Skip to main content
Top
Published in: NeuroMolecular Medicine 4/2020

01-12-2020 | Original Paper

Galuteolin Inhibited Autophagy for Neuroprotection Against Transient Focal Cerebral Ischemia in Rats

Authors: Juxun Zhu, Liyun Wang, Jinping Zhang

Published in: NeuroMolecular Medicine | Issue 4/2020

Login to get access

Abstract

Galuteolin, a Chinese herbal medicine, purified from Lonicera Japonica. In this study, we aimed to investigate the neuroprotective effect of galuteolin against cerebral ischemia/reperfusion (I/R) injury. We administered galuteolin or galuteolin and rapamycin to rats which had middle cerebral artery occlusion/reperfusion (MCAO/R). A series of characterizations were carried out to monitor the outcomes of galuteolin in I/R rats regarding the infarct volumes, neurological deficits, and brain water, as well as its effect on neuroprotection and autophagy. It was found that galuteolin significantly reduced the infarct volume, brain water content, and the neurological deficits in a dose-dependent manner. Neuron damages were decreased in the hippocampal carotid artery 1 pyramidal layer by galuteolin. The expression levels of neuron-specific enolase (NSE) increased after galuteolin treatment. Galuteolin significantly decreased the expression levels of autophagy-related proteins. In addition, galuteolin decreased rapamycin-related neuron damages and activations of autophagy in I/R rats. Our data suggested that galuteolin can inhibit ischemic brain injuries through the regulation of autophagy-related indicators in I/R.
Literature
go back to reference Barger, G., & White, F. D. (1923). Galuteolin, a new glucoside from Galega officinalis. Biochemical Journal, 17(6), 836.PubMedPubMedCentral Barger, G., & White, F. D. (1923). Galuteolin, a new glucoside from Galega officinalis. Biochemical Journal, 17(6), 836.PubMedPubMedCentral
go back to reference Buckley, K. M., Hess, D. L., Sazonova, I. Y., Periyasamy-Thandavan, S., Barrett, J. R., Kirks, R., et al. (2014). Rapamycin up-regulation of autophagy reduces infarct size and improves outcomes in both permanent MCAL, and embolic MCAO, murine models of stroke. Experimental & Translational Stroke Medicine, 6, 8. https://doi.org/10.1186/2040-7378-6-8.CrossRef Buckley, K. M., Hess, D. L., Sazonova, I. Y., Periyasamy-Thandavan, S., Barrett, J. R., Kirks, R., et al. (2014). Rapamycin up-regulation of autophagy reduces infarct size and improves outcomes in both permanent MCAL, and embolic MCAO, murine models of stroke. Experimental & Translational Stroke Medicine, 6, 8. https://​doi.​org/​10.​1186/​2040-7378-6-8.CrossRef
go back to reference Burda, J., Matiašová, M., Gottlieb, M., Danielisova, V., Nemethova, M., Garcia, L., et al. (2005). Evidence for a role of second pathophysiological stress in prevention of delayed neuronal death in the hippocampal CA1 region. Neurochemical Research, 30(11), 1397–1405.PubMed Burda, J., Matiašová, M., Gottlieb, M., Danielisova, V., Nemethova, M., Garcia, L., et al. (2005). Evidence for a role of second pathophysiological stress in prevention of delayed neuronal death in the hippocampal CA1 region. Neurochemical Research, 30(11), 1397–1405.PubMed
go back to reference Cao, Z., Ding, Y., Ke, Z., Cao, L., Li, N., Ding, G., et al. (2016). Luteoloside acts as 3C protease inhibitor of enterovirus 71 in vitro. PLoS ONE, 11(2), e0148693.PubMedPubMedCentral Cao, Z., Ding, Y., Ke, Z., Cao, L., Li, N., Ding, G., et al. (2016). Luteoloside acts as 3C protease inhibitor of enterovirus 71 in vitro. PLoS ONE, 11(2), e0148693.PubMedPubMedCentral
go back to reference Carloni, S., Buonocore, G., & Balduini, W. (2008). Protective role of autophagy in neonatal hypoxia–ischemia induced brain injury. Neurobiology of Disease, 32(3), 329–339.PubMed Carloni, S., Buonocore, G., & Balduini, W. (2008). Protective role of autophagy in neonatal hypoxia–ischemia induced brain injury. Neurobiology of Disease, 32(3), 329–339.PubMed
