Polyphenols and Triterpenes Combination in an In Vitro Model of Cardiac Damage: Protective Effects.

Olive products contain high levels of monounsaturated fatty acids as well as other minor components such as triterpenic alcohols and other pentacyclic triterpenes, which together form the main triterpenes of virgin olive oil. Olive fruits and leaves contain significant amounts of hydrophilic and lipophilic bioactives including flavones, phenolic acids and phenolic alcohols, amongst others. Several studies have shown the benefits of these substances on the cardiovascular system. Regardless, little is known about the specific combination of bioactive compounds in cardiovascular health. Thus, we aimed to test the combination of a triterpenes (TT70) and a polyphenols (HT60) olive oil bioactive extract in H9c2 cells under stress conditions: LPS and H2O2 stimulation. To evaluate the effectiveness of the combination, we measured cell viability, superoxide production and protein expression of caspase 3, eNOS, peNOS, TNF-α and Il-6. Overall, cells stimulated with LPS or H2O2 and co-incubated with the combination of triterpenes and polyphenols had increased cell survival, lower levels of superoxide anion, lower protein expression of eNOS and higher expression of peNOS, increased protein expression of SOD-1 and lower protein expression of TNF-α and Il-6. The specific combination of HT60+TT70 is of great interest for further study as a possible treatment for cardiovascular damage.

Olive juice dry extract containing hydroxytyrosol, as a nontoxic and safe substance: Results from pre-clinical studies and review of toxicological studies.

Products derived from olives, such as the raw fruit and oils, are widely consumed due to their taste, and purported nutritional/health benefits. Phenolic compounds, especially hydroxytyrosol (HT), have been proposed as one of the key substances involved in these effects. An olive juice extract, standardized to contain 20% HT ("OE20HT"), was produced to investigate its health benefits. The aim of this study was to demonstrate the genotoxic safety of this ingredient based on in vitro Ames assay and in vitro micronucleus assay. Results indicated that OE20HT was not mutagenic at concentrations of up to 5000 µg/plate, with or without metabolic activation, and was neither aneugenic nor clastogenic after 3-hour exposure at concentrations of up to 60 µg/mL with or without metabolic activation, or after 24-hour exposure at concentrations of up to 40 µg/mL. To further substantiate the safety of OE20HT following ingestion without conducting additional animal studies, a comprehensive literature review was conducted. No safety concerns were identified based on acute or sub-chronic studies in animals, including reproductive and developmental studies. These results were supported by clinical studies demonstrating the absence of adverse effects after oral supplementation with olive extracts or HT. Based on in vitro data and the literature review, the OE20HT extract is therefore considered as safe for human consumption at doses up to 2.5 mg/kg body weight/day.

Microemulsions Enhance the In Vitro Antioxidant Activity of Oleanolic Acid in RAW 264.7 Cells.

Oleanolic acid (OA) is the main triterpenic acid of olive leaves known for numerous pharmacological properties, including antioxidant activity. However, it is poorly soluble in water and consequently with low bioavailability, which limits its pharmacological application. Microemulsions (MEs) are dispersed systems consisting of two immiscible phases that promote rapid solubilization and absorption in the gastrointestinal tract. To improve both solubility and intestinal permeability of this molecule, OA has been formulated in two different microemulsions (ME-1 and ME-2). A solubility screening was carried out to select the ME components, and pseudoternary phase diagrams were constructed to evaluate the region of existence and select the appropriate amount of the constituents. ME-1 was prepared using Capmul PG-8/NF as the oily phase, and Transcutol and Tween 20 (7:3) as surfactants, while ME-2 contained Nigella oil and Isopropil myristate as the oily phase, and Transcutol HP and Cremophor EL (2:1) as surfactants. The OA solubility was increased by 1000-fold and 3000-fold in ME-1-OA and ME-2-OA, respectively. The MEs' droplet size and the PdI were evaluated, and the stability was assessed for 8 weeks by monitoring chemical and physical parameters. The parallel artificial membrane permeability assay (PAMPA) also demonstrated an enhanced intestinal permeability of both OA formulations compared with free OA. The potential ability of both MEs to enhance the bioactivity of OA against LPS-induced oxidative stress in RAW 264.7 murine macrophages was also investigated. Overall, this study suggests that both MEs promote a bio-enhancement of the protective action of OA against the LPS-induced pro-oxidant stress in macrophages. Overall, this study suggests that MEs could be an interesting formulation to improve OA oral bioavailability with potential clinical applications.

