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01-10-2021 | Mannitol | Original Article

Isorhamnetin Alleviates High Glucose-Aggravated Inflammatory Response and Apoptosis in Oxygen-Glucose Deprivation and Reoxygenation-Induced HT22 Hippocampal Neurons Through Akt/SIRT1/Nrf2/HO-1 Signaling Pathway

Authors: Yuqin Wu, Lin Fan, Yun Wang, Jing Ding, Rongfu Wang

Published in: Inflammation | Issue 5/2021

Abstract

This study is aimed at exploring the potential of isorhamnetin in protection against diabetes-exacerbated ischemia/reperfusion-induced brain injury and elucidating its action mechanism. After establishment of the model of high glucose (HG)-aggravated oxygen-glucose deprivation and reoxygenation (OGD/R), HT22 cell viability was detected by CCK-8. Lactate dehydrogenase (LDH) activity, casapase-3 activity, and oxidative stress-related markers in HT22 cells were detected by corresponding commercial kits. The apoptosis of HG-treated HT22 cells following OGD/R was observed with TUNEL staining. The level of pro-inflammatory cytokines was examined by ELISA. The expression of Akt/SIRT1/Nrf2/HO-1 signaling-related proteins was assayed by Western blot. The results showed that HG noticeably worsened the OGD/R-induced apoptosis of HT22 cells. Isorhamnetin relieved the HG-aggravated OGD/R-induced apoptosis, inflammatory response, and oxidative stress of HT22 cells. Isorhamnetin alleviated the HG-aggravated OGD/R injury in HT22 cells through Akt/SIRT1/Nrf2/HO-1 signaling pathway. Meanwhile, treatment with Akt inhibitor LY294002 reversed the protective effects of isorhamnetin against HG-aggravated OGD/R injury in HT22 cells. In a conclusion, Isorhamnetin alleviates HG-aggravated OGD/R in HT22 hippocampal neurons through Akt/SIRT1/Nrf2/HO-1 signaling pathway.

Tachibana, M., T. Ago, Y. Wakisaka, J. Kuroda, M. Shijo, Y. Yoshikawa, M. Komori, A. Nishimura, N. Makihara, K. Nakamura, and T. Kitazono. 2017. Early reperfusion after brain ischemia has beneficial effects beyond rescuing neurons. Stroke 48 (8): 2222–2230. https://doi.org/10.1161/STROKEAHA.117.016689.CrossRefPubMed

Yang, Z., C. Weian, H. Susu, and W. Hanmin. 2016. Protective effects of mangiferin on cerebral ischemia-reperfusion injury and its mechanisms. Eur J Pharmacol 771: 145–151. https://doi.org/10.1016/j.ejphar.2015.12.003.CrossRefPubMed

Salim, S. 2017. Oxidative stress and the central nervous system. J Pharmacol Exp Ther 360 (1): 201–205. https://doi.org/10.1124/jpet.116.237503.CrossRefPubMedPubMedCentral

Solberg, R., M. Longini, F. Proietti, S. Perrone, C. Felici, A. Porta, O.D. Saugstad, and G. Buonocore. 2017. DHA reduces oxidative stress after perinatal asphyxia: a study in newborn piglets. Neonatology 112 (1): 1–8. https://doi.org/10.1159/000454982.CrossRefPubMed

Torres-Cuevas, I., M. Corral-Debrinski, and P. Gressens. 2019. Brain oxidative damage in murine models of neonatal hypoxia/ischemia and reoxygenation. Free Radic Biol Med 142: 3–15. https://doi.org/10.1016/j.freeradbiomed.2019.06.011.CrossRefPubMed

Yang, Y.S., S.J. Son, J.H. Choi, and J.C. Rah. 2018. Synaptic transmission and excitability during hypoxia with inflammation and reoxygenation in hippocampal CA1 neurons. Neuropharmacology 138: 20–31. https://doi.org/10.1016/j.neuropharm.2018.05.011.CrossRefPubMed

Chen, L., J. Cao, D. Cao, M. Wang, H. Xiang, Y. Yang, T. Ying, and H. Cong. 2019. Protective effect of dexmedetomidine against diabetic hyperglycemia-exacerbated cerebral ischemia/reperfusion injury: An in vivo and in vitro study. Life Sci 235: 116553. https://doi.org/10.1016/j.lfs.2019.116553.CrossRefPubMed

Chen, R., B. Ovbiagele, and W. Feng. 2016. Diabetes and stroke: epidemiology, pathophysiology, pharmaceuticals and outcomes. Am J Med Sci 351 (4): 380–386. https://doi.org/10.1016/j.amjms.2016.01.011.CrossRefPubMedPubMedCentral

Liao, C.C., C.C. Shih, C.C. Yeh, Y.C. Chang, C.J. Hu, J.G. Lin, and T.L. Chen. 2015. Impact of diabetes on stroke risk and outcomes: two nationwide retrospective cohort studies. Medicine (Baltimore) 94 (52): e2282. https://doi.org/10.1097/MD.0000000000002282.CrossRefPubMedCentral

10.

