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Neuro-protective effects of Ligustri Fructus by suppression of oxidative stress in mouse model of Parkinson’s disease

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Abstract

Parkinson’s disease (PD) is a progressive degenerative disorder of the central nervous system (CNS) that leads to impairment of motor skills and speech. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes damage to the dopaminergic (DA) neurons, and 1-4-Methyl-4-phenylpyridinium (MPP+) causes cell death in differentiated PC12 cells that is similar to the degeneration that occurs in PD. Moreover, MPTP treatment increases the activity of the microglia cells that produced reactive oxygen species (ROS). We recently reported that Ligustri Fructus (LF), a widely used traditional herbal medicine, increases cell viability in a yeast model of PD. In the present study, we examined the inhibitory effect of LF (0.01, 5, 10 ug) on the neurotoxicity of MPTP in mice and on the MPP + -induced cell death in differentiated PC12 cells. In vivo experiment, MPTP injection revealed a significant loss of DA neurons in the substantia nigra, while LF (100, 200 mg/ kg) treatment dramatically reversed DA neuron loss in immunohistochemistry assay for tyrosine hydroxylase (TH). Furthermore, LF attenuated the MPP + -induced cell death, decreased the generation of ROS, and activated glutathione peroxidase in PC12 cells. These results suggest that LF may be beneficial for the treatment of neurodegenerative diseases such as PD.

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References

  • Bao X, Wang Z, Fang J, Li X (2002) Structural features of an immunostimulating and antioxidant acidic polysaccharide from the seeds of Cuscuta chinensis. Planta Med 68:237–243. doi:10.1055/s-2002-23133

    Article  CAS  PubMed  Google Scholar 

  • Beal MF (2002) Oxidatively modified proteins in aging and disease. Free Radic Biol Med 32:797–803

    Article  CAS  PubMed  Google Scholar 

  • Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F (1973) Brain dopamine and the syndromes of Parkinson and Huntington. clinical, morphological and neurochemical correlations. J Neurol Sci 20:415–455

    Article  CAS  PubMed  Google Scholar 

  • Block ML, Zecca L, Hong JS (2007) Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci 8:57–69. doi:10.1038/nrn2038

    Article  CAS  PubMed  Google Scholar 

  • Chiueh CC, Krishna G, Tulsi P, Obata T, Lang K, Huang SJ, Murphy DL (1992) Intracranial microdialysis of salicylic acid to detect hydroxyl radical generation through dopamine autooxidation in the caudate nucleus: effects of MPP+. Free Radic Biol Med 13:581–583

    Article  CAS  PubMed  Google Scholar 

  • Choi DK et al (2005) Ablation of the inflammatory enzyme myeloperoxidase mitigates features of Parkinson’s disease in mice. J Neurosci 25:6594–6600. doi:10.1523/JNEUROSCI.0970-05.2005

    Article  CAS  PubMed  Google Scholar 

  • Chung YC et al (2011) Fluoxetine prevents MPTP-induced loss of dopaminergic neurons by inhibiting microglial activation. Neuropharmacology 60:963–974. doi:10.1016/j.neuropharm.2011.01.043S0028-3908(11)00054-2

    Article  CAS  PubMed  Google Scholar 

  • Dauer W, Przedborski S (2003) Parkinson’s disease: mechanisms and models. Neuron 39:889–909

    Article  CAS  PubMed  Google Scholar 

  • Dexter DT, Jenner P (2013) Parkinson disease: from pathology to molecular disease mechanisms. Free Radic Biol Med 62:132–144. doi:10.1016/j.freeradbiomed.2013.01.018

    Article  CAS  PubMed  Google Scholar 

  • Fahn S, Cohen G (1992) The oxidant stress hypothesis in Parkinson’s disease: evidence supporting it. Ann Neurol 32:804–812. doi:10.1002/ana.410320616

    Article  CAS  PubMed  Google Scholar 

  • Feng LR, Maguire-Zeiss KA (2010) Gene therapy in Parkinson’s disease: rationale and current status. CNS Drugs 24:177–192. doi:10.2165/11533740-000000000-000001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gao HM, Liu B, Zhang W, Hong JS (2003) Critical role of microglial NADPH oxidase-derived free radicals in the in vitro MPTP model of Parkinson’s disease. FASEB J 17:1954–1956. doi:10.1096/fj.03-0109

