title: Effects of berberine on 6-hydroxydopamine-induced neurotoxicity in PC12 cells and a rat model of Parkinson's disease.
abstract: Protoberberine isoquinoline alkaloids including berberine inhibit dopamine biosynthesis and aggravate l-DOPA-induced cytotoxicity in PC12 cells. In this study, the effects of berberine on 6-hydroxydopamine (6-OHDA)-induced cytotoxicity in PC12 cells and on unilateral 6-OHDA-lesioned rats were investigated. In PC12 cells, berberine at 10 and 30μM associated with 6-OHDA (10, 20, and 50μM) enhanced cytotoxicity at 48h compared to 6-OHDA alone, indicated by an increase in apoptotic cell death. In addition, treatment with berberine (5 and 30mg/kg, i.p.) for 21 days in 6-OHDA-lesioned rats markedly depleted tyrosine hydroxylase-immunopositive cells in the substantia nigra as compared to berberine-untreated rats. Further, the levels of dopamine and norepinephrine were also significantly decreased by berberine administration (5 and 30mg/kg) in the striatal regions of 6-OHDA-lesioned rats. These results suggested that berberine aggravated 6-OHDA-induced cytotoxicity in PC12 cells, and led to the degeneration of dopaminergic neuronal cells in the substantia nigra of 6-OHDA-lesioned rats. It is, therefore, suggested that the use of long-term l-DOPA therapy with isoquinoline derivatives including berberine may need to be examined for the presence of adverse symptoms.
authors.affiliation: College of Pharmacy, Chungbuk National University, Heungduk-gu, Cheongju 361-763, Republic of Korea.
authors.forename: Ik Hyun
authors.initials: IH
authors.lastname: Kwon
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Choi
authors.forename: Kun Seong
authors.initials: KS
authors.lastname: Shin
authors.forename: Byung Koo
authors.initials: BK
authors.lastname: Lee
authors.forename: Chong Kil
authors.initials: CK
authors.lastname: Lee
authors.forename: Bang Yeon
authors.initials: BY
authors.lastname: Hwang
authors.forename: Sung Cil
authors.initials: SC
authors.lastname: Lim
authors.forename: Myung Koo
authors.initials: MK
authors.lastname: Lee
mesh_terms: D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D020258:Neurotoxicity Syndromes / Q000378:metabolism / Q000473:pathology*; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity*; D016716:PC12 Cells; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D001599:Berberine; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D009638:Norepinephrine