Neuroprotection by Genipin against Reactive Oxygen and Reactive Nitrogen Species-Mediated Injury in Organotypic Hippocampal Slice Cultures
Abstract
Genipin, the multipotent ingredient in Gardenia jasmenoides fruit extract (GFE), may be an effective candidate for treatment following stroke or traumatic brain injury (TBI). Secondary injury includes damage mediated by reactive oxygen species (ROS) and reactive nitrogen species (RNS), which can alter the biological function of key cellular structures and eventually lead to cell death. In this work, we studied the neuroprotective potential of genipin against damage stemming from ROS and RNS production in organotypic hippocampal slice cultures (OHSC), as well as its potential as a direct free radical scavenger. A 50 µM dose of genipin provided significant protection against tert-butyl hydroperoxide (tBHP), a damaging organic peroxide. This dosage of genipin significantly reduced cell death at 48 h compared to vehicle control (0.1% DMSO) when administered 0, 1, 6, and 24 h after addition of tBHP. Similarly, genipin significantly reduced cell death at 48 h when administered 0, 1, 2, and 6h after addition of rotenone, which generates reactive oxygen species via a more physiologically relevant mechanism. Furthermore, genipin significantly reduced both cell death and nitrite levels at 24 h caused by S-nitroso-N-acetylpenicillamine (SNAP), a direct nitric oxide (NO) donor, and successfully quenched 1,1-Diphenyl-2-picryl-hydrazyl (DPPH), a stable free radical, suggesting that genipin may act as a direct free radical scavenger. Our encouraging findings suggest that genipin should be tested in animal models of CNS injury with a significant component of ROS- and RNS-mediated damage, such as TBI and stroke, to assess its in vivo efficacy.
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Genipin protects neuronal cells against the cytotoxicity of Aβ, H2O2, and rotenone by preventing ROS/RNS-induced damage.
“Genipin has also displayed the ability to protect neuronal cells against the cytotoxicity of Aβ, H2O2 and rotenone by preventing widespread damage induced by the increase of ROS and RNS production (Yamazaki et al., 2001; Hughes et al., 2014).”
From Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes (2022) · cites this paper as Hughes et al., 2014
Cites
A simple method for organotypic cultures of nervous tissue
Stoppini, L., Buchs, P., & Muller, D. (1991) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(91)90128-m · Cited by 3,097 · see citing works
DPPH antioxidant assay revisited
Sharma, O. P., & Bhat, T. K. (2008) · Food Chemistry · doi:10.1016/j.foodchem.2008.08.008 · Cited by 1,974 · see citing works
Vitamin C as an Antioxidant: Evaluation of Its Role in Disease Prevention
Padayatty, S. J., Katz, A., Wang, Y., Eck, P., Kwon, O., Lee, J.-H., Chen, S., Corpe, C., Dutta, A., Dutta, S. K., et al. (2003) · Journal of the American College of Nutrition · doi:10.1080/07315724.2003.10719272 · Cited by 1,949 · see citing works
Free Radical Pathways in CNS Injury
LEWÉN, A., MATZ, P., & CHAN, P. H. (2000) · Journal of Neurotrauma · doi:10.1089/neu.2000.17.871 · Cited by 759 · see citing works
Determination of nitrite/nitrate in human biological material by the simple Griess reaction
Guevara, I., Iwanejko, J., Dembinska-Kiec, A., Pankiewicz, J. E., Wanat, A., Anna, P., Leszczynska-Golabek, I., Bartuś, S., Malczewska-Malec, M., & Szczudlik, A. (1998) · Clinica Chimica Acta · doi:10.1016/s0009-8981(98)00060-6 · Cited by 647 · see citing works
Antioxidant and pro-oxidant properties of ascorbic acid and gallic acid
Yen, G., Duh, P., & Tsai, H.-L. (2002) · Food Chemistry · doi:10.1016/s0308-8146(02)00145-0 · Cited by 621 · see citing works
Measurement of nitrate and nitrite in biological samples using nitrate reductase and Griess reaction
Granger, D. L., Taintor, R. R., Boockvar, K. S., & Hibbs, J. B. (1996) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(96)68016-1 · Cited by 511 · see citing works
