Journal of Physiology & Pathology in Korean Medicine (동의생리병리학회지)

The Physiological Society of Korean Medicine and The Society of Pathology in Korean Medicine (대한동의생리학회·한의병리학회)
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Neuroprotective Effect of Hepad S9-1 in MPP+-treated PC12 Cells

MPP+로 유도된 파킨슨병 세포 모델에서 Hepad S9-1의 신경세포 보호 효과

  • Seo-Hee Mok (Department of Pathology, College of Korean Medicine, Daejeon University) ;
  • Byung-Jun Park (Department of Pathology, College of Korean Medicine, Daejeon University) ;
  • In-Hwan Joo (Department of Pathology, College of Korean Medicine, Daejeon University) ;
  • Jong-Min Park (Department of Pathology, College of Korean Medicine, Daejeon University) ;
  • Dong-Hee Kim (Department of Pathology, College of Korean Medicine, Daejeon University)
  • 목서희 (대전대학교 한의과대학 병리학교실) ;
  • 박병준 (대전대학교 한의과대학 병리학교실) ;
  • 주인환 (대전대학교 한의과대학 병리학교실) ;
  • 박종민 (대전대학교 한의과대학 병리학교실) ;
  • 김동희 (대전대학교 한의과대학 병리학교실)
  • Received : 2023.03.30
  • Accepted : 2023.06.28
  • Published : 2023.08.25
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Abstract

Parkinson's disease is the second most common neurodegenerative disease. Levodopa has a good effect for a period of two to five years, but long-term use reduces the effectiveness of the drug and accompanies side effects. To date, there is no strategy that has been able of fundamental treatment of Parkinson's disease. We developed Hepad S9-1 composed of 5 herbal materials (Paeonia lactiflora Pallas, Uncaria sinensis Havil, Spatholobus suberectus Dunn, Panax ginseng C. A. Meyer, and Glycyrrhiza uralensis Fischer). This in vitro study was conducted to search a novel disease-modifying drug, observing the effect of Hepad S9-1, a plant derived compounds on the apoptotic process of PC12 cells which was induced by 1-methyl-4-phenylpyridinium (MPP+). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to determine the effect of MMP+ or Hepad S9-1 on cell viability in PC12 cells. In addition, we examined cell protective effect of Hepad S9-1 in MPP+-induced PC12 cells. And gene and protein expression level of various factors that regulate apoptosis were confirmed by real-time PCR and western blot analysis. As a result of the study, Hepad S9-1 significantly inhibited MPP+-induced neuronal cell death. Also, Hepad S9-1 inhibited apoptosis-inducing Bcl-2 associated X (Bax) gene and protein expression, cytochrome C protein expression, caspase-9, caspase-7, caspase-3 and poly ADP-ribose polymerase (PARP) activation. In addition, the neuroprotective ability was objectively confirmed by up-regulating the genes and proteins expression of B-cell lymphoma-2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl) that defend at apoptosis. Therefore, it seems that Hepad S9-1 can be additionally applied to the treatment of Parkinson's disease to suppress the progression of dopaminergic neuronal cell death.