Masrur, S., M. Cox, D.L. Bhatt, E.E. Smith, G. Ellrodt, G.C. Fonarow, and L. Schwamm. 2015. Association of acute and chronic hyperglycemia with acute ischemic stroke outcomes post-thrombolysis: findings from get with the guidelines-stroke. J Am Heart Assoc 4 (10): e002193. https://doi.org/10.1161/JAHA.115.002193.CrossRefPubMedPubMedCentral

11.

Abdal Dayem, A., H.Y. Choi, Y.B. Kim, and S.G. Cho. 2015. Antiviral effect of methylated flavonol isorhamnetin against influenza. PLoS One 10 (3): e0121610. https://doi.org/10.1371/journal.pone.0121610.CrossRefPubMed

12.

Gong, G., Y.Y. Guan, Z.L. Zhang, K. Rahman, S.J. Wang, S. Zhou, X. Luan, and H. Zhang. 2020. Isorhamnetin: a review of pharmacological effects. Biomed Pharmacother 128: 110301. https://doi.org/10.1016/j.biopha.2020.110301.CrossRefPubMed

13.

Xu, S.L., R.C. Choi, K.Y. Zhu, K.W. Leung, A.J. Guo, D. Bi, H. Xu, D.T. Lau, T.T. Dong, and K.W. Tsim. 2012. Isorhamnetin, a flavonol aglycone from Ginkgo biloba L., induces neuronal differentiation of cultured PC12 cells: potentiating the effect of nerve growth factor. Evid Based Complement Alternat Med 2012: 278273. https://doi.org/10.1155/2012/278273.CrossRefPubMedPubMedCentral

14.

Zhang, N., F. Pei, H. Wei, T. Zhang, C. Yang, G. Ma, and C. Yang. 2011. Isorhamnetin protects rat ventricular myocytes from ischemia and reperfusion injury. Exp Toxicol Pathol 63 (1-2): 33–38. https://doi.org/10.1016/j.etp.2009.09.005.CrossRefPubMed

15.

Huang, L., H. He, Z. Liu, D. Liu, D. Yin, and M. He. 2016. Protective effects of isorhamnetin on cardiomyocytes against anoxia/reoxygenation-induced injury is mediated by SIRT1. J Cardiovasc Pharmacol 67 (6): 526–537. https://doi.org/10.1097/FJC.0000000000000376.CrossRefPubMed

16.

Duan, J., J. Cui, H. Zheng, M. Xi, C. Guo, Y. Weng, Y. Yin, G. Wei, J. Cao, Y. Wang, A. Wen, and B. Qiao. 2019. Aralia taibaiensis protects against I/R-induced brain cell injury through the Akt/SIRT1/FOXO3a pathway. Oxid Med Cell Longev 2019: 7609765–7609718. https://doi.org/10.1155/2019/7609765.CrossRefPubMedPubMedCentral

17.

Diao, C., Z. Chen, T. Qiu, H. Liu, Y. Yang, X. Liu, J. Wu, and L. Wang. 2019. Inhibition of PRMT5 attenuates oxidative stress-induced pyroptosis via activation of the Nrf2/HO-1 signal pathway in a mouse model of renal ischemia-reperfusion injury. Oxid Med Cell Longev 2019: 2345658–2345618. https://doi.org/10.1155/2019/2345658.CrossRefPubMedPubMedCentral

18.

Ping, F.C., and L.C. Jenkins. 1978. Protection of the brain from hypoxia: a review. Can Anaesth Soc J 25 (6): 468–473. https://doi.org/10.1007/BF03007408.CrossRefPubMed

19.

Ramiro, J.I., and A. Kumar. 2015. Updates on management of anoxic brain injury after cardiac arrest. Mo Med 112 (2): 136–141.PubMedPubMedCentral

20.

Nagashima, T., S. Wu, M. Yamaguchi, and N. Tamaki. 1999. Reoxygenation injury of human brain capillary endothelial cells. Cell Mol Neurobiol 19 (1): 151–161. https://doi.org/10.1023/a:1006980911551.CrossRefPubMed

21.

Zhang, J., J. Chen, C. Fan, J. Li, J. Lin, T. Yang, and M. Fan. 2017. Alteration of spontaneous brain activity after hypoxia-reoxygenation: a resting-state fMRI study. High Alt Med Biol 18 (1): 20–26. https://doi.org/10.1089/ham.2016.0083.CrossRefPubMed

22.