go back to reference Chen, W., Sun, Y., Liu, K., & Sun, X. (2014). Autophagy: a double-edged sword for neuronal survival after cerebral ischemia. Neural Regeneration Research, 9(12), 1210.PubMedPubMedCentral Chen, W., Sun, Y., Liu, K., & Sun, X. (2014). Autophagy: a double-edged sword for neuronal survival after cerebral ischemia. Neural Regeneration Research, 9(12), 1210.PubMedPubMedCentral
go back to reference Fan, S.-H., Wang, Y.-Y., Lu, J., Zheng, Y.-L., Wu, D.-M., Li, M.-Q., et al. (2014). Luteoloside suppresses proliferation and metastasis of hepatocellular carcinoma cells by inhibition of NLRP3 inflammasome. PLoS ONE, 9(2), e89961.PubMedPubMedCentral Fan, S.-H., Wang, Y.-Y., Lu, J., Zheng, Y.-L., Wu, D.-M., Li, M.-Q., et al. (2014). Luteoloside suppresses proliferation and metastasis of hepatocellular carcinoma cells by inhibition of NLRP3 inflammasome. PLoS ONE, 9(2), e89961.PubMedPubMedCentral
go back to reference Galluzzi, L., Bravo-San Pedro, J. M., Blomgren, K., & Kroemer, G. (2016). Autophagy in acute brain injury. Nature Reviews Neuroscience, 17(8), 467.PubMed Galluzzi, L., Bravo-San Pedro, J. M., Blomgren, K., & Kroemer, G. (2016). Autophagy in acute brain injury. Nature Reviews Neuroscience, 17(8), 467.PubMed
go back to reference Gao, L., Jiang, T., Guo, J., Liu, Y., Cui, G., Gu, L., et al. (2012). Inhibition of autophagy contributes to ischemic postconditioning-induced neuroprotection against focal cerebral ischemia in rats. PLoS ONE, 7(9), e46092.PubMedPubMedCentral Gao, L., Jiang, T., Guo, J., Liu, Y., Cui, G., Gu, L., et al. (2012). Inhibition of autophagy contributes to ischemic postconditioning-induced neuroprotection against focal cerebral ischemia in rats. PLoS ONE, 7(9), e46092.PubMedPubMedCentral
go back to reference Huang, X.-P., Ding, H., Yang, X.-Q., Li, J.-X., Tang, B., Liu, X.-D., et al. (2017). Synergism and mechanism of Astragaloside IV combined with Ginsenoside Rg1 against autophagic injury of PC12 cells induced by oxygen glucose deprivation/reoxygenation. Biomedicine & Pharmacotherapy, 89, 124–134. Huang, X.-P., Ding, H., Yang, X.-Q., Li, J.-X., Tang, B., Liu, X.-D., et al. (2017). Synergism and mechanism of Astragaloside IV combined with Ginsenoside Rg1 against autophagic injury of PC12 cells induced by oxygen glucose deprivation/reoxygenation. Biomedicine & Pharmacotherapy, 89, 124–134.
go back to reference Jiang, W. W., Huang, B. S., Han, Y., Deng, L. H., & Wu, L. X. (2017). Sodium hydrosulfide attenuates cerebral ischemia/reperfusion injury by suppressing overactivated autophagy in rats. FEBS Open Bio, 7(11), 1686–1695.PubMedPubMedCentral Jiang, W. W., Huang, B. S., Han, Y., Deng, L. H., & Wu, L. X. (2017). Sodium hydrosulfide attenuates cerebral ischemia/reperfusion injury by suppressing overactivated autophagy in rats. FEBS Open Bio, 7(11), 1686–1695.PubMedPubMedCentral
go back to reference Lee, J.-C., Cho, J.-H., Kim, I. H., Ahn, J. H., Park, J. H., Cho, G.-S., et al. (2015). Ischemic preconditioning inhibits expression of Na+/H+ exchanger 1 (NHE1) in the gerbil hippocampal CA1 region after transient forebrain ischemia. Journal of the Neurological Sciences, 351(1–2), 146–153.PubMed Lee, J.-C., Cho, J.-H., Kim, I. H., Ahn, J. H., Park, J. H., Cho, G.-S., et al. (2015). Ischemic preconditioning inhibits expression of Na+/H+ exchanger 1 (NHE1) in the gerbil hippocampal CA1 region after transient forebrain ischemia. Journal of the Neurological Sciences, 351(1–2), 146–153.PubMed
go back to reference Li, M., Qu, Y. Z., Zhao, Z. W., Wu, S. X., Liu, Y. Y., Wei, X. Y., et al. (2012). Astragaloside IV protects against focal cerebral ischemia/reperfusion injury correlating to suppression of neutrophils adhesion-related molecules. Neurochemistry International, 60(5), 458–465.PubMed Li, M., Qu, Y. Z., Zhao, Z. W., Wu, S. X., Liu, Y. Y., Wei, X. Y., et al. (2012). Astragaloside IV protects against focal cerebral ischemia/reperfusion injury correlating to suppression of neutrophils adhesion-related molecules. Neurochemistry International, 60(5), 458–465.PubMed
