Planta Med 2006; 72(3): 217-221
DOI: 10.1055/s-2005-916196
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

A Dual and Opposite Effect of Calendula officinalis Flower Extract: Chemoprotector and Promoter in a Rat Hepatocarcinogenesis Model

L. M. Barajas-Farias1 , J. I. Pérez-Carreón1 , E. Arce-Popoca1 , S. Fattel-Fazenda1 , L. Alemán-Lazarini1 , S. Hernández-García1 , M. Salcido-Neyoy1 , F. G. Cruz-Jiménez3 , J. Camacho2 , S. Villa-Treviño1
  • 1Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del IPN (Cinvestav), San Pedro Zacatenco, C.P., México
  • 2Sección Externa de Farmacología, Centro de Investigación y de Estudios Avanzados del IPN (Cinvestav), San Pedro Zacatenco, C.P., México
  • 3Departamento de Ciencias Biológicas, FES Cuautitlán, Universidad Nacional Autónoma de México (UNAM), México
Further Information

Publication History

Received: October 18, 2004

Accepted: August 8, 2005

Publication Date:
05 December 2005 (online)


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 μM 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 γ-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.




AHF:altered hepatocytes foci

RH:resistant hepatocyte model

AEE:Aqueous-ethanol extract



PH:partial hepatectomy


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