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Thuja orientalis leaves extract protects dopaminergic neurons against MPTP-induced neurotoxicity via inhibiting inflammatory action

MPTP로 유도된 Parkinson's disease 동물 모델에서 항염증효과를 통한 측백엽의 도파민신경보호 효과

  • Park, Gunhyuk (Department of Life and Nanopharmaceutical Science, Graduates school, Kyung Hee University) ;
  • Kim, Hyo Geun (Department of Oriental Pharmaceutical Science, College of Pharmacy Kyung Hee University) ;
  • Ju, Mi Sun (Department of Oriental Pharmaceutical Science, College of Pharmacy Kyung Hee University) ;
  • Kim, Ae-Jung (The Graduate School of Alternative Medicine, Kyunggi University) ;
  • Oh, Myung Sook (Department of Life and Nanopharmaceutical Science, Graduates school, Kyung Hee University)
  • 박건혁 (경희대학교 일반대학원 나노의약생명과학과) ;
  • 김효근 (경희대학교 약학대학 한약학과) ;
  • 주미선 (경희대학교 약학대학 한약학과) ;
  • 김애정 (경기대학교 대체의학대학원) ;
  • 오명숙 (경희대학교 일반대학원 나노의약생명과학과)
  • Received : 2014.04.25
  • Accepted : 2014.05.14
  • Published : 2014.05.30

Abstract

Objectives : The aim of this study was to investigate the protective effect of extract of Thuja orientalis leaves (TOFE) against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity by inhibition of inflammation in in vitro and in vivo models of Parkinson's disease (PD). Methods : We evaluated the effect of TOFE against lipopolysaccharide (LPS)/1-methyl-4-phenylpyridinium ($MPP^+$) toxicity using nitric oxide (NO) assay, inducible NO synthase and cyclooxygenase 2 western blot, tyrosine hydroxylase and microglia activation immunohistochemistry (IHC) in BV2 cell, primary rat mesencephalic neurons, or C57BL/6 mice. We also evaluated the effect of TOFE in mice PD model induced by MPTP. C57BL/6 mice were treated with TOFE 50 mg/kg for 5 days and were injected intraperitoneally with four administrations of MPTP on the last day. We conducted behavioral tests and IHC analysis to see how TOFE affect MPTP-induced neuronal loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) and striatum (ST) of mice. To assess the anti-inflammation effects, we carried out glial fibrillary acidic protein and macrophage-1 antigen integrin alpha M in IHC in SNpc and ST of mice. Results : In an in vitro system, TOFE decreasesd NO generations in BV2 cells. TOFE protected dopaminergic cells against LPS or $MPP^+$-induced toxicity in primary mesencephalic dopaminergic neurons. In vivo system, TOFE at 50 mg/kg treated group showed improved motor deteriorations than the MPTP only treated group and TOFE significantly protected striatal dopaminergic damage from MPTP-induced neurotoxicity in mice. Moreover, TOFE inhibited activation of astrocyte and microglia in SNpc and ST of the mice. Conclusions : We concluded that TOFE showed anti-parkinsonian effect by protection of dopaminergic neurons against MPTP toxicity through anti-inflammatory actions.

Keywords

References

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