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Potential antimutagenic activity of berberine, a constituent of Mahonia aquifolium.

Cernáková M, Kost'álová D, Kettmann V, Plodová M, Tóth J, Drímal J - BMC Complement Altern Med (2002)

Bottom Line: 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.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.Taken together, the results indicate that berberine possesses promising antimutagenic/anticarcinogenic potential that is worth to be investigated further.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Environmental Sciences, Faculty of Chemical Technology, Slovak Technical University, SK-81237 Bratislava, Slovak Republic. cernakm@chtf.stuba.sk

ABSTRACT

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.

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Chemical structures of berberine and jatrorrhizine.
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Figure 1: Chemical structures of berberine and jatrorrhizine.

Mentions: Over the last decade, bis-benzylisoquinoline (BBI) and especially protoberberine alkaloids (e.g., berberine and jatrorrhizine; Fig. 1) have attracted considerable attention in this respect; protoberberines represent a structural class of organic cations and have been found to be predominantly distributed in several genera of the families Ranunculaceae and Berberidaceae (e.g., Berberis, Mahonia, Coptis). Berberine, a major representative of the protoberberine alkaloids, displays diverse biochemical and pharmacological actions while being relatively non-toxic to man; its antimicrobial activity has been demonstrated against many bacterial and fungal species [1-4]. The drug was subsequently screened for anti-cancer activity following evidence of antineoplastic properties [5-7]. It has also been shown that berberine exhibits the ability to induce apoptosis in promyelocytic leukemia HL-60 and 3T3 fibroblast cells [5,8]. In addition, some protoberberines are highly effective as cytotoxic agents against several carcinoma such as HeLa, SVKO(3), Hep-2, primary culture from mouse embryo and human fibroblast cells [9,10]; berberine showed consistently the highest cytotoxicity among the alkaloids tested. Only recently it has been reported that berberine possesses a dual topoisomerase I and II poisoning activity [11-13] and binds to double helical DNA with a high affinity [14]. Furthermore, computer modeling studies on protoberberine-DNA complexes suggest that these alkaloids are able to bind to the host DNA by both intercalative (through rings C and D; Fig. 1) and minor groove (rings A and B) binding modes [12,13].


Potential antimutagenic activity of berberine, a constituent of Mahonia aquifolium.

Cernáková M, Kost'álová D, Kettmann V, Plodová M, Tóth J, Drímal J - BMC Complement Altern Med (2002)

Chemical structures of berberine and jatrorrhizine.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC101396&req=5

Figure 1: Chemical structures of berberine and jatrorrhizine.
Mentions: Over the last decade, bis-benzylisoquinoline (BBI) and especially protoberberine alkaloids (e.g., berberine and jatrorrhizine; Fig. 1) have attracted considerable attention in this respect; protoberberines represent a structural class of organic cations and have been found to be predominantly distributed in several genera of the families Ranunculaceae and Berberidaceae (e.g., Berberis, Mahonia, Coptis). Berberine, a major representative of the protoberberine alkaloids, displays diverse biochemical and pharmacological actions while being relatively non-toxic to man; its antimicrobial activity has been demonstrated against many bacterial and fungal species [1-4]. The drug was subsequently screened for anti-cancer activity following evidence of antineoplastic properties [5-7]. It has also been shown that berberine exhibits the ability to induce apoptosis in promyelocytic leukemia HL-60 and 3T3 fibroblast cells [5,8]. In addition, some protoberberines are highly effective as cytotoxic agents against several carcinoma such as HeLa, SVKO(3), Hep-2, primary culture from mouse embryo and human fibroblast cells [9,10]; berberine showed consistently the highest cytotoxicity among the alkaloids tested. Only recently it has been reported that berberine possesses a dual topoisomerase I and II poisoning activity [11-13] and binds to double helical DNA with a high affinity [14]. Furthermore, computer modeling studies on protoberberine-DNA complexes suggest that these alkaloids are able to bind to the host DNA by both intercalative (through rings C and D; Fig. 1) and minor groove (rings A and B) binding modes [12,13].

Bottom Line: 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.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.Taken together, the results indicate that berberine possesses promising antimutagenic/anticarcinogenic potential that is worth to be investigated further.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Environmental Sciences, Faculty of Chemical Technology, Slovak Technical University, SK-81237 Bratislava, Slovak Republic. cernakm@chtf.stuba.sk

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus