Effects of berberine on 6-hydroxydopamine-induced neurotoxicity in PC12 cells and a rat model of Parkinson's disease

• Published in: Neuroscience letters 2010-12, Vol.486 (1), p.29-33
• Main Authors: Kwon, Ik Hyun, Choi, Hyun Sook, Shin, Kun Seong, Lee, Byung Koo, Lee, Chong Kil, Hwang, Bang Yeon, Lim, Sung Cil, Lee, Myung Koo
• Format: Article
• Language: English
• Subjects: 6-Hydroxydopamine-induced cytotoxicity; 6-Hydroxydopamine-lesioned rats; Animals; Berberine; Berberine - pharmacology; Biological and medical sciences; Cell Death - drug effects; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Models, Animal; Dopamine - metabolism; Dopaminergic neuronal cells; Dose-Response Relationship, Drug; Drug Synergism; Fundamental and applied biological sciences. Psychology; Male; Medical sciences; Neurology; Neurotoxicity Syndromes - metabolism; Neurotoxicity Syndromes - pathology; Norepinephrine - metabolism; Oxidopamine - toxicity; Parkinsonian Disorders - chemically induced; Parkinsonian Disorders - metabolism; Parkinsonian Disorders - pathology; PC12 Cells; Rats; Rats, Sprague-Dawley; Substantia Nigra - drug effects; Substantia Nigra - metabolism; Tyrosine 3-Monooxygenase - metabolism; Vertebrates: nervous system and sense organs
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2010.09.038

[Display omitted] ▶ Berberine is one of protoberberine isoquinoline alkaloids. ▶ Aggravation of 6-hydroxydopamine (6-OHDA)-induced cytotoxicity in PC12 cells. ▶ Enhancement of the degeneration of dopaminergic neuronal cells in the substantia nigra of 6-OHDA-lesioned rats. ▶ It is 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. 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 30 μM associated with 6-OHDA (10, 20, and 50 μM) enhanced cytotoxicity at 48 h compared to 6-OHDA alone, indicated by an increase in apoptotic cell death. In addition, treatment with berberine (5 and 30 mg/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 30 mg/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.