Pomegranate Extract Augments Energy Expenditure Counteracting the Metabolic Stress Associated with High-Fat-Diet-Induced Obesity.

Obesity is associated to a low grade of chronic inflammation leading to metabolic stress, insulin resistance, metabolic syndrome, dislipidemia, cardiovascular disease, and even cancer. A Mediterranean diet has been shown to reduce systemic inflammatory factors, insulin resistance, and metabolic syndrome. In this scenario, precision nutrition may provide complementary approaches to target the metabolic alterations associated to "unhealthy obesity". In a previous work, we described a pomegranate extract (PomE) rich in punicalagines to augment markers of browning and thermogenesis in human differentiated adipocytes and to augment the oxidative respiratory capacity in human differentiated myocytes. Herein, we have conducted a preclinical study of high-fat-diet (HFD)-induced obesity where PomE augments the systemic energy expenditure (EE) contributing to a reduction in the low grade of chronic inflammation and insulin resistance associated to obesity. At the molecular level, PomE promotes browning and thermogenesis in adipose tissue, reducing inflammatory markers and augmenting the reductive potential to control the oxidative stress associated to the HFD. PomE merits further investigation as a complementary approach to alleviate obesity, reducing the low grade of chronic inflammation and metabolic stress.

The Effectiveness of Rhodiola rosea L. Preparations in Alleviating Various Aspects of Life-Stress Symptoms and Stress-Induced Conditions-Encouraging Clinical Evidence.

Rhodiola rosea L. has a long history of use in traditional medicine to stimulate the nervous system, treat stress-induced fatigue and depression, enhance physical performance and work productivity and treat gastrointestinal ailments and impotence. Apart from its well-established traditional use, a significant number of publications on the clinical efficacy of various R. rosea preparations can be found in the literature. The majority of these studies are related to the efficacy of R. rosea in terms of cognitive functions and mental performance, including various symptoms of life-stress, fatigue and burnout. The beneficial effects of this medicinal plant on enhancing physical performance have also been evaluated in professional athletes and non-trained individuals. Moreover, even though most evidence originates from pre-clinical trials, several clinical studies have additionally demonstrated the remediating effects of R. rosea on cardiovascular and reproductive health by addressing non-specific stress damage and reversing or healing the disrupted physiologies and disfunctions. Overall, in accordance with its aim, the results presented in this review provide an encouraging basis for the clinical efficacy of R. rosea preparations in managing various aspects of stress-induced conditions.

Triterpenes from Olea europaea modulate in vitro ruminal fermentation.

Bioactive compounds present in Olea europaea have shown promising antimicrobial potential as an alternative to conventional coccidiostats. These effects are exerted by triterpenic acids (TT) present in the olive plant, namely, oleanolic acid (OA), ursolic acid (UA), and maslinic acid (MA). The objective of this study was to determine the effects of OA, UA, and MA on in vitro ruminal fermentation in comparison with monensin (MON). The study consisted of two experiments conducted as randomized complete block designs using bahiagrass hay or a high-concentrate mixed ration as basal substrates. In the first experiment (Exp. 1), a batch culture was performed with increasing doses of OA, UA, or MA. In Exp. 2, to increase the solubility of OA, two chemical forms were evaluated: a sodium salt (OA-NA) or a phyto-phospholipid complex (OA-PHYT) at 0, 4, 40, 100, and 200 mg/L of incubation inoculum. In both experiments, the dose 0 was used as control (CTL) and monensin (MON) as a positive control. Data were analyzed as a randomized complete block design with a factorial arrangement of treatments. For Exp. 2, orthogonal polynomial contrasts, adjusted for unequal spacing were used to determine the linear effects of increasing doses of OA-NA and OA-PHYT. In Exp. 1, OA reduced the concentration of CH4 in the high-concentrate substrate compared with CTL (P = 0.04). In Exp. 2 the total gas production was linearly decreased with increasing doses of OA-NA in both substrates (P ≤ 0.02). Furthermore, OA-NA and OA-PHYT decreased in vitro organic matter digestibility (P < 0.01) in the bahiagrass substrate to the same extent that MON did. However, the concentration of CH4/g of incubated DM was only reduced by the highest doses of OA-NA (P < 0.02). Lastly, no effects were observed for total VFA nor the VFA profile; however, OA-NA linearly decreased the A:P ratio in the bahiagrass substrate (P = 0.03). In conclusion, the acid form of OA as well as the sodium salt and phyto-phospholipid complex of OA were able to modify some fermentation parameters in this study; however, the magnitude of the responses was lower compared with monensin. Future studies should test OA in vivo to determine if the effects on ruminal fermentation observed here can translate into improve production efficiency while reducing carbon emissions.

