Effect of Extra Virgin Olive Oil on Anthropometric Indices, Inflammatory and Cardiometabolic Markers: a Systematic Review and Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: A large body of literature associated extra virgin olive oil (EVOO) consumption with low risk of cardiovascular disease and mortality. However, findings from clinical trials related to EVOO consumption on blood pressure, lipid profile, and anthropometric and inflammation parameters are not univocal. OBJECTIVES: The aim of this systematic review and meta-analysis was to evaluate the effect of EVOO consumption on cardiometabolic risk factors and inflammatory mediators. METHODS: We searched PubMed/MEDLINE, Scopus, and Cochrane up through 31 March, 2023, without any particular language limitations, in order to identify randomized controlled trials (RCTs) that examined the effects of EVOO consumption on cardiometabolic risk factors, inflammatory mediators, and anthropometric indices. Outcomes were summarized as standardized mean difference (SMD) with 95% confidence intervals (CIs) estimated from Hedge's g and random-effects modeling. Heterogeneity was assessed by Cochran Q-statistic and quantified (I2). RESULTS: Thirty-three trials involving 2020 participants were included. EVOO consumption was associated with a significant decrease in insulin (n = 10; SMD: -0.28; 95% CI: -0.51, -0.05; I2 = 48.57%) and homeostasis model assessment of insulin resistance levels (HOMA-IR) (n = 9; SMD: -0.19; 95% CI: -0.35, -0.03; I2 = 00.00%). This meta-analysis indicated no significant effect of consuming EVOO on fasting blood glucose, triglycerides, total cholesterol, low density lipoproteins, very low density lipoproteins, high density lipoproteins, Apolipoprotein (Apo) A-I and B, lipoprotein a, blood pressure, body mass index, waist circumference, waist to hip ratio, C-reactive protein, interleukin-6, interleukin-10, and tumor necrosis factor α levels (P > 0.05). CONCLUSIONS: The present evidence supports a beneficial effect of EVOO consumption on serum insulin levels and HOMA-IR. However, larger well-designed RCTs are still required to evaluate the effect of EVOO on cardiometabolic risk biomarkers. This study was registered in PROSPERO as CRD42023409125.

Effect of glycated HDL on oxidative stress and cholesterol homeostasis in a human bladder cancer cell line, J82.

Epidemiological studies suggest associations between diabetes mellitus (DM) andbladder cancer. Several potential mechanisms may explain the increased bladdercancer burden in DM patients. Hyperglycaemia is associated with dysregulation of cellintracellular metabolism and alterations of lipoprotein metabolism and oxidative stress. Dysfunctional HDL including glycated and oxidized HDL are described in DM. Weevaluated the effect of normal HDL (N-HDL) and glycated HDL (G-HDL) on cellproliferation and oxidative stress of J82 bladder cancer cells. We also studied the effectof HDL on cholesterol influx and efflux. In addition, the levels of proteins involvedin cholesterol transport (ABCA1, SRB1, ABCG1) by western blot analysis were studied.Our results demonstrate that N-HDL and G-HDL promote cell proliferation and increase intracellular reactive oxygen species (ROS) levels triggered by incubation of tert-butylhydroperoxide. The increase of intracellular ROS in cells preincubated with G-HDL was associated to higher levels of TBARS in cells compared to N-HDL. Cholesterol efflux wasincreased, on the contrary cholesterol influx was significantly decreased in cellsincubated with G-HDL with respect to cells incubated with N-HDL. Levels of SR-B1 and ABCG1 was increased in cells incubated with G-HDL, suggestingthat dysfunctional HDL could affect cholesterol homeostasis in J82 cells. These resultssuggest that HDL-based treatments should be considered for treatment of urinary bladder cancer.

The role of paraoxonase 1 in regulating high-density lipoprotein functionality during aging.

Pharmacological interventions to increase the concentration of high-density lipoprotein (HDL) have led to disappointing results and have contributed to the emergence of the concept of HDL functionality. The anti-atherogenic activity of HDLs can be explained by their functionality or quality. The capacity of HDLs to maintain cellular cholesterol homeostasis and to transport cholesterol from peripheral cells to the liver for elimination is one of their principal anti-atherogenic activities. However, HDLs possess several other attributes that contribute to their protective effect against cardiovascular diseases. HDL functionality is regulated by various proteins and lipids making up HDL particles. However, several studies investigated the role of paraoxonase 1 (PON1) and suggest a significant role of this protein in the regulation of the functionality of HDLs. Moreover, research on PON1 attracted much interest following several studies indicating that it is involved in cardiovascular protection. However, the mechanisms by which PON1 exerts these effects remain to be elucidated.

