Osthole, a natural coumarin improves cognitive impairments and BBB dysfunction after transient global brain ischemia in C57 BL/6J mice: Involvement of Nrf2 pathway
Abstract
Oxidative stress and blood-brain barrier (BBB) disruption play important roles in cerebral ischemic pathogenesis and may represent targets for treatment. Earlier studies have shown that osthole, a main active constituent isolated from Cnidium monnieri (L.) Cusson, could be considered as an attractive therapeutic agent in the treatment of ischemic stroke. However, the mechanism underlying the protective effect remains vague. In this study we aimed to investigate the effect of osthole on transient cerebral ischemia as well as its mechanism(s) in C57 BL/6 J mice. Mice were subjected to transient global cerebral ischemia induced by bilateral common carotid artery occlusion for 25 min. Behavioral test was performed at 4 days after ischemia, followed by assessment of neuronal loss in hippocampal CA1 region. Osthole significantly improved the cognitive ability and enhanced the survival of pyramidal neurons in the CA1 region of mice after lesion. Further studies showed that osthole attenuated the permeation of BBB, which may contribute to antioxidative effect by increasing the superoxide dismutase activity and decreasing the malondialdehyde level in model mice. Further studies revealed that osthole obviously up-regulated the protein levels of nuclear factor erythroid 2-related factor 2/heme oxygenase 1 in HT22 cells. In conclusion, our findings indicated that osthole exerts neuroprotective effects against global cerebral ischemia injury by reducing oxidative stress injury and reserving the disruption of BBB, which may be attributed to elevating the protein levels of Nrf2 and HO-1.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Phenolic and flavonoid contents, catechins, coumarin, resveratrol, quercetin, curcumin, ginkgolide, glycyrrhizin, monoterpenoid, and S-allylcysteine isolated from various medicinal plants have been identified to have the potency to prevent Alzheimer's disease.
“Phenolic and flavonoid contents [91], catechins [92], coumarin [93], resveratrol [94], quercetin [95]; curcumin [96], ginkgolide [97], glycyrrhizin [98], monoterpenoid [99], and S-allylcysteine [100] which isolated from various medicinal plants have been identified to have the potency to prevent AD.”
From Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation (2022) · cites this paper as [93]
Cites
The Blood-Brain Barrier in Health and Chronic Neurodegenerative Disorders
Zlokovic, B. V. (2008) · Neuron · doi:10.1016/j.neuron.2008.01.003 · Cited by 3,280 · see citing works
Blood–brain Barrier: Structural Components and Function Under Physiologic and Pathologic Conditions
Persidsky, Y., Ramirez, S. H., Haorah, J., & Kanmogne, G. D. (2006) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-006-9025-3 · Cited by 922 · see citing works
Yemişçi, M., Özdemir, Y., Vural, A., Can, A., Topalkara, K., & Dalkara, T. (2009) · Nature Medicine · doi:10.1038/nm.2022 · Cited by 780 · see citing works
Pathophysiology, treatment, and animal and cellular models of human ischemic stroke
Woodruff, T. M., Thundyil, J., Tang, S., Sobey, C. G., Taylor, S. M., & Arumugam, T. V. (2011) · Molecular Neurodegeneration · doi:10.1186/1750-1326-6-11 · Cited by 603 · see citing works
The Nrf2/ARE Pathway as a Potential Therapeutic Target in Neurodegenerative Disease
Calkins, M. J., Johnson, D. A., Townsend, J. A., Vargas, M. R., Dowell, J. A., Williamson, T. P., Kraft, A. D., Lee, J., Li, J., & Johnson, J. A. (2008) · Antioxidants and Redox Signaling · doi:10.1089/ars.2008.2242 · Cited by 440 · see citing works
Heme oxygenase-1 induction by NRF2 requires inactivation of the transcriptional repressor BACH1
Reichard, J. F., Motz, G. T., & Puga, A. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm638 · Cited by 393 · see citing works
Chan, P. H., 川瀬, 誠., Murakami, K., Chen, S. F., Li, Y., Calagui, B., Reola, L., Carlson, E. J., & Epstein, C. J. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-20-08292.1998 · Cited by 340 · see citing works
The Role of Monoamine Metabolism in Oxidative Glutamate Toxicity