Solubility and Permeability Enhancement of Oleanolic Acid by Solid Dispersion in Poloxamers and γ-CD.

Oleanolic acid (OA) is a pentacyclic triterpenoid widely found in the Oleaceae family, and it represents 3.5% of the dry weight of olive leaves. OA has many pharmacological activities, such as hepatoprotection, anti-inflammatory, anti-oxidant, anti-diabetic, anti-tumor, and anti-microbic activities. Its therapeutic application is limited by its poor water solubility, bioavailability, and permeability. In this study, solid dispersions (SDs) were developed to overcome these OA limitations. Solubility studies were conducted to evaluate different hydrophilic polymers, drug-to-polymer ratios, and preparation methods. Poloxamer 188, Poloxamer 407, and γ-CD exhibited the highest increases in terms of OA solubility, regardless of the method of preparation. Binary systems were characterized using differential scanning calorimetry (DSC), X-ray diffraction (XRPD), and Fourier transform infrared spectroscopy (FTIR). In addition, pure compounds and SDs were analyzed using scanning electron microscopy (SEM) in order to observe both the morphology and the particle surface. In vitro dissolution studies were performed for P407, P188, and γ-CD SDs. Preparation using the solvent evaporation method (SEM) produced the highest increase in the dissolution profiles of all three polymers with respect to the OA solution. Finally, the effect of SDs on OA permeability was evaluated with an in vitro parallel artificial membrane permeability assay (PAMPA). The formulation improved passive permeation across the simulated barrier due to OA increased solubility. The dissolution and PAMPA results indicate that the amorphization of OA by SD preparation could be a useful method to enhance its oral absorption, and it is also applicable on an industrial scale.

The GB4.0 Platform, an All-In-One Tool for CRISPR/Cas-Based Multiplex Genome Engineering in Plants.

CRISPR/Cas ability to target several loci simultaneously (multiplexing) is a game-changer in plant breeding. Multiplexing not only accelerates trait pyramiding but also can unveil traits hidden by functional redundancy. Furthermore, multiplexing enhances dCas-based programmable gene expression and enables cascade-like gene regulation. However, the design and assembly of multiplex constructs comprising tandemly arrayed guide RNAs (gRNAs) requires scarless cloning and is still troublesome due to the presence of repetitive sequences, thus hampering a more widespread use. Here we present a comprehensive extension of the software-assisted cloning platform GoldenBraid (GB), in which, on top of its multigene cloning software, we integrate new tools for the Type IIS-based easy and rapid assembly of up to six tandemly-arrayed gRNAs with both Cas9 and Cas12a, using the gRNA-tRNA-spaced and the crRNA unspaced approaches, respectively. As stress tests for the new tools, we assembled and used for Agrobacterium-mediated stable transformation a 17 Cas9-gRNAs construct targeting a subset of the Squamosa-Promoter Binding Protein-Like (SPL) gene family in Nicotiana tabacum. The 14 selected genes are targets of miR156, thus potentially playing an important role in juvenile-to-adult and vegetative-to-reproductive phase transitions. With the 17 gRNAs construct we generated a collection of Cas9-free SPL edited T1 plants harboring up to 9 biallelic mutations and showing leaf juvenility and more branching. The functionality of GB-assembled dCas9 and dCas12a-based CRISPR/Cas activators and repressors using single and multiplexing gRNAs was validated using a Luciferase reporter with the Solanum lycopersicum Mtb promoter or the Agrobacterium tumefaciens nopaline synthase promoter in transient expression in Nicotiana benthamiana. With the incorporation of the new web-based tools and the accompanying collection of DNA parts, the GB4.0 genome edition turns an all-in-one open platform for plant genome engineering.

Natural Extracts to Augment Energy Expenditure as a Complementary Approach to Tackle Obesity and Associated Metabolic Alterations.