Advanced glycation end products affect cholesterol homeostasis by impairing ABCA1 expression on macrophages.

Reverse cholesterol transport (RCT), which is intimately linked to high-density lipoproteins (HDLs), plays a key role in cholesterol homeostasis and the prevention of atherosclerosis. The goal of the present study was to investigate the effect of aging and advanced glycation end products (AGEs) on RCT as well as on other factors that may affect the antiatherogenic property of HDLs. The transfer of macrophage-derived cholesterol to the plasma and liver and then to the feces for elimination was significantly lower in aged mice than in young mice. Chronic injection of d -galactose (D-gal) or AGEs also significantly reduced RCT (65.3% reduction in [3H]cholesterol levels in the plasma of D-gal-treated mice after 48 h compared with control mice, P < 0.01). The injection of both D-gal and aminoguanidine hydrochloride increased [3H]cholesterol levels in the plasma, although the levels were lower than those of control mice. The in vitro incubation of HDLs with dicarbonyl compounds increased the carbonyl and conjugated diene content of HDLs and significantly reduced PON1 paraoxonase activity (87.4% lower than control HDLs, P < 0.0001). Treating J774A.1 macrophages with glycated fetal bovine serum increased carbonyl formation (39.5% increase, P < 0.003) and reduced ABCA1 protein expression and the capacity of macrophages to liberate cholesterol (69.1% decrease, P < 0.0001). Our results showed, for the first time, that RCT is altered with aging and that AGEs contribute significantly to this alteration.

Alteration of high-density lipoprotein functionality in Alzheimer's disease patients.

The aims of the present study were to determine whether high-density lipoprotein (HDL) functionality-mediated cholesterol efflux is altered in Alzheimer's disease and to investigate the role and effect of amyloid-beta (Aß) in the regulation of the anti-atherogenic activity of HDL. Eighty-seven elderly subjects were recruited, of whom 27 were healthy, 27 had mild cognitive impairment (MCI), and 33 had mild Alzheimer's disease (mAD). Our results showed that total cholesterol levels are negatively correlated with the Mini-Mental State Examination (MMSE) score (r = -0.2602, p = 0.0182). HDL from the mAD patients was less efficient at mediating cholesterol efflux from J774 macrophages (p < 0.05) than HDL from the healthy subjects and MCI patients. While HDL from the MCI patients was also less efficient at mediating cholesterol efflux than HDL from the healthy subjects, the difference was not significant. Interestingly, the difference between the healthy subjects and the MCI and mAD patients with respect to the capacity of HDL to mediate cholesterol efflux disappeared when ATP-binding cassette transporter A1 (ABCA1)-enriched J774 macrophages were used. HDL fluidity was significantly inversely correlated with the MMSE scores (r = -0.4137, p < 0.009). In vitro measurements of cholesterol efflux using J774 macrophages showed that neither Aß1-40 nor Aß1-42 stimulate cholesterol efflux from unenriched J774 macrophages in basal or ABCA1-enriched J774 macrophages.

High-Density Lipoprotein Metabolism and Function in Cardiovascular Diseases: What about Aging and Diet Effects?

Cardiovascular diseases (CVDs) have become the leading global cause of mortality, prompting a heightened focus on identifying precise indicators for their assessment and treatment. In this perspective, the plasma levels of HDL have emerged as a pivotal focus, given the demonstrable correlation between plasma levels and cardiovascular events, rendering them a noteworthy biomarker. However, it is crucial to acknowledge that HDLs, while intricate, are not presently a direct therapeutic target, necessitating a more nuanced understanding of their dynamic remodeling throughout their life cycle. HDLs exhibit several anti-atherosclerotic properties that define their functionality. This functionality of HDLs, which is independent of their concentration, may be impaired in certain risk factors for CVD. Moreover, because HDLs are dynamic parameters, in which HDL particles present different atheroprotective properties, it remains difficult to interpret the association between HDL level and CVD risk. Besides the antioxidant and anti-inflammatory activities of HDLs, their capacity to mediate cholesterol efflux, a key metric of HDL functionality, represents the main anti-atherosclerotic property of HDL. In this review, we will discuss the HDL components and HDL structure that may affect their functionality and we will review the mechanism by which HDL mediates cholesterol efflux. We will give a brief examination of the effects of aging and diet on HDL structure and function.

