Acacetin Protects Dopaminergic Cells against 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Neuroinflammation in Vitro and in Vivo

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  • Kim Hyo Geun
    Department of Oriental Pharmaceutical Science, College of Pharmacy and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University
  • Ju Mi Sun
    Department of Oriental Pharmaceutical Science, College of Pharmacy and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University
  • Ha Sang Keun
    Graduate School of East-West Medical Science, Kyung Hee University
  • Lee Hyangsook
    Studies of Translational Acupuncture Research (STAR), Acupuncture & Meridian Science Research Center (AMSRC), Kyung Hee University
  • Lee Hyejung
    Studies of Translational Acupuncture Research (STAR), Acupuncture & Meridian Science Research Center (AMSRC), Kyung Hee University
  • Kim Sun Yeou
    Graduate School of East-West Medical Science, Kyung Hee University College of Pharmacy, Gachon University
  • Oh Myung Sook
    Department of Oriental Pharmaceutical Science, College of Pharmacy and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University Department of Life and Nanopharmaceutical Sciences, Kyung Hee University

書誌事項

タイトル別名
  • Acacetin Protects Dopaminergic Cells against 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Neuroinflammation <i>in Vitro</i> and <i>in Vivo</i>
公開日
2012
資源種別
journal article
DOI
  • 10.1248/bpb.b12-00127
公開者
公益社団法人 日本薬学会

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説明

Acacetin (5,7-dihydroxy-4′-methoxyflavone), a constituent of flavone naturally present in plants, has anti-cancer and anti-inflammatory activities. Neuroinflammation is thought to be one of the major pathological mechanisms responsible for Parkinson’s disease (PD), and has been a primary target in the development of treatment for PD. In the present study, we evaluated the neuroprotective effect of acacetin in PD induced by 1-methyl-4-phenylpyridine (MPP+)/or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and examined the related pathways in vitro and in vivo. In primary mesencephalic culture, acacetin protected dopaminergic (DA) cells and inhibited production of inflammatory factors such as nitric oxide, prostaglandin E2, and tumor necrosis factor-α against MPP+-induced toxicity in a dose-dependent manner. Then, we confirmed the effect of acacetin (10 mg/kg/d for 3 d, per os (p.o.)) in a mouse model of PD induced by MPTP (30 mg/kg/d for 5 d, intraperitoneally (i.p.)). In the behavioral test (pole test), the acacetin-treated mice showed decreased time of turning and locomotor activity, which were longer in MPTP-only treated mice. In addition, the acacetin-treated group inhibited degeneration of DA neurons and depletion of dopamine level induced by MPTP toxicity in the substantia nigra and striatum of the brain. Moreover, the acacetin-treated group inhibited microglia activation, accompanied by production of inducible nitric oxide synthases and cyclooxygenase-2. These results suggest that acacetin can protect DA neurons against the neurotoxicity involved in PD via its anti-inflammatory action.

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