Plant pentacyclic triterpenic acids as modulators of lipid membrane physical properties

Abstract

Free triterpenic acids (TTPs) present in plants are bioactive compounds exhibiting multiple nutriceutical activities. The underlying molecular mechanisms have only been examined in part and mainly focused on anti-inflammatory properties, cancer and cardiovascular diseases, in all of which TTPs frequently affect membrane-related proteins. Based on the structural characteristics of TTPs, we assume that their effect on biophysical properties of cell membranes could play a role for their biological activity. In this context, our study is focused on the compounds, oleanolic (3β-hydroxy-12-oleanen-28-oic acid, OLA), maslinic (2α,3β-dihydroxy-12-oleanen-28-oic acid, MSL) and ursolic ((3β)-3-hydroxyurs-12-en-28-oic acid, URL) as the most important TTPs present in orujo olive oil. X-ray diffraction, differential scanning calorimetry, (31)P nuclear magnetic resonance and Laurdan fluorescence data provide experimental evidence that OLA, MSL and URL altered the structural properties of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) and DPPC-Cholesterol (Cho) rich membranes, being located into the polar-hydrophobic interphase. Specifically, in DPPC membranes, TTPs altered the structural order of the L(β'), phase without destabilizing the lipid bilayer. The existence of a nonbilayer isotropic phase in coexistence with the liquid crystalline L(α) phase, as observed in DPPC:URL samples, indicated the presence of lipid structures with high curvature (probably inverted micelles). In DPPC:Cho membranes, TTPs affected the membrane phase properties increasing the Laurdan GP values above 40°C. MSL and URL induced segregation of Cho within the bilayer, in contrast to OLA, that reduced the structural organization of the membrane. These results strengthen the relevance of TTP interactions with cell membranes as a molecular mechanism underlying their broad spectrum of biological effects.

Suppressive Effect of Maslinic Acid on PMA-induced Protein Kinase C in Human B-Lymphoblastoid Cells

“…Pentacyclic triterpenes are structurally similar to sterols and interaction with the cell membrane is thought to be the molecular mechanism underlying their biological effects. It has been suggested that maslinic acid binds to transmembrane domains and competes with cholesterol (Cho) for the hydrogen-bonded ester carbonyl groups, thereby disturbing the localization and the physiological function of membrane-related proteins (Prades et al, 2011).…”

Antioxidant effect of apple phenolic on lipid peroxidation in Chinese-style sausage

“…In addition, ursolic acid (RT), which was reported to be an effective antioxidant (Ramos et al 2010;Prades et al 2011;Ramachandran and Prasad 2008), showed a weaker antioxidative effect than BHT in our study. Buscailhon et al (1994) reported that the free fatty acids in cured meat product are mainly generated from the hydrolysis of phospholipids.…”

“…Antioxidant activity of phenolics extracted from apple (the main polyphenols are chlorogenic acid, phlorizin and phloretin) (Peschel et al 2006; Van der Sluis et al 2002;Sánchez-Rabaneda et al 2004) have been investigated. The aim of this study was to compare the effect of apple phenolics on lipid oxidation of Chinese-style sausage with ursolic acid, a triterpenoid antioxidant from rosemary (Ramos et al 2010;Prades et al 2011;Ramachandran and Prasad 2008), and butylated hydroxytoluene (BHT), a synthetic antioxidant widely used in the food industry.…”

Effect of Erythrodiol, A Natural Pentacyclic Triterpene from Olive Oil, on the Lipid Membrane Properties

“…The decrease of the transition enthalpy in the presence of a drug is usually attributed to the drug interaction with the hydrophobic chains of the bilayer (Detoni et al 2009;Koukoulitsa et al 2011;Potamitis et al 2011;Barenholz et al 2011). Compared to other pentacyclic triterpenes (Prades et al 2011) which did not affect significantly the melting temperature and the enthalpy of the main phase transition, erythrodiol produced remarkable decrease of the enthalpy values of the main peak (Table 2). Rodriguez et al (1997) demonstrated that cholesterol and a-amyrin, unlike other pentacyclic monoalcohols, are incorporated at high levels into DPPC bilayers and this was attributed to their planarity.…”

“…The structure of a triterpenic compound (Dufourc 2008;Prades et al 2011;Rodriguez et al 1997), the number of oxidized groups Pownall 2005, 2006), and the conjugation to a sugar structure (Lorent et al 2013;Hu et al 1996) are the factors that control the interaction and consequently the effects of triterpenic molecules on the membrane properties. Among the natural pentacyclic triterpenes, many reports have been published concerning the interaction with lipid membrane of lupeol (Rodriguez et al 1997;Broniatowski et al 2012a, b), betulinic acid (Broniatowski et al 2012a, b), betulin (Broniatowski et al 2012a), oleanolic, maslinic, ursolic acids (Prades et al 2011;Han et al 1997), alpha-amyrin, and taraxerol (Rodriguez et al 1997).…”