High Tyrosol and Hydroxytyrosol Intake Reduces Arterial Inflammation and Atherosclerotic Lesion Microcalcification in Healthy Older Populations.

Aging is an important risk factor for cardiovascular diseases and convincing data have shown that chronic low-grade inflammation, which develops with advanced age, contributes significantly to cardiovascular risk. The present study aimed to use 18F-FDG/18F-NaF-PET/CT imaging to, respectively, gauge arterial inflammation and microcalcification in a healthy elderly population and to assess the potential benefits of a tyrosol- and hydroxytyrosol-rich diet on these two markers of atherosclerotic plaque fragility. Eleven healthy participants (mean age 75 ± 5.67 years) were supplemented for 6 months with high polyphenol-rich extra virgin olive oil (HP-EVOO), extra virgin olive oil (EVOO), or refined olive oil (ROO). The participants underwent PET/CT imaging with 18F-FDG and 18F-NaF radiotracers at baseline and after 6 months. 18F-FDG and 18F-NaF uptakes were quantified using standardized uptake values (SUV) and were categorized based on artery calcification and olive oil type. A total of 324 slices of the aortas of the imaged participants were analyzed for arterial inflammation and 327 slices were analyzed for microcalcification. 18F-FDG uptake was significantly higher in the non-calcified segments than in the calcified segments (SUVmax = 2.70 ± 0.62 and SUVmax = 2.54 ± 0.44, respectively, p < 0.042). Conversely, the non-calcified segments displayed significantly lower 18F-NaF uptake than the calcified segments (SUVmax = 1.90 ± 0.37 and 2.09 ± 0.24, respectively, p < 0.0001). The 6-month supplementation with HP-EVOO induced a significant reduction in 18F-FDG uptake in both the non-calcified (2.93 ± 0.23 to 2.75 ± 0.38, p < 0.004) and calcified segments of the aortas (2.25 ± 0.29 to 2.15 ± 0.19, p < 0.02). 18F-NaF uptake was also significantly lower in patients supplemented with HP-EVOO (SUVmax = 1.98 ± 0.33 at baseline compared to 1.85 ± 0.28, after the 6-month supplementation, p < 0.004), whereas no significant effect was observed with EVOO. Conversely, participants supplemented with ROO displayed a significant increase in 18F-NaF uptake (SUVmax = 1.78 ± 0.34 to 1.95 ± 0.34, p < 0.0001). The present study confirmed that a phenolic-compound-rich diet reduces both arterial inflammation and atherosclerotic lesion microcalcification and demonstrated that 18F-FDG/18F-NaF-PET/CT imaging is a valuable approach for assessing age-related arterial damage.

Extra-virgin olive oil consumption improves the capacity of HDL to mediate cholesterol efflux and increases ABCA1 and ABCG1 expression in human macrophages.

The present study was aimed to investigate the effect of 12 weeks of extra-virgin olive oil (EVOO) consumption on the capacity of HDL to promote cholesterol efflux (CE) and to determine which CE pathways are modulated by EVOO consumption. Whole HDL and HDL2/HDL3 subclasses were isolated from the plasma of twenty-six healthy volunteers before and after 12 weeks of EVOO consumption (25 ml/d). EVOO consumption increased the capacity of serum and HDL to mediate CE from THP-1, J774 macrophages and Fu5AH cells by 9·8-24·57 %, depending on the cell type. The increase in CE was independent of both HDL concentration and subclass distribution. The three HDL-mediated CE pathways (ATP-binding cassette (ABC) A1, ABCG1 and scavenger receptor class B type I (SR-BI)) were modulated by EVOO consumption. The fluidity of the phospholipidic layer of HDL increased by 13 % (P< 0·001) following EVOO consumption compared with baseline. EVOO consumption also increased the release of excess cholesterol from human monocyte-derived macrophages (HMDM) by 44 % (P< 0·001), and ABCA1 and ABCG1 mRNA transcription by 16·08 % (P< 0·001) and 35·79 % (P< 0·01), respectively. The protein expression of these two cholesterol transporters also increased after EVOO consumption. In contrast, SR-BI mRNA and protein expression in HMDM were significantly lower after 12 weeks of EVOO consumption. Incubating J774 macrophages with EVOO polyphenol extracts induced a concentration-dependent up-regulation of ABCA1 and ABCG1 expression in macrophages. After 12 weeks of EVOO consumption, the capacity of HDL to mediate CE was improved and the ability of HMDM to release excess cholesterol was enhanced by increasing the expression of ABCA1 and ABCG1 transporters.