Strategies to advance translational research into brain barriers
Neuwelt, E., Abbott, N. J., Abrey, L., Banks, W. A., Blakley, B., Davis, T., Engelhardt, B., Grammas, P., Nedergaard, M., Nutt, J., et al. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(07)70326-5 · Cited by 474 · see citing works
Heme and Iron Metabolism: Role in Cerebral Hemorrhage
Wagner, K. R., Sharp, F. R., Ardizzone, T. D., Lu, A., & Clark, J. F. (2003) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/01.wcb.0000073905.87928.6d · Cited by 457 · see citing works
Anti-inflammatory evaluation of gardenia extract, geniposide and genipin
Koo, H.-J., Lim, K.-H., Jung, H., et al. (2005) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2005.08.011 · Cited by 404 · see citing works
Singh, I. N., Sullivan, P. G., Deng, Y., Mbye, L. H., & Hall, E. D. (2006) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600297 · Cited by 367 · see citing works
Novel Chitosan-Based Films Cross-Linked by Genipin with Improved Physical Properties
Jin, J., Song, M., & Hourston, D. J. (2003) · Biomacromolecules · doi:10.1021/bm034286m · Cited by 361 · see citing works
Zhang, C., Parton, L. E., Ye, C. P., Krauss, S., Shen, R., Lin, C.-T., Porco, J. A. J., & Lowell, B. B. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.04.010 · Cited by 332 · see citing works
Antiinflammatory effects of genipin, an active principle of gardenia
Koo, H.-J., Song, Y. S., Kim, H.-J., Lee, Y.-H., Hong, S.-M., Kim, S., Kim, B.-C., Jin, C., Lim, C., & Park, E. (2004) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2004.05.031 · Cited by 311 · see citing works
The effect of cross-linking of chitosan microspheres with genipin on protein release
Yuan, Y., Chesnutt, B. M., Utturkar, G., et al. (2006) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2006.10.023 · Cited by 296 · see citing works
Enzymic Studies on the Animal and Intestinal Bacterial Metabolism of Geniposide.
Akao, T., Kobashi, K., & Aburada, M. (1994) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.17.1573 · Cited by 235 · see citing works
Alía, M., Ramos, S., Mateos, R., Bravo, L., & Goya, L. (2005) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.20061 · Cited by 229 · see citing works
SMITH, S. L., Andrus, P. K., Zhang, J., & Hall, E. D. (1994) · Journal of Neurotrauma · doi:10.1089/neu.1994.11.393 · Cited by 194 · see citing works
Nitric Oxide in Traumatic Brain Injury
Cherian, L., Hlatky, R., & Robertson, C. S. (2004) · Brain Pathology · doi:10.1111/j.1750-3639.2004.tb00053.x · Cited by 189 · see citing works
Lifshitz, J., Friberg, H., Neumar, R. W., Raghupathi, R., Welsh, F. A., Janmey, P. A., Saatman, K. E., Wieloch, T. W., Grady, M. S., & McIntosh, T. K. (2003) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/01.wcb.0000040581.43808.03 · Cited by 182 · see citing works
Antithrombotic Effect of Geniposide and Genipin in the Mouse Thrombosis Model
Suzuki, Y., Kondo, K., Ikeda, Y., et al. (2001) · Planta Medica · doi:10.1055/s-2001-18842 · Cited by 148 · see citing works
Oxidative Stress in Immature Brain after Traumatic Brain Injury
Bayır, H., Kochanek, P. M., & Kagan, V. E. (2006) · Developmental Neuroscience · doi:10.1159/000094168 · Cited by 138 · see citing works
Antioxidant and Pro-Oxidant Effects of Various Tea Extracts
Yen, G., Chen, H.-Y., & Peng, H.-H. (1997) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf9603994 · Cited by 126 · see citing works
Metabolism and pharmacokinetics of genipin and geniposide in rats
Hou, Y., Tsai, S. Y., Lai, P. Y., et al. (2008) · Food and Chemical Toxicology · doi:10.1016/j.fct.2008.04.033 · Cited by 120 · see citing works
Lee, J., Lee, D., & Jeong, C. (2009) · Food and Chemical Toxicology · doi:10.1016/j.fct.2009.01.037 · Cited by 106 · see citing works
Antioxidant and pro‐oxidant capacities of ITCs
