DOI QR코드

DOI QR Code

1-Methoxylespeflorin G11 Protects HT22 Cells from Glutamate-Induced Cell Death through Inhibition of ROS Production and Apoptosis

  • Lee, Phil Jun (College of Pharmacy and Research Institute of Pharmaceutical Science and Technology, Ajou University) ;
  • Pham, Chau Ha (Biometrology Group, Korea Research Institute of Standards and Science (KRISS)) ;
  • Thuy, Nguyen Thi Thanh (College of Pharmacy and Research Institute of Drug Development, Chonnam National University) ;
  • Park, Hye-Jin (College of Pharmacy and Research Institute of Pharmaceutical Science and Technology, Ajou University) ;
  • Lee, Sung Hoon (College of Pharmacy, Chung-Ang University) ;
  • Yoo, Hee Min (Biometrology Group, Korea Research Institute of Standards and Science (KRISS)) ;
  • Cho, Namki (College of Pharmacy and Research Institute of Drug Development, Chonnam National University)
  • Received : 2020.11.23
  • Accepted : 2020.12.28
  • Published : 2021.02.28

Abstract

This study aimed to investigate the neuroprotective effects of 1-methoxylespeflorin G11 (MLG), a pterocarpan, against glutamate-induced neurotoxicity in neuronal HT22 hippocampal cells. The protective effects of MLG were evaluated using MTT assay and microscopic analysis. The extent of apoptosis was studied using flow cytometric analysis performed on the damaged cells probed with annexin V/propidium iodide. Moreover, mitochondrial reactive oxygen species (ROS) were assessed using flow cytometry through MitoSOXTM Red staining. To determine mitochondrial membrane potential, staining with tetramethylrhodamine and JC-1 was performed followed by flow cytometry. The results demonstrated that MLG attenuates glutamate-induced apoptosis in HT22 cells by inhibiting intracellular ROS generation and mitochondrial dysfunction. Additionally, MLG prevented glutamate-induced apoptotic pathway in HT22 cells through upregulation of Bcl-2 and downregulation of cleaved PARP-1, AIF, and phosphorylated MAPK cascades. In addition, MLG treatment induced HO-1 expression in HT22 cells. These results suggested that MLG exhibits neuroprotective effects against glutamate-induced neurotoxicity in neuronal HT22 cells by inhibiting oxidative stress and apoptosis.

