Potential antimutagenic activity of berberine, a constituent of Mahonia aquifolium.
BACKGROUND
As part of a study aimed at developing new pharmaceutical products from natural resources, the purpose of this research was twofold: (1) to fractionate crude extracts from the bark of Mahonia aquifolium and (2) to evaluate the strength of the antimutagenic activity of the separate components against one of the common direct-acting chemical mutagens.


METHODS
The antimutagenic potency was evaluated against acridine orange (AO) by using Euglena gracilis as an eukaryotic test model, based on the ability of the test compound/fraction to prevent the mutagen-induced damage of chloroplast DNA.


RESULTS
It was found that the antimutagenicity of the crude Mahonia extract resides in both bis-benzylisoquinoline (BBI) and protoberberine alkaloid fractions but only the protoberberine derivatives, jatrorrhizine and berberine, showed significant concentration-dependent inhibitory effect against the AO-induced chloroplast mutagenesis of E. gracilis. Especially berberine elicited, at a very low dose, remarkable suppression of the AO-induced mutagenicity, its antimutagenic potency being almost three orders of magnitude higher when compared to its close analogue, jatrorrhizine. Possible mechanisms of the antimutagenic action are discussed in terms of recent literature data. While the potent antimutagenic activity of the protoberberines most likely results from the inhibition of DNA topoisomerase I, the actual mechanism(s) for the BBI alkaloids is hard to be identified.


CONCLUSIONS
Taken together, the results indicate that berberine possesses promising antimutagenic/anticarcinogenic potential that is worth to be investigated further.
Cernáková
Marta
M
Department of Environmental Sciences, Faculty of Chemical Technology, Slovak Technical University, SK-81237 Bratislava, Slovak Republic. cernakm@chtf.stuba.sk
Kost'álová
Daniela
D
Kettmann
Viktor
V
Plodová
Miriam
M
Tóth
Jaroslav
J
Drímal
Ján
J
D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D001599:Berberine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005056:Euglena gracilis / Q000187:drug effects; D028143:Mahonia / Q000737:chemistry; D008517:Phytotherapy; D024301:Plant Bark; D010936:Plant Extracts / Q000494:pharmacology*
D016587:Antimutagenic Agents; D010936:Plant Extracts; C055785:jatrorrhizine; D001599:Berberine