title: Silibinin suppresses astroglial activation in a mouse model of acute Parkinson's disease by modulating the ERK and JNK signaling pathways.
abstract: Parkinson's disease (PD) is the second-most common neurodegenerative disease after Alzheimer's disease, and is characterized by dopaminergic neuronal loss in midbrain. The MPTP-induced PD model has been well characterized by motor deficits and selective dopaminergic neuronal death accompanied by glial activation. Silibinin is a constituent of silymarin, an extract of milk thistle seeds, and has been proposed to have hepatoprotective, anti-cancer, anti-oxidative, and neuroprotective effects. In the present study, the authors studied the neuroprotective effects of silibinin in an acute MPTP model of PD. Silibinin was administered for 2 weeks, and then MPTP was administered to mice over 1 day (acute MPTP induced PD). Silibinin pretreatment effectively ameliorated motor dysfunction, dopaminergic neuronal loss, and glial activations caused by MPTP. In addition, an in vitro study demonstrated that silibinin suppressed astroglial activation and ERK and JNK phosphorylation in primary astrocytes in response to MPP(+) treatment. These findings show silibinin protected dopaminergic neurons in an acute MPTP-induced mouse model of PD, and suggest its neuroprotective effects might be mediated by the suppression of astrocyte activation via the inhibition of ERK and JNK phosphorylation. In conclusion, the study indicates silibinin should be viewed as a potential treatment for PD and other neurodegenerative diseases associated with neuroinflammation.
authors.affiliation: Department of Pharmacy, College of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Yujeong
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Pharmacy, College of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Hye Jeong
authors.initials: HJ
authors.lastname: Chun
authors.affiliation: Department of Pharmacy, College of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Kyung Moon
authors.initials: KM
authors.lastname: Lee
authors.affiliation: Department of Pharmacy, College of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Young-Suk
authors.initials: YS
authors.lastname: Jung
authors.affiliation: Department of Pharmacy, College of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 609-735, Republic of Korea. Electronic address: neuron@pusan.ac.kr.
authors.forename: Jaewon
authors.initials: J
authors.lastname: Lee
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000737:chemistry / Q000627:therapeutic use*; D001253:Astrocytes / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020267:MPTP Poisoning / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D000077385:Silybin; D012838:Silymarin / Q000737:chemistry / Q000627:therapeutic use*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D005904:Glial Fibrillary Acidic Protein; D012838:Silymarin; D000077385:Silybin; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase
keywords: Anti-inflammatory; Astrocyte; MAPK; MPTP; Parkinson׳s disease; Silibinin