Obesity is the epidemic of the 21st century. In developing countries, the prevalence of obesity continues to rise, and obesity is occurring at younger ages. Obesity and associated metabolic stress disrupt the whole-body physiology. Adipocytes are critical components of the systemic metabolic control, functioning as an endocrine organ. The enlarged adipocytes during obesity recruit macrophages promoting chronic inflammation and insulin resistance. Together with the genetic susceptibility (single nucleotide polymorphisms, SNP) and metabolic alterations at the molecular level, it has been highlighted that key modifiable risk factors, such as those related to lifestyle, contribute to the development of obesity. In this scenario, urgent therapeutic options are needed, including not only pharmacotherapy but also nutrients, bioactive compounds, and natural extracts to reverse the metabolic alterations associated with obesity. Herein, we first summarize the main targetable processes to tackle obesity, including activation of thermogenesis in brown adipose tissue (BAT) and in white adipose tissue (WAT-browning), and the promotion of energy expenditure and/or fatty acid oxidation (FAO) in muscles. Then, we perform a screening of 20 natural extracts (EFSA approved) to determine their potential in the activation of FAO and/or thermogenesis, as well as the increase in respiratory capacity. By means of innovative technologies, such as the study of their effects on cell bioenergetics (Seahorse bioanalyzer), we end up with the selection of four extracts with potential application to ameliorate the deleterious effects of obesity and the chronic associated inflammation.

Precision Nutrition to Activate Thermogenesis as a Complementary Approach to Target Obesity and Associated-Metabolic-Disorders.

Obesity is associated to increased incidence and poorer prognosis in multiple cancers, contributing to up to 20% of cancer related deaths. These associations are mainly driven by metabolic and inflammatory changes in the adipose tissue during obesity, which disrupt the physiologic metabolic homeostasis. The association between obesity and hypercholesterolemia, hypertension, cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) is well known. Importantly, the retrospective analysis of more than 1000 epidemiological studies have also shown the positive correlation between the excess of fatness with the risk of cancer. In addition, more important than weight, it is the dysfunctional adipose tissue the main driver of insulin resistance, metabolic syndrome and all cause of mortality and cancer deaths, which also explains why normal weight individuals may behave as "metabolically unhealthy obese" individuals. Adipocytes also have direct effects on tumor cells through paracrine signaling. Downregulation of adiponectin and upregulation of leptin in serum correlate with markers of chronic inflammation, and crown like structures (CLS) associated to the adipose tissue disfunction. Nevertheless, obesity is a preventable risk factor in cancer. Lifestyle interventions might contribute to reduce the adverse effects of obesity. Thus, Mediterranean diet interventional studies have been shown to reduce to circulation inflammatory factors, insulin sensitivity and cardiovascular function, with durable responses of up to 2 years in obese patients. Mediterranean diet supplemented with extra-virgin olive oil reduced the incidence of breast cancer compared with a control diet. Physical activity is another important lifestyle factor which may also contribute to reduced systemic biomarkers of metabolic syndrome associated to obesity. In this scenario, precision nutrition may provide complementary approaches to target the metabolic inflammation associated to "unhealthy obesity". Herein, we first describe the different types of adipose tissue -thermogenic active brown adipose tissue (BAT) versus the energy storing white adipose tissue (WAT). We then move on precision nutrition based strategies, by mean of natural extracts derived from plants and/or diet derived ingredients, which may be useful to normalize the metabolic inflammation associated to "unhealthy obesity". More specifically, we focus on two axis: (1) the activation of thermogenesis in BAT and browning of WAT; (2) and the potential of augmenting the oxidative capacity of muscles to dissipate energy. These strategies may be particularly relevant as complementary approaches to alleviate obesity associated effects on chronic inflammation, immunosuppression, angiogenesis and chemotherapy resistance in cancer. Finally, we summarize main studies where plant derived extracts, mainly, polyphenols and flavonoids, have been applied to increase the energy expenditure.

Pomace Olive Oil Concentrated in Triterpenic Acids Restores Vascular Function, Glucose Tolerance and Obesity Progression in Mice.

Pomace olive oil, an olive oil sub-product, is a promising source of bioactive triterpenoids such as oleanolic acid and maslinic acid. Considering the vascular actions of pomace olive oil and the potential effects of the isolated oleanolic acid on metabolic complications of obesity, this study investigates for the first time the dietary intervention with a pomace olive oil with high concentrations of the triterpenic acids (POCTA), oleanolic and maslinic acid, during diet-induced obesity in mice. The results demonstrate that obese mice, when switched to a POCTA-diet for 10 weeks, show a substantial reduction of body weight, insulin resistance, adipose tissue inflammation, and particularly, improvement of vascular function despite high caloric intake. This study reveals the potential of a functional food based on pomace olive oil and its triterpenic fraction against obesity progression. Our data also contribute to understanding the health-promoting effects attributable to the Mediterranean diet.

