Dietary manipulations during the early postnatal period are associated with the development of metabolic disorders including non-alcoholic fatty liver disease (NAFLD) or long-term protection against metabolic dysfunction. We investigated the potential hepatoprotective effects of neonatal administration of oleanolic acid (OA), a phytochemical, on the subsequent development in adulthood, of dietary fructose-induced NAFLD. Male and female suckling rats (n=112) were gavaged with; distilled water (DW), OA (60 mg/kg), high fructose solution (HF; 20% w/v) and OA+HF (OAHF) for 7 days. The rats were weaned onto normal rat chow on day 21 up to day 55. From day 56, half of the rats in each treatment group were continued on plain water or HF as drinking fluid for 8 weeks. Hepatic lipid accumulation and hepatic histomorphometry were then determined. Fructose consumption in adulthood following neonatal fructose intake (HF+F) caused a 47–49% increase in hepatic lipid content of both male and female rats (P<0.05). However, fructose administered in adulthood only, caused a significant increase (P<0.05) in liver lipid content in females only. NAFLD activity scores for inflammation and steatosis were higher in the fructose-fed rats compared with other groups (P<0.05). Steatosis, low-grade inflammation and fibrosis were observed in rats that received HF+F. NAFLD area fraction for fibrosis was three times higher in rats that received fructose neonatally and in adulthood compared with the rats in the negative control group (P<0.05). Treatment with OA during a critical window of developmental plasticity in rats prevented the development of fructose-induced NAFLD.

Pomace olive oil (POM), an olive oil subproduct traditionally used in Spain, is a good source of minor components from the unsaponifiable fraction such as triterpenoids, mainly in the form of oleanolic acid, which induces vascular protection and vasodilatation. Our aim was to evaluate the effects of long-term intake of diets enriched in POM with high concentration in oleanolic acid on endothelial dysfunction associated to hypertension in small mesenteric arteries (SMA) from spontaneously hypertensive rats (SHR). During 12 weeks, rats (six rats per group) were fed either a control 2 % maize oil diet (BD), or high-fat diets containing 15 % refined olive oil (OL), pomace olive oil (POM), or pomace olive oil supplemented in oleanolic acid (POMO; up to 800 parts per million). Endothelial and vascular functions were assessed by relaxing or contracting responses to acetylcholine (ACh) or phenylephrine, respectively. The involvement of endothelium-derived relaxing factors in these responses was evaluated. In contrast to BD, SHR fed high-fat diets showed a biphasic response to ACh related to changes in eicosanoid metabolism. POM enhanced the endothelial function in SMA from SHR by increasing the endothelium-derived hyperpolarising factor (EDHF)-type component, whereas administration of POMO resulted in a similar contribution of NO/EDHF in the endothelial response to ACh. The present study shows that despite the lack of changes in blood pressure, consumption of POM improves endothelial function in SMA from SHR by improving the agonist-mediated EDHF/NO response. Thus, triterpenoids confer a protective role to POM against endothelial dysfunction in hypertension.

We have previously reported the anticarcinogenic effects of an olive fruit extract composed of pentacyclic triterpenes, the main components of which are maslinic acid (73·25 %) and oleanolic acid (25·75 %). Here we examined the effects of the individual components on proliferation, necrosis and apoptosis rates by fluorescence-based techniques in human HT-29 colon cancer cells. Oleanolic acid showed moderate antiproliferative activity, with an ec50 of 160·6 (se 10·6) μmol/l, and moderate cytotoxicity at high concentrations ( ≥ 250 μmol/l). On the other hand, maslinic acid inhibited cell growth with an ec50 of 101·2 (se 7·8) μmol/l, without necrotic effects. Oleanolic acid, which lacks a hydroxyl group at the carbon 2 position, failed to activate caspase-3 as a prime apoptosis protease. In contrast, maslinic acid increased caspase-3-like activity at 10, 25 and 50 μmol/l by 3-, 3·5- and 5-fold over control cells, respectively. The detection of ROS in the mitochondria, which serve as pro-apoptotic signal, evidenced the different bioactivity of the two triterpenes. Confocal microscopy analysis revealed that maslinic acid generated superoxide anions while oleanolic acid-treated cells did not differ from the control. Completion of apoptosis by maslinic acid was confirmed microscopically by the increase in plasma membrane permeability, and detection of DNA fragmentation. In conclusion, the anticancer activity observed for olive fruit extracts seems to originate from maslinic acid but not from oleanolic acid. Maslinic acid therefore is a promising new compound for the chemoprevention of colon cancers.

‘Orujo’ olive oil is obtained by chemical processes from the waste resulting from the mechanical extraction of virgin olive oil. The aim of the present study was to evaluate a new pharmacological property of two natural triterpenoids contained in olive oil, as vasodilatory agents, and to determine their mechanism of action. The two compounds studied were oleanolic acid and erythrodiol. The vasorelaxant effect induced by these pentacyclic triterpenoids was studied in isolated thoracic rat aorta. Oleanolic acid and erythrodiol, accumulatively added, showed vasorelaxant activities in aortic rings with endothelium pre-contracted by 10−6 M-phenylephrine (maximum percentage of relaxation 86·38 (SEM 2·89) and 73·53 (SEM 6·01), respectively). They had almost no relaxant effect on depolarised or endothelium-denuded aortic segments. The relaxation was significantly attenuated by pre-treatment with the NO synthase inhibitor Nω-nitro-L-arginine-methylester (L-NAME; 3×10−4 m). To characterise the involvement of endothelial factors, in addition to NO, arteries with endothelium were exposed to 10−5 M-indomethacin (INDO), a cyclo-oxygenase inhibitor, or INDO plus L-NAME. INDO did not have any significant effect on the relaxant response of both compounds. The combination of L-NAME plus INDO only abolished the oleanolic acid-induced relaxation. The present results suggest that the mechanism of relaxation seems to be mainly mediated by the endothelial production of NO; however, other mechanisms cannot be excluded. It can be concluded that oleanolic acid and erythrodiol may have interesting therapeutic potential as new vasodilator drugs, thus protecting the cardiovascular system. Therefore, the intake of ‘orujo’ olive oil, as a source of these compounds, might be beneficial in this regard.