go back to reference Li, Q., Tian, Z., Wang, M., Kou, J., Wang, C., Rong, X., et al. (2019). Luteoloside attenuates neuroinflammation in focal cerebral ischemia in rats via regulation of the PPARγ/Nrf2/NF-κB signaling pathway. International Immunopharmacology, 66, 309–316.PubMed Li, Q., Tian, Z., Wang, M., Kou, J., Wang, C., Rong, X., et al. (2019). Luteoloside attenuates neuroinflammation in focal cerebral ischemia in rats via regulation of the PPARγ/Nrf2/NF-κB signaling pathway. International Immunopharmacology, 66, 309–316.PubMed
go back to reference Liu, Y., & Levine, B. (2015). Autosis and autophagic cell death: the dark side of autophagy. Cell Death and Differentiation, 22(3), 367.PubMed Liu, Y., & Levine, B. (2015). Autosis and autophagic cell death: the dark side of autophagy. Cell Death and Differentiation, 22(3), 367.PubMed
go back to reference Longa, E. Z., Weinstein, P. R., Carlson, S., & Cummins, R. (1989). Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke, 20(1), 84–91. Longa, E. Z., Weinstein, P. R., Carlson, S., & Cummins, R. (1989). Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke, 20(1), 84–91.
go back to reference Lu, Q., Harris, V. A., Kumar, S., Mansour, H. M., & Black, S. M. (2015). Autophagy in neonatal hypoxia ischemic brain is associated with oxidative stress. Redox Biology, 6, 516–523.PubMedPubMedCentral Lu, Q., Harris, V. A., Kumar, S., Mansour, H. M., & Black, S. M. (2015). Autophagy in neonatal hypoxia ischemic brain is associated with oxidative stress. Redox Biology, 6, 516–523.PubMedPubMedCentral
go back to reference Nocjar, C., Alex, K. D., Sonneborn, A., Abbas, A. I., Roth, B. L., & Pehek, E. A. (2015). Serotonin-2C and-2a receptor co-expression on cells in the rat medial prefrontal cortex. Neuroscience, 297, 22–37.PubMedPubMedCentral Nocjar, C., Alex, K. D., Sonneborn, A., Abbas, A. I., Roth, B. L., & Pehek, E. A. (2015). Serotonin-2C and-2a receptor co-expression on cells in the rat medial prefrontal cortex. Neuroscience, 297, 22–37.PubMedPubMedCentral
go back to reference Rami, A., Langhagen, A., & Steiger, S. (2008). Focal cerebral ischemia induces upregulation of Beclin 1 and autophagy-like cell death. Neurobiology of Disease, 29(1), 132–141.PubMed Rami, A., Langhagen, A., & Steiger, S. (2008). Focal cerebral ischemia induces upregulation of Beclin 1 and autophagy-like cell death. Neurobiology of Disease, 29(1), 132–141.PubMed
go back to reference Rice, J. E., Vannucci, R. C., & Brierley, J. B. (1981). The influence of immaturity on hypoxic-ischemic brain damage in the rat. Annals of Neurology, 9(2), 131–141.PubMed Rice, J. E., Vannucci, R. C., & Brierley, J. B. (1981). The influence of immaturity on hypoxic-ischemic brain damage in the rat. Annals of Neurology, 9(2), 131–141.PubMed
go back to reference Song, F., Wei, C., Zhou, L., Qin, A., Yang, M., Tickner, J., et al. (2018). Luteoloside prevents lipopolysaccharide-induced osteolysis and suppresses RANKL-induced osteoclastogenesis through attenuating RANKL signaling cascades. Journal of Cellular Physiology, 233(2), 1723–1735.PubMed Song, F., Wei, C., Zhou, L., Qin, A., Yang, M., Tickner, J., et al. (2018). Luteoloside prevents lipopolysaccharide-induced osteolysis and suppresses RANKL-induced osteoclastogenesis through attenuating RANKL signaling cascades. Journal of Cellular Physiology, 233(2), 1723–1735.PubMed