Maher, P. A., & Davis, J. B. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-20-06394.1996 · Cited by 338 · see citing works
Neuronal oxidative stress in acute ischemic stroke: Sources and contribution to cell injury
Manzanero, S., Santro, T., & Arumugam, T. V. (2012) · Neurochemistry International · doi:10.1016/j.neuint.2012.11.009 · Cited by 330 · see citing works
Advances in the Vascular Pathophysiology of Ischemic Stroke
del Zoppo, G. J., & Hallenbeck, J. M. (2000) · Thrombosis Research · doi:10.1016/s0049-3848(00)00218-8 · Cited by 326 · see citing works
Yang, G., Kitagawa, K., Matsushita, K., Mabuchi, T., Yagita, Y., Yanagihara, T., & Matsumoto, M. (1997) · Brain Research · doi:10.1016/s0006-8993(96)01453-9 · Cited by 246 · see citing works
Blood Brain Barrier in Hypoxic-Ischemic Conditions
Kaur, C., & Ling, E. (2008) · Current Neurovascular Research · doi:10.2174/156720208783565645 · Cited by 245 · see citing works
De novo expression of Trpm4 initiates secondary hemorrhage in spinal cord injury
Gerzanich, V., Woo, S. K., Vennekens, R., et al. (2009) · Nature Medicine · doi:10.1038/nm.1899 · Cited by 224 · see citing works
Mechanism for the protective effect of resveratrol against oxidative stress-induced neuronal death
Fukui, M., Choi, H. J., & Zhu, B. T. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.06.002 · Cited by 197 · see citing works
Takasago, T., Peters, E. E., Graham, D. I., Masayasu, H., & Macrae, I. M. (1997) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0701426 · Cited by 161 · see citing works
New Therapeutic Targets in the Neurovascular Pathway in Alzheimer's Disease
Zloković, B. V. (2008) · Neurotherapeutics · doi:10.1016/j.nurt.2008.05.011 · Cited by 149 · see citing works
Fluorescence imaging of blood–brain barrier disruption
Hawkins, B. T., & Egleton, R. D. (2005) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2005.08.006 · Cited by 146 · see citing works
Blood–brain barrier and traumatic brain injury
Alves, J. L. (2013) · Journal of Neuroscience Research · doi:10.1002/jnr.23300 · Cited by 135 · see citing works
Elements of cerebral microvascular ischaemia
Petty, M. A., & Wettstein, J. G. (2001) · Brain Research Reviews · doi:10.1016/s0165-0173(01)00062-5 · Cited by 127 · see citing works
Wellons, J. C., Sheng, H., Laskowitz, D. T., Mackensen, G. B., Pearlstein, R. D., & Warner, D. S. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02216-2 · Cited by 115 · see citing works
Ji, H., Hu, J., Wang, Y., Chen, X., Zhou, R., & Chen, N. (2010) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2010.03.038 · Cited by 107 · see citing works
Self-citationLiu, W., Zhou, J., Qu, Y., Li, X., Lu, C., Xie, K., Sun, X., & Fei, Z. (2010) · Neurochemistry International · doi:10.1016/j.neuint.2010.05.011 · Cited by 99 · see citing works
Escartin, C., Won, S. J., Malgorn, C., Aurégan, G., Berman, A., Chen, P., Déglon, N., Johnson, J. A., Suh, S. W., & Swanson, R. A. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.6577-10.2011 · Cited by 96 · see citing works
Brain damage in a mouse model of global cerebral ischemia
Olsson, T., Wieloch, T., & Smith, M.-L. (2003) · Brain Research · doi:10.1016/s0006-8993(03)03014-2 · Cited by 87 · see citing works
Zehendner, C. M., Librizzi, L., Hedrich, J., Bauer, N., Angamo, E. A., de Curtis, M., & Luhmann, H. J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0082823 · Cited by 87 · see citing works
Kirisattayakul, W., Wattanathorn, J., Tong-un, T., et al. (2013) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2013/951415 · Cited by 84 · see citing works
Nakamura, T., Kodama, N., Arai, Y., et al. (2008) · Journal of Natural Medicines · doi:10.1007/s11418-008-0277-5 · Cited by 80 · see citing works
Lee, Y. S., Kang, Y. J., Kim, H. J., et al. (2006) · APOPTOSIS · doi:10.1007/s10495-006-7110-y · Cited by 80 · see citing works
Ha, Y. M., Kim, M. Y., Park, M. K., Lee, Y. S., Kim, Y. M., Kim, H. J., Lee, J. H., & Chang, K. C. (2011) · APOPTOSIS · doi:10.1007/s10495-011-0688-8 · Cited by 76 · see citing works
Vasorelaxation of rat thoracic aorta caused by osthole isolated from Angelica pubescens
Ko, F., Wu, T.-S., Liou, M.-J., et al. (1992) · European Journal of Pharmacology · doi:10.1016/0014-2999(92)90576-p · Cited by 75 · see citing works
