Herbal Formula Science (대한한의학방제학회지)

The Korean Medicine Society for the Herbal Formula Study (대한한의학방제학회)
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Protective effects of Jinnoe-san, a novel herbal formula in experimental in vitro models of Parkinson's disease

파킨슨병의 세포모델에서 진뇌산(鎭腦散)의 보호효과

  • Han, Sangtae ((Brain) Donguibogam Korean Medicine) ;
  • Jeong, Ji Cheon (Department of Korean Internal Medicine, College of Korean Medicine, Dongguk University)
  • 한상태 ((브레인)동의보감한의원) ;
  • 정지천 (동국대학교 한의과대학 내과학교실)
  • Received : 2017.10.27
  • Accepted : 2017.11.10
  • Published : 2017.11.30
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Abstract

Objectives : Jinnoe-san (JNS) is a novel herbal formula consisting of five oriental medicinal herbs including Polygalae Radix, Prunellae Spica, Perillae Herba, Betulae Cortex, and Lonicerae Flos. In this study, we investigated the effects and molecular mechanism of JNS on Parkinson's disease in vitro model. Methods : The effects of JNS on 1-methyl-4-phenylpyridinium ($MPP^+$)-induced cell death in SH-SY5Y cells were evaluated with a cell viability assay, flow cytometry, and western blots analysis. The effects of JNS on lipopolysaccharide (LPS)-stimulated BV2 microglia were determined with a nitric oxide (NO) assay, enzyme linked immunosorbent assays, and western blots analysis. Result : $MPP^+$-induced cell death in SH-SY5Y cells was significantly reduced by JNS pre-treatment in a dose-dependent manner. JNS inhibited the production of reactive oxygen species, mitochondria dysfunction, and apoptosis induced by $MPP^+$ in SH-SY5Y cells. Furthermore, JNS significantly activated Akt and ERK in SH-SY5Y cells and the ability of JNS to prevent mitochondria dysfunction by $MPP^+$ was antagonized by pre-treatment of LY294002 and PD98059, an Akt and ERK inhibitor, respectively. In addition, JNS inhibited LPS-induced NO and $PGE_2$ production as well as iNOS expression and secretion of TNF-${\alpha}$, pro-inflammatory cytokines without affecting the cell viability. JNS also suppressed LPS-induced ERK activation. Conclusions : These results demonstrate that JNS has a protective effect on the dopaminergic neurons against $MPP^+$-induced neurotoxicity and anti-inflammatory effect on the LPS-stimulated microglia. These findings provide evidences for JNS to be considered as a new prescription for treating Parkinson's disease.

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References

  1. Dauer W, Przedborski S. Parkinson's disease: mechanisms and models. Neuron 2003;39: 889-909. https://doi.org/10.1016/S0896-6273(03)00568-3
  2. de Lau LM, Breteler MM. Epidemiology of Parkinson's disease. Lancet Neurol. 2006;5:525-35. https://doi.org/10.1016/S1474-4422(06)70471-9
  3. Pringsheim T, Jette N, Frolkis A, Steeves TD. The prevalence of Parkinson′s disease: a systematic review and meta-analysis. Mov Disord. 2014;29:1583-90. https://doi.org/10.1002/mds.25945
  4. Calabrese V, Cornelius C, Mancuso C, Lentile R, Stella AM, Butterfield DA. Redox homeostasis and cellular stress response in aging and neurodegeneration. Methods Mol Biol. 2010; 610:285-308.
  5. Yacoubian TA and Standaert DC. Targets for neuroprotection in Parkinson's disease. Biochim. Biophys. Acta. 2009;1792(7):676-87. https://doi.org/10.1016/j.bbadis.2008.09.009
  6. Przedborski S, Jackson-Lewis V, Djaldetti R, Liberatore G, Vila M, Vukosavic S, et al. The parkinsonian toxin MPTP: action and mechanism. Restor Neurol Neurosci. 2000;16:135-42.
  7. Chuenkova MV, Pereira MA. PDNF, a human parasite-derived mimic of neurotrophic factors, prevents caspase activation, free radical formation, and death of dopaminergic cells exposed to the Parkinsonism inducing neurotoxin MPP+. Brain Res Mol Brain Res. 2003;119:50-61. https://doi.org/10.1016/j.molbrainres.2003.08.012
  8. Jenner P. Oxidative stress in Parkinson's disease. Ann Neurol 2003; 53:S26-S38. https://doi.org/10.1002/ana.10483
  9. Ott M, Gogvadze V, Orrenius S, Zhivotovsky B. Mitochondria, oxidative stress and cell death. Apoptosis 2007;12:913-22. https://doi.org/10.1007/s10495-007-0756-2
  10. Storch A, Ludolph AC, Schwarz J. Dopamine transporter: involvement in selective dopaminergic neurotoxicity and degeneration. J Neural Transm 2004;111:1267-86. https://doi.org/10.1007/s00702-004-0203-2
  11. Lee CS, Kim YJ, Ko HH, Han ES. Modulation of 1-methyl-4-phenylpyridinium-induced mitochondrial dysfunction and cell death by KATP channel block. J Neural Transm 2007; 114:297-305. https://doi.org/10.1007/s00702-006-0594-3
  12. Amor S, Puentes F, Baker D, van der Valk P. Inflammation in neurodegenerative diseases. Immunology. 2010;129:154-69. https://doi.org/10.1111/j.1365-2567.2009.03225.x
  13. Arimoto T, Bing G: Up-regulation of inducible nitric oxide synthase in the substantia nigra by lipopolysaccharide causes microglial activation and neurodegeneration. Neurobiol Dis 2003; 12:35-45. https://doi.org/10.1016/S0969-9961(02)00017-7
  14. F. Gonzalez-Scarano, G. Baltuch. Microglia as mediators of inflammatory and degenerative diseases. Annual Review of Neuroscience. 1999; 22:219-40. https://doi.org/10.1146/annurev.neuro.22.1.219
  15. Depino AM, Earl C, Kaczmarczyk E, Ferrari C, Besedovsky H, del Rey A, Pitossi FJ, Oertel WH: Microglial activation with atypical proinflammatory cytokine expression in a rat model of Parkinson's disease. Eur J Neurosci 2003; 18;2731-42. https://doi.org/10.1111/j.1460-9568.2003.03014.x
  16. Kyriakis JM, Avruch J. Mammalian mitogenactivated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev. 2001;81(2):807-69. https://doi.org/10.1152/physrev.2001.81.2.807
  17. Lee DS, Choi HG, Li B, Kim KS, Kim SA, Chon SK et al. Neuroprotective effect of the acid hydrolysis fraction of the roots of Polygala tenuifolia. Korean J Orient Physiol Pathol 2011;25(4):628-34.
  18. Shin MK. Clinical Traditional Herbalogy. Seoul: Yeong Lim's Publisher. 2000:329-30, 383-4, 399-40, 411-2, 646-7.
  19. Kim YH. Herbalogy. Seoul:Hanol Publisher 2014:76
  20. Yang GH, Kim HW, Cho SJ, Kim SD, Yoon KH, Kim BY et al. Effects of Folium Perillae on cytokine productions in ischemic rats. Kor. J. Herbology. 2007;22(3):93-9.
  21. Kim Y, Yang SY, Oh YS, Lee JW, Lee YK, Park YC. Research trends of Lonicera japonica over the last 10 year. J Daejeon Orient Med. 2010;19:17-23.
  22. Xie HR, Hu LS, Li GY. SH-SY5Y human neuroblastoma cell line: in vitro cell model of dopaminergic neurons in Parkinson's disease. Chin Med J (Engl). 2010;123(8):1086-92.
  23. Lee HJ, Noh YH, Lee DY, Kim YS, Kim KY, Chung YH et al. Baicalein attenuates 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells. Eur J Cell Biol. 2005;84(11): 897-905. https://doi.org/10.1016/j.ejcb.2005.07.003
  24. Watabe M, Nakaki T. Rotenone induces apoptosis via activation of bad in human dopaminergic SH-SY5Y cells. J Pharmacol Exp Ther. 2004; 311(3):948-53. https://doi.org/10.1124/jpet.104.071381
  25. Fall CP, Bennett JP Jr. Characterization and time course of MPP+ -induced apoptosis in human SH-SY5Y neuroblastoma cells. J Neurosci Res. 1999;55(5):620-8. https://doi.org/10.1002/(SICI)1097-4547(19990301)55:5<620::AID-JNR9>3.0.CO;2-S
  26. Martinou JC and Youle RJ. Mitochondria in apoptosis: Bcl-2 family members and mitochondrial dynamics. Dev Cell 2011;21:92-101. https://doi.org/10.1016/j.devcel.2011.06.017
  27. Chai F, Truong-Tran AQ, Ho LH, Zalewski PD. Regulation of caspase activation and apoptosis by cellular zinc fluxes and zinc deprivation: A review. Immunol Cell Biol. 1999;77:272-8. https://doi.org/10.1046/j.1440-1711.1999.00825.x
  28. Song G, Ouyang G, Bao S. The activation of Akt/PKB signaling pathway and cell survival. J Cell Mol Med. 2005;9(1):59-71. https://doi.org/10.1111/j.1582-4934.2005.tb00337.x
  29. Chang L, Karin M. Mammalian MAP kinase signalling cascades. Nature 2001;410(6824): 37-40. https://doi.org/10.1038/35065000
  30. Jung YS, Jung HM, Seo UK. Neuroprotective effect of methanol extract of Phellodendri Cortex against 1-methyl-4-phenylpyridiniuminduced apoptosis in PC-12 cells. Korean J Orient Int Med. 2009;30(1):51-63.
  31. Bae KR, Doo AR, Kim SN, Park JY, Park HJ, Lee HJ et al. Neuroprotective effects of bee venom, which removes high molecular elements against MPP+-induced human neuroblastoma SH-SY5Y cell death. Korean J Orient Int Med. 2010;31(2):66-75.
  32. Woo C, You JY, Jang CY, Kim HR, Shin YJ, Moon AJ et al. Protective effects of Sosokmyoungtang against Parkinson's Model in human neuroblastoma SH-SY5Y cells. J Int Korean Med. 2014;35(3):298-308.
  33. Baek SY, Lee NR, Kim DH, Gu A, Kim SY, Song DY et al. Protective effect of a novel herbmedicine, Hepad, on apoptosis of SH-SY5Y cells and a rat model of Parkinson's disease. Mol Cell Toxicol. 2015;11(2):223-30. https://doi.org/10.1007/s13273-015-0021-7
  34. Chao CC, Hu S, Molitor TW, Shaskan EG, Peterson PK. Activated microglia mediate neuronal cell injury via a nitric oxide mechanism. J Immunol. 1992;149:2736-41.
  35. Kalinski P. Regulation of immune responses by prostaglandin E2. J Immunol. 2012;188(1):21-8. https://doi.org/10.4049/jimmunol.1101029
  36. Turini ME, DuBois RN. Cyclooxygenase-2: a therapeutic target. Annu Rev Med. 2002;53:35-57. https://doi.org/10.1146/annurev.med.53.082901.103952