Interaction of Artepillin C with model membranes
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Green propolis, a mixture of beeswax and resinous compounds processed by Apis mellifera, displays several pharmacological properties. Artepillin C, the major compound in green propolis, consists of two prenylated groups bound to a phenyl group. Several studies have focused on the therapeutic effects of Artepillin C, but there is no evidence that it interacts with amphiphilic aggregates to mimic cell membranes. We have experimentally and computationally examined the interaction between Artepillin C and model membranes composed of dimyristoylphosphatidylcholine (DMPC) because phosphatidylcholine (PC) is one of the most abundant phospholipids in eukaryotic cell membranes. PC is located in both outer and inner leaflets and has been used as a simplified membrane model and a non-specific target to study the action of amphiphilic molecules with therapeutic effects. Experimental results indicated that Artepillin C adsorbed onto the DMPC monolayers. Its presence in the lipid suspension pointed to an increased tendency toward unilamellar vesicles and to decreased bilayer thickness. Artepillin C caused point defects in the lipid structure, which eliminated the ripple phase and the pre-transition in thermotropic chain melting. According to molecular dynamics (MD) simulations, (1) Artepillin C aggregated in the aqueous phase before it entered the bilayer; (2) Artepillin C was oriented along the direction normal to the surface; (3) the negatively charged group on Artepillin C was accommodated in the polar region of the membrane; and (4) thinner regions emerged around the Artepillin C molecules. These results help an understanding of the molecular mechanisms underlying the biological action of propolis.
KeywordsDMPC Model membranes Artepillin C Green propolis Langmuir monolayer
We thank Dr. Georg Pabst for help with the GAP software, Dr. Galina Borissevitch for useful discussion on the monolayer experiments and Cynthia Maria de Campos Prado Manso for helping to revise the English language. The research was supported by the Brazilian agencies CAPES, CNPq (Process Numbers 232302/2014-6 and 304981/2012-5), and FAPESP (Process Number 2014/26895). This research is part of the research program of the Dutch Polymer Institute (DPI), projects #772a and #772ap.
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