Acacetin protects dopaminergic cells against 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine-induced neuroinflammation in vitro and in vivo

Kim, HG; Ju, MS; Ha, SK; Lee, H; Kim, SY; Oh, MS

Acacetin protects dopaminergic cells against 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine-induced neuroinflammation in vitro and in vivo

Kim, HG Ju, MS Ha, SK Lee, H

Kim, SY Oh, MS

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Publication Type:: Journal Article
Citation:: Biological and Pharmaceutical Bulletin, 2012, 35 (8), pp. 1287 - 1294
Issue Date:: 2012-08-01

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Field	Value	Language
dc.contributor.author	Kim, HG	en_US
dc.contributor.author	Ju, MS	en_US
dc.contributor.author	Ha, SK	en_US
dc.contributor.author	Lee, H https://orcid.org/0000-0002-1107-9389	en_US
dc.contributor.author	Kim, SY	en_US
dc.contributor.author	Oh, MS	en_US
dc.date.issued	2012-08-01	en_US
dc.identifier.citation	Biological and Pharmaceutical Bulletin, 2012, 35 (8), pp. 1287 - 1294	en_US
dc.identifier.issn	0918-6158	en_US
dc.identifier.uri	http://hdl.handle.net/10453/115410
dc.description.abstract	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. © 2012 The Pharmaceutical Society of Japan.	en_US
dc.relation.ispartof	Biological and Pharmaceutical Bulletin	en_US
dc.relation.isbasedon	10.1248/bpb.b12-00127	en_US
dc.subject.classification	Pharmacology & Pharmacy	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Inbred C57BL	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Parkinsonian Disorders	en_US
dc.subject.mesh	Parkinson Disease	en_US
dc.subject.mesh	Inflammation	en_US
dc.subject.mesh	1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine	en_US
dc.subject.mesh	Flavones	en_US
dc.subject.mesh	Neuroprotective Agents	en_US
dc.subject.mesh	Anti-Inflammatory Agents	en_US
dc.subject.mesh	Plant Extracts	en_US
dc.subject.mesh	Phytotherapy	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Dopaminergic Neurons	en_US
dc.title	Acacetin protects dopaminergic cells against 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine-induced neuroinflammation in vitro and in vivo	en_US
dc.type	Journal Article
utslib.citation.volume	8	en_US
utslib.citation.volume	35	en_US
utslib.for	0304 Medicinal and Biomolecular Chemistry	en_US
utslib.for	0607 Plant Biology	en_US
utslib.for	1115 Pharmacology and Pharmaceutical Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Health
utslib.copyright.status	closed_access
pubs.issue	8	en_US
pubs.publication-status	Published	en_US
pubs.volume	35	en_US

Abstract:

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. © 2012 The Pharmaceutical Society of Japan.

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