Effects of berberine on 6-hydroxydopamine-induced neurotoxicity in PC12 cells and a rat model of Parkinson's disease.
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.
Kwon
Ik Hyun
IH
College of Pharmacy, Chungbuk National University, Heungduk-gu, Cheongju 361-763, Republic of Korea.
Choi
Hyun Sook
HS
Shin
Kun Seong
KS
Lee
Byung Koo
BK
Lee
Chong Kil
CK
Hwang
Bang Yeon
BY
Lim
Sung Cil
SC
Lee
Myung Koo
MK
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
D001599:Berberine; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D009638:Norepinephrine