Low Phytanic Acid-Concentrated DHA Prevents Cognitive Deficit and Regulates Alzheimer Disease Mediators in an ApoE-/- Mice Experimental Model.

Alzheimer's disease (AD) is the main cause of dementia and cognitive impairment. It has been associated with a significant diminution of omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) levels in the brain. Clinical trials with DHA as a treatment in neurological diseases have shown inconsistent results. Previously, we reported that the presence of phytanic acid (PhA) in standard DHA compositions could be blunting DHA's beneficial effects. Therefore, we aimed to analyze the effects of a low PhA-concentrated DHA and a standard PhA-concentrated DHA in Apolipoprotein E knockout (ApoE-/-) mice. Behavioral tests and protein expression of pro-inflammatory, pro-oxidant, antioxidant factors, and AD-related mediators were evaluated. Low PhA-concentrated DHA decreased Aß, ß-amyloid precursor protein (APP), p-tau, Ca2+/calmodulin-dependent protein kinase II (CAMKII), caspase 3, and catalase, and increased brain derived neurotrophic factor (BDNF) when compared to standard PhA-concentrated DHA. Low PhA-concentrated DHA decreased interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) protein expression in ApoE-/- mice when compared to standard PhA-concentrated DHA. No significant differences were found in p22phox, inducible nitric oxide synthase (iNOS), glutathione peroxidase (GPx), superoxide dismutase 1 (SOD-1), and tau protein expression. The positive actions of a low PhA-concentrated DHA were functionally reflected by improving the cognitive deficit in the AD experimental model. Therefore, reduction of PhA content in DHA compositions could highlight a novel pathway for the neurodegeneration processes related to AD.

A Novel Class of Cationic and Non-Peptidic Small Molecules as Hits for the Development of Antimicrobial Agents.

Cationic and non-peptide small molecules containing a total of six positive charges arranged on one side and a long aliphatic tail on the other have been synthesized and tested against Gram-positive and Gram-negative bacteria. The positive charges have been contributed by two aminophenol residues. These molecules have showed remarkable antimicrobial activity against Gram-positive bacteria including multidrug-resistant strains. Our structure⁻activity relationship studies demonstrated the importance of the length and flexibility of the hydrophobic tail for the antimicrobial activity. Importantly, these compounds are non-toxic to eukaryotic cells at the concentration affecting growth in bacteria, reflecting an acceptable margin of safety. The small size and easy synthetic accessibility of our molecules can be of interest for the further development of novel antimicrobials against Gram-positive bacterial pathogens, including multidrug-resistant strains.

Novel Polyphenols That Inhibit Colon Cancer Cell Growth Affecting Cancer Cell Metabolism.

New series of polyphenols with a hydrophilic galloyl-based head and a hydrophobic N-acyl tail, linked through a serinol moiety, have been synthesized and tested against colon cancer cell growth. Our structure activity relationship studies revealed that galloyl moieties are essential for growth inhibition. Moreover, the length of the N-acyl chain is crucial for the activity. Introduction of a (Z) double bond in the acyl chain increased the anticancer properties. Our findings demonstrate that 16, the most potent compound within this series, has inhibitory effects on colon cancer cell growth and metabolism (glycolysis and mitochondrial respiration) at the same time that it activates 5'AMP-activated kinase (AMPK) and induces apoptotic cell death. Based on these results, we propose that 16 might reprogram colon cancer cell metabolism through AMPK activation. This might lead to alterations on cancer cell bioenergy compromising cancer cell viability. Importantly, these antiproliferative and proapoptotic effects are selective for cancer cells. Accordingly, these results indicate that 16, with an unsaturated C18 chain, might be a useful prototype for the development of novel colon cancer cell growth inhibitors affecting cell metabolism.

Effects of Low Phytanic Acid-Concentrated DHA on Activated Microglial Cells: Comparison with a Standard Phytanic Acid-Concentrated DHA.

