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Effects of Berberine on 6-hydroxydopamine-induced Parkinsonism in Rats  

Kwon, Ik-Hyun (College of Pharmacy, Chungbuk National University)
Choi, Hyun-Sook (College of Pharmacy, Chungbuk National University)
Shin, Kun-Seong (College of Pharmacy, Chungbuk National University)
Hwang, Bang-Yeon (College of Pharmacy, Chungbuk National University)
Lee, Myung-Koo (College of Pharmacy, Chungbuk National University)
Publication Information
Korean Journal of Pharmacognosy / v.40, no.4, 2009 , pp. 351-356 More about this Journal
Abstract
Many isoquinoline alkaloids including berberine lower dopamine content by reducing tyrosine hydroxylase (TH) activity 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 rat models were investigated. Berberine at 10-30 ${\mu}M$ did not affect cell viability in PC12 cells. However, berberine at concentrations higher than $50{\mu}M$ caused cytotoxicity at 24 h. Berberine (10-50 ${\mu}M$) also enhanced 6-OHDA (10-50 ${\mu}M$)-induced cytotoxicity at 24 h compared to 6-OHDA alone with an apoptotic process. In addition, treatment with berberine (5 and 30 mg/kg, i.p.) for three weeks showed a dopaminergic cell loss in substantia nigra of 6-OHDA-lesioned rats: 30 mg/kg berberine was more intensive cytotoxic. The levels of dopamine were also decreased by berberine (5 and 30 mg/kg) in the ipsilateral substantia nigra of 6-OHDA-lesioned rats. These results suggest that berberine aggravated 6-OHDA-induced cytotoxicity in PC12 cells and treatment with berberine (5 and 30 mg/kg) in 6-OHDA-lesioned rats also enhanced the degeneration of dopaminergic cell death and the decrease in dopamine levels in substantia nigra. Therefore, the long-term L-DOPA therapeutic patients with isoquinoline compounds including berberine may need to be checked for the adverse symptoms.
Keywords
Berberine; 6-Hydroxydopamine-induced cytotoxicity; Dopamine; PC12 cells; 6-Hydroxydopamine-lesioned rats;
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