Valgimigli, L., & Iori, R. (2009) · Environmental and Molecular Mutagenesis · doi:10.1002/em.20468 · Cited by 96 · see citing works
Prevention of the Neurotoxicity of the Amyloid Beta Protein by Genipin
YAMAZAKI, M., SAKURA, N., CHIBA, K., & MOHRI, T. (2001) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.24.1454 · Cited by 62 · see citing works
Jeon, W.-K., Hong, H.-Y., & Kim, B.-C. (2011) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2011.05.016 · Cited by 60 · see citing works
Neuroprotection and Traumatic Brain Injury
Faden, A. I. (2001) · Archives of Neurology · doi:10.1001/archneur.58.10.1553 · Cited by 60 · see citing works
Yamazaki, M., & Chiba, K. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.12.001 · Cited by 53 · see citing works
Wang, G., Wu, S., Rao, J.-J., Xu, W., Xu, W., Pang, J., Liu, Z.-Q., Wu, S., & Zhang, J. (2009) · Acta Pharmacologica Sinica · doi:10.1038/aps.2009.31 · Cited by 51 · see citing works
Qiu, W., Zhou, Y., Jiang, L., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0041391 · Cited by 46 · see citing works
Morrison, B., Pringle, A. K., McManus, T. E., Ellard, J. M., Bradley, M., Signorelli, F., Iannotti, F., & Sundström, L. (2002) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0704986 · Cited by 43 · see citing works
Self-citationTseng, T.-Y., & Tsai, T. (2004) · Analytica Chimica Acta · doi:10.1016/j.aca.2004.04.040 · Cited by 25 · see citing works
Antioxidant and pro-oxidant in vitro evaluation of water-soluble food-related botanical extracts
Dorman, H. J. D., & Hiltunen, R. (2011) · Food Chemistry · doi:10.1016/j.foodchem.2011.06.017 · Cited by 23 · see citing works
Ohkubo, T., Yamazaki, M., & Yoshida, A. (2004) · Eisei kagaku · doi:10.1248/jhs.50.193 · Cited by 21 · see citing works
Rigg, J. L., Elovic, E. P., & Greenwald, B. D. (2005) · Journal of Head Trauma Rehabilitation · doi:10.1097/00001199-200507000-00010 · Cited by 16 · see citing works
Xu, G., Pérez‐Pinzón, M. A., & Sick, T. J. (2003) · Neurotoxicity Research · doi:10.1007/bf03033163 · Cited by 10 · see citing works
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Ferroptosis as a p53-mediated activity during tumour suppression
Jiang, L., Kon, N., Li, T., Wang, S.-J., Su, T., Hibshoosh, H., Baer, R., & Gu, W. (2015) · Nature · doi:10.1038/nature14344 · Cited by 3,398 · see citing works
Piccialli, I., Tedeschi, V., Caputo, L., D’Errico, S., Ciccone, R., De Feo, V., Secondo, A., & Pannaccione, A. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.876614 · Cited by 73 · see citing works
- Authors
- Hughes, R. H., Silva, V. A., Ahmed, I., Shreiber, D. I., & Morrison, B.
- Affiliations
- Columbia University (US)
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Morrison, Barclay
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 1543
- Pages
- 308-314
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W1994631252
- Cited by
- 46
- References
- 38
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 5 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 4 · 2018: 4 · 2017: 6 · 2016: 3 · 2015: 7 · 2014: 3
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- Funders
- New Jersey Commission on Brain Injury Research (10-3215-BIR-E-0)
- Topics
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
- Keywords
- genipin, neuroprotection, reactive oxygen species, reactive nitrogen species, oxidative stress, nitric oxide, free radical scavenging, organotypic hippocampal slice cultures, tert-butyl hydroperoxide, rotenone, SNAP, DPPH, traumatic brain injury, stroke, secondary brain injury, Gardenia jasminoides
- MeSH terms
- Analysis of Variance, Animals, Animals, Newborn, Ascorbic Acid, Biphenyl Compounds, Dose-Response Relationship, Drug, Hippocampus, Insecticides, Organ Culture Techniques, Picrates, Rotenone, Time Factors, Cell Death, Reactive Oxygen Species, Neuroprotective Agents, Nitric Oxide Donors, Reactive Nitrogen Species, S-Nitroso-N-Acetylpenicillamine, Iridoids
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