Advertisement

Molecular & Cellular Toxicology

, Volume 11, Issue 2, pp 223–230 | Cite as

Protective effect of a novel herbmedicine, Hepad, on apoptosis of SH-SY5Y cells and a rat model of Parkinson’s disease

  • Seung Yeop Baek
  • Na Rae Lee
  • Da Hye Kim
  • Ayoung Gu
  • Seong Yeol Kim
  • Dae-Yong Song
  • Dong-Hee Kim
  • Hak Joo Choi
  • Byung-Jun ParkEmail author
  • In Sik KimEmail author
Original Paper

Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons in the substantia nigra pars compacta. In this study, we investigated the effects of a novel herb formula, Hepad, on PD. Dose-dependent treatment with 1-methyl-4-phenylpyridinium (MPP+) decreased the viability of SH-SY5Y cells, and Hepad inhibited the toxic effect of MPP+. Hepad blocked the production of reactive oxygen species (ROS) induced by MPP+ in SH-SY5Y cells, and suppressed the activation of caspase 9 and caspase 3 due to MPP+. A rat model of PD was generated by 6-hydroxydopamine (6-OHDA) injection into the left medial forebrain bundle (MFB) of SD rats. In D-amphetamine sulfate-induced rotational behavioral tests, Hepad administration attenuated circling behavior relative to the 6-OHDA-treated disease group. In addition, Hepad treatment significantly increased the tyrosine hydroxylase (TH)-positive cells in the substantia nigra pars compacta (SNpc) that had decreased in response to 6-OHDA treatment (P<0.05). OX-6 expression, which indicates the presence of microglial cells, decreased significantly after treatment of Hepad in contrast to the 6-OHDA-treated disease group (P<0.05). These results indicate that Hepad may be a useful neuroprotective material for the treatment of neurodegenerative disorders such as PD.