Mansoorali, K. P., Prakash, T., Kotresha, D., et al. (2012) · Phytomedicine · doi:10.1016/j.phymed.2012.07.004 · Cited by 71 · see citing works
Chen, X., Pi, R., Zou, Y., et al. (2009) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2009.12.008 · Cited by 59 · see citing works
Self-citationBang, S. Y., Kim, J., Kim, H.-Y., et al. (2012) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2012.08.037 · Cited by 58 · see citing works
Effect of Follicular Fluid NO, MDA and GSH Levels on in vitro Fertilization Outcomes
Yalçınkaya, E., Çakıroğlu, Y., Döğer, E., et al. (2013) · Journal of the Turkish-German Gynecological Association · doi:10.5152/jtgga.2013.53323 · Cited by 57 · see citing works
Zhen, G., & Doré, S. (2007) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2007.06.029 · Cited by 52 · see citing works
Li, Y., Lü, P., Li, Y., Yang, L., Feng, H., Huang, Y., Zhang, D., Chen, J., & Zhu, D. (2012) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2012.11.056 · Cited by 45 · see citing works
Osthole improves acute lung injury in mice by up-regulating Nrf-2/thioredoxin 1
Chen, X., Zhang, B., Hou, S.-J., et al. (2013) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2013.04.014 · Cited by 35 · see citing works
Self-citationYamashima, T., Tonchev, A. B., & Borlongan, C. V. (2007) · Biotechnology Journal · doi:10.1002/biot.200600219 · Cited by 31 · see citing works
Alterations in mRNA expression of BACE1, cathepsin B, and glutaminyl cyclase in mice ischemic brain
Ye, J., Pi, R., Mao, X., Chen, X., Qin, J., Xu, S., & Liu, P. (2009) · Neuroreport · doi:10.1097/wnr.0b013e328332024a · Cited by 20 · see citing works
Self-citationBenquet, P., Gee, C. E., & Gerber, U. R. (2008) · médecine/sciences · doi:10.1051/medsci/2008242185 · Cited by 19 · see citing works
Weston, R. M., Jarrott, B., Ishizuka, Y., & Callaway, J. K. (2006) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0706918 · Cited by 18 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Sivandzade, F., Prasad, S., Bhalerao, A., & Cucullo, L. (2019) · Redox Biology · doi:10.1016/j.redox.2018.11.017 · Cited by 639 · see citing works
Sharifi-Rad, J., Rapposelli, S., Sestito, S., Herrera-Bravo, J., Arancibia-Diaz, A., Salazar, L. A., Yeskaliyeva, B., Beyatli, A., Leyva-Gómez, G., González-Contreras, C., et al. (2022) · Journal of Personalized Medicine · doi:10.3390/jpm12091515 · Cited by 125 · see citing works
“Phenolic and flavonoid contents [91], catechins [92], coumarin [93], resveratrol [94], quercetin [95]; curcumin [96], ginkgolide [97], glycyrrhizin [98], monoterpenoid [99], and S-allylcysteine [100] which isolated from various medicinal plants have been identified to have the potency to prevent AD.”
Background
- Authors
- Chen, Z., Mao, X., Liu, A., Gao, X., Chen, X., Ye, M., Ye, J., Liu, P., Xu, S., Liu, J., He, W., Lian, Q., & Pi, R.
- Affiliations
- Sun Yat-sen University (CN)
- Guangzhou University of Chinese Medicine (CN)
- Gannan Medical University (CN)
- Corresponding author
- Lian, QiShen
- Pi, RongBiao
- Venue
- Neurochemical Research
- Published
- 2014-11-26
- Volume
- 40
- Issue
- 1
- Pages
- 186-194
- ISSN
- 0364-3190 (ISSN-L)
- 1573-6903
- OpenAlex
- W2020663182
- Cited by
- 51
- References
- 42
- Citations by year
- 2026: 1 · 2024: 7 · 2023: 6 · 2022: 2 · 2021: 3 · 2020: 4 · 2019: 2 · 2018: 13 · 2017: 3 · 2016: 5 · 2015: 5
- FWCI
- 2.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neurochemical Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China
- Sun Yat-sen University
- Topics
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- osthole, coumarins, transient global cerebral ischemia, ischemic stroke, blood-brain barrier disruption, Nrf2, heme oxygenase-1, oxidative stress, neuroprotection, cognitive impairment, CA1 pyramidal neurons, Cnidium monnieri, superoxide dismutase, malondialdehyde, HT22 cells
- MeSH terms
- Animals, Blood-Brain Barrier, Cells, Cultured, Ischemic Attack, Transient, Coumarins, Hippocampus, Male, Malondialdehyde, Mice, Inbred C57BL, Superoxide Dismutase, Neuroprotective Agents, Nootropic Agents, Maze Learning, NF-E2-Related Factor 2, Mice, Heme Oxygenase-1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review