    CAS  PubMed  Google Scholar 

  • Gao L, Li C, Wang Z et al. (2014) Ligustri Lucidi Fructus as a traditional Chinese medicine: a review of its phytochemistry and pharmacology. Nat Prod Res:1-18 doi: 10.1080/14786419.2014.954114

  • Haleagrahara N, Ponnusamy K (2010) Neuroprotective effect of Centella asiatica extract (CAE) on experimentally induced parkinsonism in aged Sprague-Dawley rats. J Toxicol Sci 35:41–47

    Article  CAS  PubMed  Google Scholar 

  • Hirsch EC, Breidert T, Rousselet E, Hunot S, Hartmann A, Michel PP (2003) The role of glial reaction and inflammation in Parkinson’s disease. Ann N Y Acad Sci 991:214–228

    Article  CAS  PubMed  Google Scholar 

  • Kadota T et al (1996) Expression of dopamine transporter at the tips of growing neurites of PC12 cells. J Histochem Cytochem 44:989–996

    Article  CAS  PubMed  Google Scholar 

  • Koutsilieri E, Scheller C, Tribl F, Riederer P (2002) Degeneration of neuronal cells due to oxidative stress--microglial contribution Parkinsonism. Relat Disord 8:401–406

    Article  CAS  Google Scholar 

  • Lang AE, Lozano AM (1998) Parkinson’s disease. first of two parts. N Engl J Med 339:1044–1053. doi:10.1056/NEJM199810083391506

    Article  CAS  PubMed  Google Scholar 

  • Langston JW, Irwin I, Langston EB, Forno LS (1984) 1-Methyl-4-phenylpyridinium ion (MPP+): identification of a metabolite of MPTP, a toxin selective to the substantia nigra. Neurosci Lett 48:87–92

    Article  CAS  PubMed  Google Scholar 

  • Li X, Li Y, Chen J, Sun J, Sun X, Kang X (2010) Tetrahydroxystilbene glucoside attenuates MPP + -induced apoptosis in PC12 cells by inhibiting ROS generation and modulating JNK activation. Neurosci Lett 483:1–5. doi:10.1016/j.neulet.2010.07.027S0304-3940(10)00928-6

    Article  CAS  PubMed  Google Scholar 

  • Liberatore GT et al (1999) Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease. Nat Med 5:1403–1409. doi:10.1038/70978

    Article  CAS  PubMed  Google Scholar 

  • Liu JH, Ho SC, Lai TH, Liu TH, Chi PY, Wu RY (2003) Protective effects of Chinese herbs on D-galactose-induced oxidative damage. Methods Find Exp Clin Pharmacol 25:447–452

    Article  PubMed  Google Scholar 

  • McGeer PL, McGeer EG (2008) Glial reactions in Parkinson’s disease. Mov Disord 23:474–483. doi:10.1002/mds.21751

    Article  PubMed  Google Scholar 

  • Miller RL, James-Kracke M, Sun GY, Sun AY (2009) Oxidative and inflammatory pathways in Parkinson’s disease. Neurochem Res 34:55–65. doi:10.1007/s11064-008-9656-2

    Article  CAS  PubMed  Google Scholar 

  • Ogawa N (1997) Dopamine neurotransmission and treatments for Parkinson’s disease in the molecular biology era. Eur Neurol 38(Suppl 1):2–5

    Article  CAS  PubMed  Google Scholar 

  • Pereira CF, Oliveira CR (2000) Oxidative glutamate toxicity involves mitochondrial dysfunction and perturbation of intracellular Ca2+ homeostasis. Neurosci Res 37:227–236

    Article  CAS  PubMed  Google Scholar 

  • Qin DN, She BR, She YC, Wang JH (2000) Effects of flavonoids from Semen Cuscutae on the reproductive system in male rats. Asian J Androl 2:99–102

    CAS  PubMed  Google Scholar 

  • Riederer P, Wuketich S (1976) Time course of nigrostriatal degeneration in parkinson’s disease. a detailed study of influential factors in human brain amine analysis. J Neural Transm 38:277–301