Extra-virgin olive oil consumption reduces the age-related decrease in HDL and paraoxonase 1 anti-inflammatory activities.

Paraoxonase 1 (PON1) is associated with HDL and modulates the antioxidant and anti-inflammatory role of HDL. The goals of the present study were to investigate the effect of ageing and the role of PON1 on the anti-inflammatory activity of HDL, and to determine whether extra-virgin olive oil (EVOO) consumption could improve the atheroprotective activity of HDL. HDL and PON1 were isolated from the plasma of ten young (Y-HDL and Y-PON1) and ten elderly (E-HDL and E-PON1) healthy volunteers before and after 12 weeks of EVOO consumption. Inflammation was assessed by measuring intracellular adhesion molecule 1 (ICAM-1) expression. THP-1 (human acute monocytic leukaemia cell line) monocyte chemotaxis was measured using a Boyden chamber. Oxidative damage to HDL was assessed by measuring conjugated diene formation and changes in electrophoretic migration. Y-HDL had more anti-inflammatory activity than E-HDL. The conjugated diene content and the electrophoretic mobility of E-HDL were higher than those of Y-HDL. Y-PON1 had significant anti-inflammatory activity, reducing ICAM-1 expression by 32·64 (SD 2·63)%, while E-PON1 had no significant effect. THP-1 chemotaxis measurements confirmed the ICAM-1 expression results. The 12 weeks of EVOO consumption significantly increased the anti-inflammatory activities of both HDL and PON1. The anti-inflammatory activity of HDL was modulated by PON1 and was lower in the elderly volunteers. EVOO consumption increased the anti-inflammatory effect of HDL and reduced the age-related decrease in anti-atherogenic activity.

Effects of vegetable oils on biochemical and biophysical properties of membrane retinal pigment epithelium cells.

The aim of this study was to investigate the effect of vegetable oil enrichment of retinal pigment epithelial (RPE) cells on their biochemical and biophysical properties. For this, RPE cells were incubated with 4 different vegetables oils (olive oil, corn oil, argan oil, and camelina oil). The cytotoxicity of these vegetable oils was assessed in vivo on 8-week-old mice and in vitro by using the neutral red and YO-PRO-1 tests. Membrane fluidity was evaluated by fluorescence anisotropy using the fluorescent probe diphenylhexatriene, and membrane fatty acid composition was assessed by gas chromatography. None of the oils tested displayed cytotoxic effects. In vitro, omega-3 rich oils improved membrane fluidity by 47% compared with the control cells. The omega-3 PUFA content within membranes decreased by 38% to 55% when cells were incubated separately with olive oil, corn oil, or argan oil, and increased when cells were incubated with a mixture of those oils, or with camelina oil alone (50% and 103% increase, respectively). Our results show that the fatty acids in vegetable oil incorporate into retinal cells and increase the plasma membrane fluidity.

Small Dense LDL Level and LDL/HDL Distribution in Acute Coronary Syndrome Patients.