Docosahexaenoic acid (DHA, 22:6 n-3) is an essential omega-3 (ω-3) long chain polyunsaturated fatty acid of neuronal membranes involved in normal growth, development, and function. DHA has been proposed to reduce deleterious effects in neurodegenerative processes. Even though, some inconsistencies in findings from clinical and pre-clinical studies with DHA could be attributed to the presence of phytanic acid (PhA) in standard DHA treatments. Thus, the aim of our study was to analyze and compare the effects of a low PhA-concentrated DHA with a standard PhA-concentrated DHA under different neurotoxic conditions in BV-2 activated microglial cells. To this end, mouse microglial BV-2 cells were stimulated with either lipopolysaccharide (LPS) or hydrogen peroxide (H2O2) and co-incubated with DHA 50 ppm of PhA (DHA (PhA:50)) or DHA 500 ppm of PhA (DHA (PhA:500)). Cell viability, superoxide anion (O2-) production, Interleukin 6 (L-6), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), glutathione peroxidase (GtPx), glutathione reductase (GtRd), Caspase-3, and the brain-derived neurotrophic factor (BDNF) protein expression were explored. Low PhA-concentrated DHA protected against LPS or H2O2-induced cell viability reduction in BV-2 activated cells and O2- production reduction compared to DHA (PhA:500). Low PhA-concentrated DHA also decreased COX-2, IL-6, iNOS, GtPx, GtRd, and SOD-1 protein expression when compared to DHA (PhA:500). Furthermore, low PhA-concentrated DHA increased BDNF protein expression in comparison to DHA (PhA:500). The study provides data supporting the beneficial effect of low PhA-concentrated DHA in neurotoxic injury when compared to a standard PhA-concentrated DHA in activated microglia.

Olive oil bioactives protect pigs against experimentally-induced chronic inflammation independently of alterations in gut microbiota.

Subclinical chronic inflammation (SCI) is associated with impaired animal growth. Previous work has demonstrated that olive-derived plant bioactives exhibit anti-inflammatory properties that could possibly counteract the growth-depressing effects of SCI. To test this hypothesis and define the underlying mechanism, we conducted a 30-day study in which piglets fed an olive-oil bioactive extract (OBE) and their control counterparts (C+) were injected repeatedly during the last 10 days of the study with increasing doses of Escherichia coli lipopolysaccharides (LPS) to induce SCI. A third group of piglets remained untreated throughout the study and served as a negative control (C-). In C+ pigs, SCI increased the circulating concentration of interleukin 1 beta (p < 0.001) and decreased feed ingestion (p < 0.05) and weight gain (p < 0.05). These responses were not observed in OBE animals. Although intestinal inflammation and colonic microbial ecology was not altered by treatments, OBE enhanced ileal mRNA abundance of tight and adherens junctional proteins (p < 0.05) and plasma recovery of mannitol (p < 0.05) compared with C+ and C-. In line with these findings, OBE improved transepithelial electrical resistance (p < 0.01) in TNF-α-challenged Caco-2/TC-7 cells, and repressed the production of inflammatory cytokines (p < 0.05) in LPS-stimulated macrophages. In summary, this work demonstrates that OBE attenuates the suppressing effect of SCI on animal growth through a mechanism that appears to involve improvements in intestinal integrity unrelated to alterations in gut microbial ecology and function.

Protective effect of a pomace olive oil concentrated in triterpenic acids in alterations related to hypertension in rats: mechanisms involved.

SCOPE: Despite the amount of information and research on the effects of virgin olive oil and its components in cardiovascular disease, little attention has been paid to the effects of pomace olive oil, an olive oil subproduct traditionally used in Spain. The aim of the present study was to evaluate the potential effects of a pomace olive oil concentrated in triterpenic acids (POCTA) on blood pressure, cardiac hemodynamics, and functional and molecular vascular alterations associated with hypertension in spontaneously hypertensive rats (SHR). METHODS AND RESULTS: The study showed that POCTA attenuated the increase of blood pressure in SHR. This effect was associated with an improvement in endothelium-dependent relaxation, enhancement of vascular expression of endothelial nitric oxide synthase, and reduction of tumor necrosis factor alpha, transforming growth factor beta, and collagen I. Furthermore, POCTA improved cardiac hemodynamics (left ventricular systolic pressure and left ventricular end-diastolic pressure) and decreased relative kidney and lung weights. CONCLUSION: POCTA exerts antihypertensive effects together with vascular and hypertension target organ protection in SHR. Since interest in pomace olive oil has been low, the results of this study contribute to increasing awareness of its biological and nutritional values.