Keywords

References

  1. Crous-Bou M, Minguillon C, Gramunt N, Molinuevo JL. 2017. Alzheimer's disease prevention: from risk factors to early intervention. Alzheimer's Res. Ther. 9: 71. https://doi.org/10.1186/s13195-017-0297-z
  2. Grodzicki W, Dziendzikowska K. 2020 The role of selected bioactive compounds in the prevention of Alzheimer's Disease. Antioxidants 9: 229. https://doi.org/10.3390/antiox9030229
  3. Woo Y, Lim JS, Oh J, Lee JS, Kim JS. 2020. Neuroprotective effects of Euonymus alatus extract on scopolamine-induced memory deficits in mice. Antioxidants 9: 449. https://doi.org/10.3390/antiox9050449
  4. Park CH, Song JH, Kim SN, Lee JH, Lee HJ, Kang KS, et al. 2019. Neuroprotective effects of tetrahydrocurcumin against glutamate-induced oxidative stress in hippocampal HT22 cells. Molecules 25: 144. https://doi.org/10.3390/molecules25010144
  5. Kim DH, Kim DW, Jung BH, Lee JH, Lee H, Hwang GS, et al. 2019. Ginsenoside Rb2 suppresses the glutamate-mediated oxidative stress and neuronal cell death in HT22 cells. J. Ginseng Res. 43: 326-334. https://doi.org/10.1016/j.jgr.2018.12.002
  6. Filosa S, Pecorelli A, D'Esposito M, Valacchi G, Hajek J. 2015. Exploring the possible link between MeCP2 and oxidative stress in rett syndrome. Free Radic. Biol. Med. 88: 81-90. https://doi.org/10.1016/j.freeradbiomed.2015.04.019
  7. Di Meo F, Cuciniello R, Margarucci S, Bergamo P, Petillo O, Peluso G, et al. 2020. Ginkgo biloba prevents oxidative stress-induced apoptosis blocking p53 activation in neuroblastoma cells. Antioxidants 9: 279. https://doi.org/10.3390/antiox9040279
  8. Yoo G, Park SJ, Lee TH, Yang H, Baek YS, Kim N, et al. 2015. Flavonoids isolated from Lespedeza cuneata G Don and their inhibitory effects on nitric oxide production in lipopolysaccharide-stimulated BV-2 microglia cells. Pharmacogn. Mag. 11: 651-656. https://doi.org/10.4103/0973-1296.160466
  9. Selvam C, Jordan BC, Prakash S, Mutisya D, Thilagavathi R. 2017. Pterocarpan scaffold: A natural lead molecule with diverse pharmacological properties. Eur. J. Med. Chem. 128: 219-236. https://doi.org/10.1016/j.ejmech.2017.01.023
  10. Xia W, Luo P, Hua P, Ding P, Li C, Xu J, et al. 2018. Discovery of a new pterocarpan-type antineuroinflammatory compound from Sophora tonkinensis through suppression of the TLR4/NFκB/MAPK signaling pathway with PU 1 as a potential target. ACS Chem. Neurosci. 10: 295-303. https://doi.org/10.1021/acschemneuro.8b00243
  11. Sun H, Lei YN, Deng W, Wang HM, Teng YO, Zhao HY, et al. 2016. First total synthesis and cytotoxicity of naturally occurring Lespedezol E1. Chem. Nat. Compd. 52: 896-898. https://doi.org/10.1007/s10600-016-1807-0
  12. Lee Y, Joo E, Kim NW. 2006. Polyphenol contents and physiological activity of the Lespedeza bicolor extracts. Korean J. Food Preserv. 13: 616-622.
  13. Thuy NTT, Lee JE, Yoo HM, Cho N. 2019. Antiproliferative pterocarpans and coumestans from Lespedeza bicolor. J. Nat. Prod. 82: 3025-3032. https://doi.org/10.1021/acs.jnatprod.9b00567
  14. Woo J, Han D, Park J, Kim SJ, Kim Y. 2015. In-depth characterization of the secretome of mouse CNS cell lines by LC-MS/MS without prefractionation. Proteomics 15: 3617-3622. https://doi.org/10.1002/pmic.201400623
  15. Park SY, Jung WJ, Kang JS, Kim CM, Park G, Choi YW. 2015. Neuroprotective effects of α-iso-cubebene against glutamate-induced damage in the HT22 hippocampal neuronal cell line. Int. J. Mol. Med. 35: 525-532. https://doi.org/10.3892/ijmm.2014.2031
  16. Woo HS, Kim DW, Curtis-Long MJ, Lee BW, Lee JH, Kim JY, et al. 2011. Potent inhibition of bacterial neuraminidase activity by pterocarpans isolated from the roots of Lespedeza bicolor. Bioorg. Med. Chem. Lett. 21: 6100-6103. https://doi.org/10.1016/j.bmcl.2011.08.046
  17. Lee PJ, Park HJ, Yoo HM, Cho N. 2019. Betulin protects HT-22 hippocampal cells against ER stress through induction of heme oxygenase-1 and inhibition of ROS production. Nat. Prod. Commun. 14: 1-7.
  18. Kamogashira T, Hayashi K, Fujimoto C, Iwasaki S, Yamasoba T. 2017. Functionally and morphologically damaged mitochondria observed in auditory cells under senescence-inducing stress. NPJ Aging Mech. Dis. 3: 2. https://doi.org/10.1038/s41514-017-0002-2
  19. Lee JK, Kim NJ. 2017. Recent advances in the inhibition of p38 MAPK as a potential strategy for the treatment of Alzheimer's disease. Molecules 22: 1287. https://doi.org/10.3390/molecules22081287
  20. Lee PJ, Park HJ, Cho N, Kim HP. 2018. Aquaporin 11-dependent inhibition of proliferation by deuterium oxide in activated hepatic stellate cells. Molecules 23: 3209. https://doi.org/10.3390/molecules23123209
  21. Lee PJ, Park HJ, Cho N, Kim HP. 2018. 35-Diethoxy-3'-hydroxyresveratrol (DEHR) ameliorates liver fibrosis via caveolin-1 activation in hepatic stellate cells and in a mouse model of bile duct ligation injury. Molecules 23: 2833. https://doi.org/10.3390/molecules23112833