Caplan, L.R. 1996. Diabetes and brain ischemia. Diabetes 45 (Suppl 3): S95–S97. https://doi.org/10.2337/diab.45.3.s95.CrossRefPubMed

23.

Cho, C.H., H. Jang, M. Lee, H. Kang, H.J. Heo, and D.O. Kim. 2017. Sea Buckthorn (Hippophae rhamnoides L.) leaf extracts protect neuronal PC-12 cells from oxidative stress. J Microbiol Biotechnol 27 (7): 1257–1265. https://doi.org/10.4014/jmb.1704.04033.CrossRef

24.

Zhang, S., Y. Qi, Y. Xu, X. Han, J. Peng, K. Liu, and C.K. Sun. 2013. Protective effect of flavonoid-rich extract from Rosa laevigata Michx on cerebral ischemia-reperfusion injury through suppression of apoptosis and inflammation. Neurochem Int 63 (5): 522–532. https://doi.org/10.1016/j.neuint.2013.08.008.CrossRefPubMed

25.

Nishimura, Y., M. Ueki, M. Imanishi, S. Tomita, M. Ueno, J. Morishita, and T. Nishiyama. 2017. Reoxygenation with 100% oxygen following hypoxia in mice causes apoptosis. Shock 48 (5): 590–594. https://doi.org/10.1097/SHK.0000000000000891.CrossRefPubMed

26.

Xu, Y., C. Tang, S. Tan, J. Duan, H. Tian, and Y. Yang. 2020. Cardioprotective effect of isorhamnetin against myocardial ischemia reperfusion (I/R) injury in isolated rat heart through attenuation of apoptosis. J Cell Mol Med 24 (11): 6253–6262. https://doi.org/10.1111/jcmm.15267.CrossRefPubMedPubMedCentral

27.

Zhao, J.J., J.Q. Song, S.Y. Pan, and K. Wang. 2016. Treatment with isorhamnetin protects the brain against ischemic injury in mice. Neurochem Res 41 (8): 1939–1948. https://doi.org/10.1007/s11064-016-1904-2.CrossRefPubMed

28.

Minutoli, L., D. Puzzolo, M. Rinaldi, N. Irrera, H. Marini, V. Arcoraci, A. Bitto, G. Crea, A. Pisani, F. Squadrito, V. Trichilo, D. Bruschetta, A. Micali, and D. Altavilla. 2016. ROS-mediated NLRP3 inflammasome activation in brain, heart, kidney, and testis ischemia/reperfusion injury. Oxid Med Cell Longev 2016: 2183026–2183010. https://doi.org/10.1155/2016/2183026.CrossRefPubMedPubMedCentral

29.

Coimbra-Costa, D., N. Alva, M. Duran, T. Carbonell, and R. Rama. 2017. Oxidative stress and apoptosis after acute respiratory hypoxia and reoxygenation in rat brain. Redox Biol 12: 216–225. https://doi.org/10.1016/j.redox.2017.02.014.CrossRefPubMedPubMedCentral

30.

Shi, S., S. Lei, C. Tang, K. Wang, and Z. Xia. 2019. Melatonin attenuates acute kidney ischemia/reperfusion injury in diabetic rats by activation of the SIRT1/Nrf2/HO-1 signaling pathway. Biosci Rep 39 (1). https://doi.org/10.1042/BSR20181614.

31.

Zhang, B., M. Zhai, B. Li, Z. Liu, K. Li, L. Jiang, M. Zhang, W. Yi, J. Yang, D. Yi, H. Liang, Z. Jin, W. Duan, and S. Yu. 2018. Honokiol ameliorates myocardial ischemia/reperfusion injury in type 1 diabetic rats by reducing oxidative stress and apoptosis through activating the SIRT1-Nrf2 signaling pathway. Oxid Med Cell Longev 2018: 3159801–3159816. https://doi.org/10.1155/2018/3159801.CrossRefPubMedPubMedCentral

32.

Zhao, T.T., T.L. Yang, L. Gong, and P. Wu. 2018. Isorhamnetin protects against hypoxia/reoxygenation-induced injure by attenuating apoptosis and oxidative stress in H9c2 cardiomyocytes. Gene 666: 92–99. https://doi.org/10.1016/j.gene.2018.05.009.CrossRefPubMed

Title: Isorhamnetin Alleviates High Glucose-Aggravated Inflammatory Response and Apoptosis in Oxygen-Glucose Deprivation and Reoxygenation-Induced HT22 Hippocampal Neurons Through Akt/SIRT1/Nrf2/HO-1 Signaling Pathway
Authors: Yuqin Wu
Lin Fan
Yun Wang
Jing Ding
Rongfu Wang
Publication date: 01-10-2021
Publisher: Springer US
Keyword: Mannitol
Published in: Inflammation / Issue 5/2021
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI: https://doi.org/10.1007/s10753-021-01476-1

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