    Article  CAS  PubMed  Google Scholar 

  • Santos CM (2012) New agents promote neuroprotection in Parkinson’s disease models. CNS Neurol Disord Drug Targets 11:410–418

    Article  CAS  PubMed  Google Scholar 

  • Sung SH, Kim ES, Lee KY, Lee MK, Kim YC (2006) A new neuroprotective compound of Ligustrum japonicum leaves. Planta Med 72:62–64. doi:10.1055/s-2005-873140

    Article  CAS  PubMed  Google Scholar 

  • Vitvitsky V, Thomas M, Ghorpade A, Gendelman HE, Banerjee R (2006) A functional transsulfuration pathway in the brain links to glutathione homeostasis. J Biol Chem 281:35785–35793. doi:10.1074/jbc.M602799200

    Article  CAS  PubMed  Google Scholar 

  • Wang SS, Chen JH, Liu XJ (1994) Preliminary study on pharmacologic action of Ligustrum japonicum. Zhongguo Zhong Xi Yi Jie He Za Zhi 14:670–672

    CAS  PubMed  Google Scholar 

  • Wang Z, Fang JN, Ge DL, Li XY (2000) Chemical characterization and immunological activities of an acidic polysaccharide isolated from the seeds of Cuscuta chinensis. Lam Acta Pharmacol Sin 21:1136–1140

    CAS  PubMed  Google Scholar 

  • Wang XM, Fu H, Liu GX (2001) Effect of wuzi yanzong pill and its disassembled prescription on mitochondrial DNA deletion, respiratory chain complexes and ATP synthesis in aged rats. Zhongguo Zhong Xi Yi Jie He Za Zhi 21:437–440

    CAS  PubMed  Google Scholar 

  • Wu DC, Teismann P, Tieu K, Vila M, Jackson-Lewis V, Ischiropoulos H, Przedborski S (2003) NADPH oxidase mediates oxidative stress in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson’s disease. Proc Natl Acad Sci U S A 100:6145–6150. doi:10.1073/pnas.0937239100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang HM, Shin HK, Kang YH, Kim JK (2009) Cuscuta chinensis extract promotes osteoblast differentiation and mineralization in human osteoblast-like MG-63 cells. J Med Food 12:85–92. doi:10.1089/jmf.2007.0665

    Article  CAS  PubMed  Google Scholar 

  • Zeevalk GD, Bernard LP, Albers DS, Mirochnitchenko O, Nicklas WJ, Sonsalla PK (1997) Energy stress-induced dopamine loss in glutathione peroxidase-overexpressing transgenic mice and in glutathione-depleted mesencephalic cultures. J Neurochem 68:426–429

    Article  CAS  PubMed  Google Scholar 

  • Zhang ZT, Cao XB, Xiong N, Wang HC, Huang JS, Sun SG, Wang T (2010) Morin exerts neuroprotective actions in Parkinson disease models in vitro and in vivo. Acta Pharmacol Sin 31:900–906. doi:10.1038/aps.2010.77

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang JF et al (2011) Aqueous extracts of Fructus Ligustri Lucidi enhance the sensitivity of human colorectal carcinoma DLD-1 cells to doxorubicin-induced apoptosis via Tbx3 suppression. Integr Cancer Ther 10:85–91. doi:10.1177/1534735410373921

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (Ministry of Education, Science, and Technology, MEST) (no. 2007-0054931).

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Authors and Affiliations

  1. Department of Physiology, College of Korean Medicine, Kyung Hee University, #1, Hoegi-dong, Dongdaemungu, Seoul, 130-701, Republic of Korea

    Minsook Ye, Minhwan Kim & Hyunsu Bae

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  1. Minsook Ye
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  2. Minhwan Kim
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  3. Hyunsu Bae
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Correspondence to Hyunsu Bae.

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The study was approved by the University of Kyung Hee Animal Care and Use Committee (KHUASP(SE)-11-010).

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Ye, M., Kim, M. & Bae, H. Neuro-protective effects of Ligustri Fructus by suppression of oxidative stress in mouse model of Parkinson’s disease. Orient Pharm Exp Med 16, 123–129 (2016). https://doi.org/10.1007/s13596-016-0223-0

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