J Pharm Pharmacogn Res 3(suppl. 1): S61, 2015
Proceedings of the 4th International Symposium on Pharmacology of Natural Products FAPRONATURA 2015 September 21st-25th, 2015; Cuban Society of Pharmacology. Topes de Collantes, Sancti Spiritus, Cuba.
OC-43: THE CYTOTOXIC EFFECTS OF BROWN CUBAN PROPOLIS DEPEND ON THE NEMOROSONE CONTENT AND MAY BE MEDIATED BY MITOCHONDRIAL UNCOUPLING
Pardo-Andreu GL1, Núñez-Figueredo Y2, Delgado-Hernández R2, Cuesta-Rubio O3, Alberici LC4.
Introduction: Three main types of Cuban propolis directly related to their secondary metabolite composition have been identified: brown, red and yellow propolis; the former is majoritarian and is characterized by the presence of nemorosone. We recently reported that this molecule and its chemical analogues guttiferone A and clusianone presented strong cytotoxic effects mediated by mitochondrial uncoupling. Therefore, it can be hypothesize that the cytotoxic and antiparasitic effects of the brown Cuban propolis reported elsewhere may be related to their nemorosone’s content and mediated by a mitotoxic uncoupling effect. Material and Methods: Studies were performed in both hepatic carcinoma (HepG2) cells and primary rats hepatocytes. Mitochondria isolated from rat liver were also used. Results: In this study, brown Cuban propolis extracts were found cytotoxic against HepG2 cells and primary rat hepatocytes, in close association with the nemorosone contents. In mitochondria isolated from rat liver the extracts displayed uncoupling activity, which was demonstrated by the increase in succinate-supported state 4 respiration rates, dissipation of mitochondrial membrane potential, Ca2+ release from Ca2+-loaded mitochondria, and a marked ATP depletion. As in cells, the degree of such mitotoxic events was closely correlated to the nemorosone content. The propolis extracts that do not contain nemorosone were neither cytotoxic nor mitotoxic, except R-29, whose detrimental effect upon cells and mitochondria could be mediated by its isoflavonoids and chalcones components, well-known mitochondrial uncouplers. Conclusions: Our results at least partly unravel the cytotoxic mechanism of Cuban propolis, particularly regarding brown propolis, and raise concerns about the toxicological implication of Cuban propolis consumption.
Citation Format: Pardo-Andreu GL, Núñez-Figueredo Y, Delgado-Hernández R, Cuesta-Rubio O, Alberici LC (2015) The cytotoxic effects of brown Cuban propolis depend on the nemorosone content and may be mediated by mitochondrial uncoupling. [Abstract]. In: Proceedings of the FAPRONATURA 2015; 2015 Sep 21-25; Topes de Collantes, Sancti Spiritus: CSF. J Pharm Pharmacogn Res 3(Suppl. 1): S61. Abstract nr OC-43.