期刊
BIOLOGICAL & PHARMACEUTICAL BULLETIN
卷 35, 期 8, 页码 1287-1294出版社
PHARMACEUTICAL SOC JAPAN
DOI: 10.1248/bpb.b12-00127
关键词
acacetin; Parkinson's disease; neuroprotection; 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; anti-inflammation
资金
- National Research Foundation of Korea (NRF)
- Ministry of Education, Science and Technology [2005-0049404]
- National Research Council of Science & Technology (NST), Republic of Korea [E0131700] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [과06A2601, 과06A2101, 2005-0049739] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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 E-2, and tumor necrosis factor-alpha against MPP+-induced toxicity in a dose-dependent manner. Then, we confirmed the effect of acacetin (10mg/kg/d for 3d, per os (p.o.)) in a mouse model of PD induced by MPTP (30mg/kg/d for 5d, 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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