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Planta Med. 2006 Feb;72(3):217-21.

A dual and opposite effect of Calendula officinalis flower extract: chemoprotector and promoter in a rat hepatocarcinogenesis model.

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Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del IPN (Cinvestav), San Pedro Zacatenco, CP, México.


Calendula officinalis extracts have protective and cytotoxic effects. We previously reported the dual activity of C. officinalis in primary rat hepatocyte cultures treated with N-nitrosodiethylamine. At nM concentrations it was anti-genotoxic while at microM concentrations it exhibited genotoxic effects. Here we tested the activity of Calendula officinalis in vivo in male Fischer 344 rats initiated with N-nitrosodiethylamine, promoted with 2-acetylaminofluorene, and 70 % partially hepatectomized. Liver gamma-glutamyltranspeptidase positively altered hepatocyte foci 25 days after initiation were our end point. The protective effect of C. officinalis started at 0.1 mg/kg concentration, increased at 0.5 mg/kg and reached its maximum at 2.5 mg/kg, when it decreased the area and number of altered foci by 55 % and 49 %, respectively, in comparison with rats treated only with carcinogen. At 5 mg/kg the number and area of altered hepatocyte foci were still lower, but almost reached the figures of carcinogen-treated rats. Ten and 20 mg/kg doses produced a notorious increment in the area and number of altered hepatic foci, and at 40 mg/kg of extract the increment was 40 % and 53 %, respectively. Additionally, when 2-acetylaminofluorene was substituted by a 40 mg/kg C. officinalis extract, a promoting effect was observed with increments of 175 % and 266 % in area and number of altered hepatocyte foci with respect to controls. When N-nitrosodiethylamine was substituted by 40 mg/kg of extract, the latter did not show initiator activity. In summary, we showed a protecting activity of C. officinalis at low doses, but doses above 10 mg/kg increased altered hepatocyte foci. This dual effect is an example of the phenomenon of hormesis. Furthermore, 40 mg/kg of dry weight extract administered instead of 2-acetylaminofluorene induced a clear promoting activity. These in vivo results are similar and consistent with those reported by us in primary rat liver cell cultures.

[Indexed for MEDLINE]

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