Keywords

Parkinson’s disease Hepad Reactive oxygen species Apoptosis 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    de Lau, L. M. and Breteler, M. M. Epidemiology of Par-kinson’s disease. Lancet Neurol 5:525–535 (2006).PubMedCrossRefGoogle Scholar
  2. 2.
    Zhao, Y. et al. GDNF-transfected macrophages pro-duce potent neuroprotective effects in Parkinson’s dis-ease mouse model. PLoS One 9:e106867 (2014).Google Scholar
  3. 3.
    Owen, A. D., Schapira, A. H., Jenner, P. & Marsden, C. D. Oxidative stress and Parkinson’s disease. Ann N Y Acad Sci 15:217–223 (1996).CrossRefGoogle Scholar
  4. 4.
    Kidd, P. M. Parkinson’s disease as multifactorial oxi-dative neurodegeneration: implications for integrative management. Altern Med Rev 5:502–529 (2000).PubMedGoogle Scholar
  5. 5.
    Jain, S., Wood, N. W. & Healy, D. G. Molecular genetic pathways in Parkinson’s disease: a review. Clin Sci (Lond) 109:355–364 (2005).CrossRefGoogle Scholar
  6. 6.
    Nicotra, A. & Parvez, S. Apoptotic molecules and MPTP-induced cell death. Neurotoxicol Teratol 24:599–605 (2002).PubMedCrossRefGoogle Scholar
  7. 7.
    Alberio, T., Lopiano, L. & Fasano, M. Cellular models to investigate biochemical pathways in Parkinson’s disease. FEBS J 279:1146–1155 (2012).PubMedCrossRefGoogle Scholar
  8. 8.
    Blandini, F. & Armentero, M. T. Animal models of par-kinson’s disease. FEBS J 279:1156–1166 (2012).PubMedCrossRefGoogle Scholar
  9. 9.
    Chotibut, T., Apple, D. M., Jefferis, R. & Salvatore, M. F. Dopamine transporter loss in 6-OHDA Parkinson’s model is unmet by parallel reduction in dopamine up-take. PLoS One 7:e52322 (2012).Google Scholar
  10. 10.
    Connolly, B. S. & Lang, A. E. Pharmacological treat-ment of Parkinson disease: a review. JAMA 311:1670–1683 (2014).PubMedCrossRefGoogle Scholar
  11. 11.
    Shulman, L. M., Taback, R. L., Bean, J. & Weiner, W. J. Comorbidity of the nonmotor symptoms of Parkinson’s disease. Mov Disord 16:507–510 (2001).PubMedCrossRefGoogle Scholar
  12. 12.
    Li, X. Z., Zhang, S. N., Liu, S. M. & Lu, F. Recent ad-vances in herbal medicines treating Parkinson’s disease. Fitoterapia 84:273–285 (2013).PubMedCrossRefGoogle Scholar
  13. 13.
    Adams, J. D., Klaidman, L. K. & Leung, A. C. MPP+ and MPDP+ induced oxygen radical formation with mitochondrial enzymes. Free Radic Biol Med 15:181–186 (1993).PubMedCrossRefGoogle Scholar
  14. 14.
    Lee, B. et al. Protective effects of methanol extract of Acori graminei rhizoma and Uncariae Ramulus et Un-cus on ischemia-induced neuronal death and cognitive impairments in the rat. Life Sci 74:435–450 (2003).PubMedCrossRefGoogle Scholar
  15. 15.
    Kim, J. H. et al. Effects of methanol extract of Uncari-ae Ramulus et Uncus on ibotenic acid-induced amnesia in the rat. J Pharmacol Sci 96:314–323 (2004).PubMedCrossRefGoogle Scholar
  16. 16.
    Hiratsuka, T. et al. Yokukansan inhibits neuronal death during ER stress by regulating the unfolded protein re-sponse. PLoS One 5:e13280 (2010).Google Scholar
  17. 17.
    Hirsch, E. C. & Hunot, S. Neuroinflammation in Par-kinson’s disease: a target for neuroprotection? Lancet Neurol 8:382–397 (2009).PubMedCrossRefGoogle Scholar
  18. 18.
    Hirsch, E. C., Vyas, S. & Hunot, S. Neuroinflammation in Parkinson’s disease. Parkinsonism Relat Disord 18 Suppl 1:S210-S212 (2012).Google Scholar
  19. 19.
    Kim, J., Park, C. S., Lim, Y. & Kim, H. S. Paeonia ja-ponica, Houttuynia cordata, and Aster scaber water extracts induce nitric oxide and cytokine production by lipopolysaccharide-activated macrophages. J Med Food 12:365–373 (2009).PubMedCrossRefGoogle Scholar
  20. 20.
    Chen, G. et al. Er-Miao-San, a traditional herbal for-mula containing Rhizoma Atractylodis and Cortex Phel-lodendri inhibits inflammatory mediators in LPS-stim-ulated RAW264.7 macrophages through inhibition of NF-kB pathway and MAPKs activation. J Ethnophar-macol 154:711–718 (2014).CrossRefGoogle Scholar
  21. 21.
    Jeong, J. W. et al. Ethanol extract of Poria cocos redu-ces the production of inflammatory mediators by sup-pressing the NF-kappaB signaling pathway in lipopoly-saccharide-stimulated RAW 264.7 macrophages. BMC Complement Altern Med 14:101 (2014).PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Lu, Y. T., Kuan, Y. C., Chang, H. H. & Sheu, F. Molec-ular cloning of a Poria cocos protein that activates Th1 immune response and allays Th2 cytokine and IgE pro-duction in a murine atopic dermatitis model. J Agric Food Chem 62:2861–2871 (2014).PubMedCrossRefGoogle Scholar
  23. 23.
    Dauer, W. & Przedborski, S. Parkinson’s disease: mech anisms and models. Neuron 39:889–909 (2003).PubMedCrossRefGoogle Scholar
  24. 24.
    Kim, S. W., Ko, H. S., Dawson, V. L. & Dawson, T. M. Recent advances in our understanding of Parkinson’s disease. Drug Discovery Today: Disease Mechanisms 2: 427–433 (2005).CrossRefGoogle Scholar
  25. 25.
    Zhang, Z. G. et al. Astragaloside IV prevents MPP+-induced SH-SY5Y cell death via the inhibition of Bax-mediated pathways and ROS production. Mol Cell Biochem 364: 209–216 (2012).PubMedCrossRefGoogle Scholar
  26. 26.
    Tseng, Y. T., Chang, F. R. & Lo, Y. C. The Chinese herbal formula Liuwei dihuang protects dopaminergic neurons against Parkinson’s toxin through enhancing antioxidative defense and preventing apoptotic death. Phytomedicine 21:724–733 (2014).PubMedCrossRefGoogle Scholar
  27. 27.
    Doo, A. R. et al. Neuroprotective effects of an herbal medicine, Yi-Gan San on MPP+/MPTP-induced cyto-toxicity in vitro and in vivo. J Ethnopharmacol 131: 433–442 (2010).PubMedCrossRefGoogle Scholar
  28. 28.
    Bae, N. et al. The neuroprotective effect of modified Yeoldahanso-tang via autophagy enhancement in mod-els of Parkinson’s disease. J Ethnopharmacol 134:313–322 (2011)PubMedCrossRefGoogle Scholar

Copyright information

© The Korean Society of Toxicogenomics and Toxicoproteomics and Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Seung Yeop Baek
    • 1
  • Na Rae Lee
    • 2
  • Da Hye Kim
    • 1
  • Ayoung Gu
    • 1
  • Seong Yeol Kim
    • 1
  • Dae-Yong Song
    • 3
  • Dong-Hee Kim
    • 4
  • Hak Joo Choi
    • 4
  • Byung-Jun Park
    • 4
    • 5
    Email author
  • In Sik Kim
    • 1
    • 2
    Email author
  1. 1.Department of Senior Healthcare, BK21 plus program, Graduate SchoolEulji UniversityDaejeonKorea
  2. 2.Department of Biomedical Laboratory Science, School of MedicineEulji UniversityDaejeonKorea
  3. 3.Department of Anatomy and Neuroscience, School of MedicineEulji UniversityDaejeonKorea
  4. 4.Department of Pathology, College of Oriental MedicineDaejeon UniversityDaejeonKorea
  5. 5.Young Jin Korea Medical ClinicSun CheonKorea

Personalised recommendations