Keywords

References

  1. Abbas MM, Xu Z, Tan LC. Epidemiology of Parkinson's disease-East versus West. Movement disorders clinical practice. 2018;5(1):14-28. https://doi.org/10.1002/mdc3.12568
  2. Raza C, Anjum R. Parkinson's disease: Mechanisms, translational models and management strategies. Life sciences. 2019;226:77-90. https://doi.org/10.1016/j.lfs.2019.03.057
  3. Tysnes O-B, Storstein A. Epidemiology of Parkinson's disease. Journal of neural transmission. 2017;124:901-5. https://doi.org/10.1007/s00702-017-1686-y
  4. Radhakrishnan DM, Goyal V. Parkinson's disease: A review. Neurology India. 2018;66(7):26.
  5. Duwa R, Jeong J-H, Yook S. Development of immunotherapy and nanoparticles-based strategies for the treatment of Parkinson's disease. Journal of Pharmaceutical Investigation. 2021;51:465-81. https://doi.org/10.1007/s40005-021-00521-3
  6. Li W-w. Botanical Therapeutics for Parkinson's Disease. Chinese journal of integrative medicine. 2020;26(6):405-11. https://doi.org/10.1007/s11655-020-3096-5
  7. pments in the treatment of Parkinson's Disease. F1000Research. 2020;9.
  8. Kalia LV, Kalia SK, Lang AE. Disease-modifying strategies for Parkinson's disease. Movement Disorders. 2015;30(11):1442-50. https://doi.org/10.1002/mds.26354
  9. Park S-m, Lee S-h, Yin C-s, Kang M-k, Chang D-i, Kang S-k, et al. Literature Review on Parkinson's disease in Oriental medicine. Journal of Acupuncture Research. 2004;21(1):202-10.
  10. Lim SY, Kim HR, Choi YS, Lee I. Review of Current Clinical Studies for Herbal Medicine of Parkinson's Disease in Traditional Chinese Medicine. Journal of Physiology & Pathology in Korean Medicine. 2016;30(5):327-37. https://doi.org/10.15188/kjopp.2016.10.30.5.327
  11. Zheng M, Liu C, Fan Y, Shi D, Jian W. Total glucosides of paeony (TGP) extracted from Radix Paeoniae Alba exerts neuroprotective effects in MPTP-induced experimental parkinsonism by regulating the cAMP/PKA/CREB signaling pathway. Journal of ethnopharmacology. 2019;245:112182.
  12. Shim JS, Kim HG, Ju MS, Choi JG, Jeong SY, Oh MS. Effects of the hook of Uncaria rhynchophylla on neurotoxicity in the 6-hydroxydopamine model of Parkinson's disease. Journal of Ethnopharmacology. 2009;126(2):361-5. https://doi.org/10.1016/j.jep.2009.08.023
  13. Park HR, Lee H, Lee J-J, Yim N-H, Gu M-J, Ma JY. Protective effects of spatholobi caulis extract on neuronal damage and focal ischemic stroke/reperfusion injury. Molecular Neurobiology. 2018;55:4650-66. https://doi.org/10.1007/s12035-017-0652-x
  14. Gonzalez-Burgos E, Fernandez-Moriano C, Gomez-Serranillos MP. Potential neuroprotective activity of Ginseng in Parkinson's disease: a review. Journal of Neuroimmune Pharmacology. 2015;10:14-29. https://doi.org/10.1007/s11481-014-9569-6
  15. Park CH, Kim JH, Choi SH, Shin YS, Lee SW, Cho EJ. Protective effects of Glycyrrhiza uralensis Radix extract and its active compounds on H2O2-induced apoptosis of C6 glial cells. Korean Journal of Medicinal Crop Science. 2017;25(5):315-21. https://doi.org/10.7783/KJMCS.2017.25.5.315
  16. De Lau LM, Breteler MM. Epidemiology of Parkinson's disease. The Lancet Neurology. 2006;5(6):525-35. https://doi.org/10.1016/S1474-4422(06)70471-9
  17. Davie CA. A review of Parkinson's disease. British medical bulletin. 2008;86(1):109-27. https://doi.org/10.1093/bmb/ldn013
  18. Monzon-Sandoval J, Poggiolini I, Ilmer T, Wade-Martins R, Webber C, Parkkinen L. Human-specific transcriptome of ventral and dorsal midbrain dopamine neurons. Annals of Neurology. 2020;87(6):853-68. https://doi.org/10.1002/ana.25719
  19. Jazvinscak Jembrek M, Orsolic N, Mandic L, Sadzak A, Segota S. Anti-oxidative, anti-inflammatory and anti-apoptotic effects of flavonols: targeting Nrf2, NF-κB and p53 pathways in neurodegeneration. Antioxidants. 2021;10(10):1628.
  20. Melamed E, Ziv I, Djaldetti R. Management of motor complications in advanced Parkinson's disease. Movement disorders: official journal of the Movement Disorder Society. 2007;22(S17):S379-S84. https://doi.org/10.1002/mds.21680
  21. Thanvi B, Lo N, Robinson T. Levodopa-induced dyskinesia in Parkinson's disease: clinical features, pathogenesis, prevention and treatment. Postgraduate medical journal. 2007;83(980):384-8. https://doi.org/10.1136/pgmj.2006.054759
  22. Yuan J, Yankner BA. Apoptosis in the nervous system. Nature. 2000;407(6805):802-9. https://doi.org/10.1038/35037739
  23. Qiao C, Zhang L-X, Sun X-Y, Ding J-H, Lu M, Hu G. Caspase-1 deficiency alleviates dopaminergic neuronal death via inhibiting caspase-7/AIF pathway in MPTP/p mouse model of Parkinson's disease. Molecular Neurobiology. 2017;54:4292-302. https://doi.org/10.1007/s12035-016-9980-5
  24. Okouchi M, Ekshyyan O, Maracine M, Aw TY. Neuronal apoptosis in neurodegeneration. Antioxidants & redox signaling. 2007;9(8):1059-96. https://doi.org/10.1089/ars.2007.1511
  25. Youle RJ, Strasser A. The BCL-2 protein family: opposing activities that mediate cell death. Nature reviews Molecular cell biology. 2008;9(1):47-59.
  26. Czabotar PE, Lessene G, Strasser A, Adams JM. Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nature reviews Molecular cell biology. 2014;15(1):49-63. https://doi.org/10.1038/nrm3722
  27. Kim T-H, Kim P-H, Jeon B-K, Yoon J-R, Woo W-H, Mun Y-J, et al. Effect of Anemarrhenae Rhizoma ethanol extract on apoptosis induction of HT-29 human colon cancer cells. The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology. 2011;24(1):16-24. https://doi.org/10.6114/JKOOD.2011.24.1.016
  28. Erekat NS. Apoptosis and its Role in Parkinson's Disease. Exon Publications. 2018:65-82.
  29. Akbar AN, Borthwick NJ, Wickremasinghe RG, Panayiotidis P, Pilling D, Bofill M, et al. Interleukin-2 receptor common γ-chain signaling cytokines regulate activated T cell apoptosis in response to growth factor withdrawal: Selective induction of anti-apoptotic (bcl-2, bcl-xL) but not pro-apoptotic (bax, bcl-xS) gene expression. European journal of immunology. 1996;26(2):294-9. https://doi.org/10.1002/eji.1830260204