go back to reference Tsai, T.-C., Tung, Y.-T., Kuo, Y.-H., Liao, J.-W., Tsai, H.-C., Chong, K.-Y., et al. (2015). Anti-inflammatory effects of Antrodia camphorata, a herbal medicine, in a mouse skin ischemia model. Journal of Ethnopharmacology, 159, 113–121.PubMed Tsai, T.-C., Tung, Y.-T., Kuo, Y.-H., Liao, J.-W., Tsai, H.-C., Chong, K.-Y., et al. (2015). Anti-inflammatory effects of Antrodia camphorata, a herbal medicine, in a mouse skin ischemia model. Journal of Ethnopharmacology, 159, 113–121.PubMed
go back to reference Vannucci, R. C. (1990). Experimental biology of cerebral hypoxia-ischemia: Relation to perinatal brain damage. Pediatric Research, 27(4), 317.PubMed Vannucci, R. C. (1990). Experimental biology of cerebral hypoxia-ischemia: Relation to perinatal brain damage. Pediatric Research, 27(4), 317.PubMed
go back to reference Wang, X., Yuan, T., Yin, N., Ma, X., Zhang, Z., Zhu, Z., et al. (2018). Luteoloside protects the uterus from Staphylococcus aureus-induced inflammation, apoptosis, and injury. Inflammation, 41(5), 1702–1716.PubMed Wang, X., Yuan, T., Yin, N., Ma, X., Zhang, Z., Zhu, Z., et al. (2018). Luteoloside protects the uterus from Staphylococcus aureus-induced inflammation, apoptosis, and injury. Inflammation, 41(5), 1702–1716.PubMed
go back to reference Xin, X.-Y., Pan, J., Wang, X.-Q., Ma, J.-F., Ding, J.-Q., Yang, G.-Y., et al. (2011). 2-Methoxyestradiol attenuates autophagy activation after global ischemia. Canadian Journal of Neurological Sciences, 38(4), 631–638.PubMed Xin, X.-Y., Pan, J., Wang, X.-Q., Ma, J.-F., Ding, J.-Q., Yang, G.-Y., et al. (2011). 2-Methoxyestradiol attenuates autophagy activation after global ischemia. Canadian Journal of Neurological Sciences, 38(4), 631–638.PubMed
go back to reference Xu, Y., Tian, Y., Tian, Y., Li, X., & Zhao, P. (2016). Autophagy activation involved in hypoxic-ischemic brain injury induces cognitive and memory impairment in neonatal rats. Journal of Neurochemistry, 139(5), 795–805.PubMed Xu, Y., Tian, Y., Tian, Y., Li, X., & Zhao, P. (2016). Autophagy activation involved in hypoxic-ischemic brain injury induces cognitive and memory impairment in neonatal rats. Journal of Neurochemistry, 139(5), 795–805.PubMed
go back to reference Xuejiang, W., Ichikawa, H., & Konishi, T. (2001). Antioxidant potential of Qizhu Tang, a Chinese Herbal Medicine, and the effect of cerebral oxidative damage after ischemia reperfusion in rats. Biological and Pharmaceutical Bulletin, 24(5), 558–563.PubMed Xuejiang, W., Ichikawa, H., & Konishi, T. (2001). Antioxidant potential of Qizhu Tang, a Chinese Herbal Medicine, and the effect of cerebral oxidative damage after ischemia reperfusion in rats. Biological and Pharmaceutical Bulletin, 24(5), 558–563.PubMed
go back to reference Xuejiang, W., Magara, T., & Konishi, T. (1999). Prevention and repair of cerebral ischemia-reperfusion injury by Chinese herbal medicine, shengmai san, in rats. Free Radical Research, 31(5), 449–455.PubMed Xuejiang, W., Magara, T., & Konishi, T. (1999). Prevention and repair of cerebral ischemia-reperfusion injury by Chinese herbal medicine, shengmai san, in rats. Free Radical Research, 31(5), 449–455.PubMed
go back to reference Zhang, X., Yan, H., Yuan, Y., Gao, J., Shen, Z., Cheng, Y., et al. (2013). Cerebral ischemia-reperfusion-induced autophagy protects against neuronal injury by mitochondrial clearance. Autophagy, 9(9), 1321–1333.PubMed Zhang, X., Yan, H., Yuan, Y., Gao, J., Shen, Z., Cheng, Y., et al. (2013). Cerebral ischemia-reperfusion-induced autophagy protects against neuronal injury by mitochondrial clearance. Autophagy, 9(9), 1321–1333.PubMed
Metadata
Title
Galuteolin Inhibited Autophagy for Neuroprotection Against Transient Focal Cerebral Ischemia in Rats
Authors
Juxun Zhu
Liyun Wang
Jinping Zhang
Publication date
01-12-2020
Publisher
Springer US
Published in
NeuroMolecular Medicine / Issue 4/2020
Print ISSN: 1535-1084
Electronic ISSN: 1559-1174
DOI
https://doi.org/10.1007/s12017-020-08606-2

Other articles of this Issue 4/2020

NeuroMolecular Medicine 4/2020 Go to the issue