPS, lipopolysaccharide; ROIs, reactive oxygen intermediates; TNF, tumor necrosis factor; IL, interleukin; COX, cyclooxygenase; iNOS, inducible nitric oxide synthase; TLR, Toll-like receptor; LBP, lipid binding protein; NF-κB, nuclear factor-κB; IKK, IκB kinase; AP-1, activator protein 1; ATF, activating transcription factor; CRE, cyclic AMP response element; CREB, cyclic AMP binding protein; C/EBP, CCAAT/enhancer binding protein; ARE, AU-rich element; -UTR, untranslated region; MAPK, mitogen-activated protein kinase; ERK, extracellular signal-related kinase; MEKK, MAPK/ERK kinase kinase; MEK, MAPK/ERK kinase; JNK/SAPK, Jun N terminal kinase/stress-activated protein kinase; EMSA, electrophoretic mobility shift assay; DTT, dithiothreitol; PMSF, phenylmethylsulfonyl fluoride; and ECL, enhanced chemiluminescence.
Wadsworth, T. L., McDonald, T. L., & Koop, D. R. (2001) · Biochemical Pharmacology · doi:10.1016/s0006-2952(01)00734-1 · Cited by 145 · see citing works
Preventive Effect of Ginkgo biloba Extract (GBB) on the Lipopolysaccharide-Induced Expressions of Inducible Nitric Oxide Synthase and Cyclooxygenase-2 via Suppression of Nuclear Factor-.KAPPA.B in RAW 264.7 Cells
Park, Y.-M., Won, J., Yun, K., Ryu, J.-H., Han, Y.-N., Choi, S.-K., & Lee, K. (2006) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.29.985 · Cited by 83 · see citing works
The inhibitory action of quercetin on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophage cells
Mu, M. M., Chakravortty, D., Sugiyama, T., Koide, N., Takahashi, K., Mori, I., Yoshida, T., & Yokochi, T. (2001) · Journal of Endotoxin Research · doi:10.1177/09680519010070060601 · Cited by 99 · see citing works
Immunomodulation of Inflammatory Markers in Activated Macrophages by Leaf Extracts of Gingko Biloba
Mir, M. A., & Al-Baradie, R. S. (2015) · Advances in Neuroimmune Biology · doi:10.3233/nib-150103 · Cited by 13 · see citing works

Authors: Wadsworth, T. L., & Koop, D. R.
Affiliations: Oregon Health & Science University (US)
Corresponding author: Koop, Dennis R
Venue: Chemico-Biological Interactions
Publisher: Elsevier BV
Published: 2001-07
Volume: 137
Issue: 1
Pages: 43-58
ISSN: 0009-2797 (ISSN-L)
DOI: 10.1016/s0009-2797(01)00208-3
OpenAlex: W2035027020
Cited by: 116
References: 62
Citations by year: 2025: 1 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 4 · 2019: 3 · 2018: 2 · 2017: 4 · 2016: 2 · 2015: 6 · 2014: 3 · 2013: 7 · 2012: 5
FWCI: 19.61
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Chemico-Biological Interactions (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute on Alcohol Abuse and Alcoholism (AA 08608)
Topics: Health Sciences › Medicine › Complementary and alternative medicine › Ginkgo biloba and Cashew Applications
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Health Sciences › Medicine › Pharmacology › Flavonoids in Medical Research
Keywords: Ginkgo biloba extract EGb 761, quercetin, lipopolysaccharide, nitric oxide, inducible nitric oxide synthase, macrophages, RAW 264.7 macrophages, p38 MAPK, NF-κB, AP-1, SAPK/JNK, flavonoids, anti-inflammatory activity, signal transduction
MeSH terms: Ginkgo Extract, Animals, Cells, Cultured, Dose-Response Relationship, Drug, Enzyme Inhibitors, Imidazoles, Lipopolysaccharides, Macrophages, Male, Mice, Inbred C57BL, Nitric Oxide, Nitroprusside, Plant Extracts, Pyridines, Quercetin, Tumor Necrosis Factor-alpha, Free Radical Scavengers, Nitric Oxide Synthase, Nitric Oxide Donors, Ginkgo biloba, Mice, Nitric Oxide Synthase Type II

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Effects of Ginkgo biloba extract (EGb 761) and quercetin on lipopolysaccharide-induced release of nitric oxide

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