title: Auraptene and Other Prenyloxyphenylpropanoids Suppress Microglial Activation and Dopaminergic Neuronal Cell Death in a Lipopolysaccharide-Induced Model of Parkinson's Disease.
abstract: In patients with Parkinson's disease (PD), hyperactivated inflammation in the brain, particularly microglial hyperactivation in the substantia nigra (SN), is reported to be one of the triggers for the delayed loss of dopaminergic neurons and sequential motor functional impairments. We previously reported that (1) auraptene (AUR), a natural prenyloxycoumain, suppressed inflammatory responses including the hyperactivation of microglia in the ischemic brain and inflamed brain, thereby inhibiting neuronal cell death; (2) 7-isopentenyloxycoumarin (7-IP), another natural prenyloxycoumain, exerted anti-inflammatory and neuroprotective effects against excitotoxicity; and (3) 4'-geranyloxyferulic acid (GOFA), a natural prenyloxycinnamic acid, also exerted anti-inflammatory effects. In the present study, using an intranigral lipopolysaccharide (LPS)-induced PD-like mouse model, we investigated whether AUR, 7-IP, and GOFA suppress microglial activation and protect against dopaminergic neuronal cell death in the SN. We successfully showed that these prenyloxyphenylpropanoids exhibited these prospective abilities, suggesting the potential of these compounds as neuroprotective agents for patients with PD.
authors.affiliation: Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan. sokuyama@cc.matsuyama-u.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okuyama
authors.affiliation: Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan. mu.yakuri.001@gmail.com.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Semba
authors.affiliation: Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan. kowagari77@yahoo.co.jp.
authors.forename: Nobuki
authors.initials: N
authors.lastname: Toyoda
authors.affiliation: Department of Pharmacy, University "G. D'Annunzio", Chieti-Pescara Via dei Vestini 31, Chieti Scalo 66100, Italy. fepifano@unich.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Epifano
authors.affiliation: Department of Pharmacy, University "G. D'Annunzio", Chieti-Pescara Via dei Vestini 31, Chieti Scalo 66100, Italy. s.genovese@unich.it.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Genovese
authors.affiliation: Department of Pharmacy, University "G. D'Annunzio", Chieti-Pescara Via dei Vestini 31, Chieti Scalo 66100, Italy. serena.fiorito@unich.it.
authors.forename: Serena
authors.initials: S
authors.lastname: Fiorito
authors.affiliation: Department of Pharmacy, University "G. D'Annunzio", Chieti-Pescara Via dei Vestini 31, Chieti Scalo 66100, Italy. vito.taddeo@unich.it.
authors.forename: Vito Alessandro
authors.initials: VA
authors.lastname: Taddeo
authors.affiliation: Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan. 46140018@cc.matsuyama-u.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sawamoto
authors.affiliation: Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan. mnakajim@cc.matsuyama-u.ac.jp.
authors.forename: Mitsunari
authors.initials: M
authors.lastname: Nakajima
authors.affiliation: Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan. furukawa@cc.matsuyama-u.ac.jp.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Furukawa
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000378:metabolism; D016923:Cell Death; D003373:Coumaric Acids / Q000494:pharmacology*; D003374:Coumarins / Q000494:pharmacology*; D059290:Dopaminergic Neurons / Q000166:cytology / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010300:Parkinson Disease / Q000188:drug therapy*; D013378:Substantia Nigra / Q000166:cytology / Q000378:metabolism*
chemical_list: C552732:4'-geranyloxyferulic acid; C461443:7-isopentenyloxycoumarin; D000893:Anti-Inflammatory Agents; D003373:Coumaric Acids; D003374:Coumarins; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; C105832:aurapten
keywords: 4′-geranyloxyferulic acid; 7-isopentenyloxycoumarin; Parkinson’s disease; anti-inflammation; auraptene; microglia; neuroprotection; prenyloxyphenylpropanoids; substantia nigra