This study aimed to determine the size and distribution of LDL and HDL particles in North African acute coronary syndrome (ACS) patients and to compare the level of small dense LDL (sdLDL) to other markers used in cardiovascular risk prediction. METHODS: A total of 205 ACS patients and 100 healthy control subjects were enrolled. LDL particle size and LDL and HDL subclass distributions were measured using Quantimetric Lipoprint® linear polyacrylamide gel electrophoresis. Lipid ratios (total cholesterol, LDL cholesterol, non-HDL cholesterol, and HDL cholesterol) were determined to calculate the atherogenic index of plasma (AIP), the atherogenic coefficient (AC), Castelli's Risk-I (CR-I), and Castelli's Risk-II (CR-II). Receiver operating characteristic (ROC) curve analyses and area under the curve (AUC) were used to assess the predictive value of sdLDL as a marker for cardiovascular disease. RESULTS: The ACS patients, compared to the healthy control subjects, displayed an alteration of LDL particle distribution, with a significant increase in sdLDL serum concentrations (0.303 ± 0.478 mmol/L vs. 0.0225 ± 0.043 mmol/L, respectively, p < 0.001). The sdLDL levels had a high discrimination accuracy [AUC = 0.847 ± 0.0353 (95% CI 0.778 to 0.916, p < 0.0001)]. The best predictive cutoff value of ACS determined with the maximum Youden index (J) [(sensitivity + specificity) - 1 = 0.60] was 0.038 mmol/L. A Spearman correlation analysis showed that sdLDL levels were moderately but significantly and positively correlated with AC and CR-I (r = 0.37, p < 0.001) and weakly but significantly correlated with PAI and CR-II; r = 0.32 (p < 0.001) and r = 0.30 (p < 0.008), respectively. The subclass distribution of HDL particles from ACS patients was also altered, with a decrease in large HDL particles and an increase in small HDL particles compared to HDL from healthy control subjects. CONCLUSION: Due to their high atherogenicity, sdLDL levels could be used as a valuable marker for the prediction cardiovascular events.

The Modulatory Bioeffects of Pomegranate (Punica granatum L.) Polyphenols on Metabolic Disorders: Understanding Their Preventive Role against Metabolic Syndrome.

Modern research achievements support the health-promoting effects of natural products and diets rich in polyphenols. Pomegranate (PG) (Punica granatum L.) contains a considerable number of bioactive compounds that exert a broad spectrum of beneficial biological activities, including antimicrobial, antidiabetic, antiobesity, and atheroprotective properties. In this context, the reviewed literature shows that PG intake might reduce insulin resistance, cytokine levels, redox gene expression, blood pressure elevation, vascular injuries, and lipoprotein oxidative modifications. The lipid parameter corrective capabilities of PG-ellagitannins have also been extensively reported to be significantly effective in reducing hyperlipidemia (TC, LDL-C, VLDL-C, and TAGs), while increasing plasma HDL-C concentrations and improving the TC/HDL-C and LDL-C/HDL-C ratios. The health benefits of pomegranate consumption seem to be acheived through the amelioration of adipose tissue endocrine function, fatty acid utilization, GLUT receptor expression, paraoxonase activity enhancement, and the modulation of PPAR and NF-κB. While the results from animal experiments are promising, human findings published in this field are inconsistent and are still limited in several aspects. The present review aims to discuss and provide a critical analysis of PG's bioeffects on the components of metabolic syndrome, type-2 diabetes, obesity, and dyslipidemia, as well as on certain cardiovascular-related diseases. Additionally, a brief overview of the pharmacokinetic properties, safety, and bioavailability of PG-ellagitannins is included.

Role of Paraoxonase1 in the Regulation of High-Density Lipoprotein Functionality and in Cardiovascular Protection.

Significance: Human paraoxonase (PON) is a member of the gene family that includes paraoxonase 1 (PON1), PON2, and PON3. PON is known for its capacity to hydrolyze a wide range of substrates, including organophosphorus compounds, nerve gases, and aromatic carboxylic acid esters. Recent Advances: Several studies have highlighted the involvement of PON, particularly PON1, in the modulation of the capacity of high-density lipoprotein (HDL) to protect against the atherosclerosis process and its clinical manifestations. PON1 exhibits antioxidant and anti-inflammatory activities and may be involved in the regulation of the principal antiatherogenic activity of HDL, that is, the regulation of the reverse cholesterol transport process. Critical Issues: Although epidemiological studies have shown that there is an inverse relationship between HDL levels and cardiovascular risk, several studies have emphasized the importance of HDL functionality in protecting against cardiovascular diseases (CVD). Given that PON1 is involved in several atheroprotective functions of HDL, the aim of this article is to review the existing literature on PON1 and to discuss the principal mechanisms by which PON1 may exert its different activities. Future Directions: The elucidation of the mechanisms by which PON1 modulates the functionality of HDL as well as the identification of the interventions that stimulate PON1 activity and/or increase its plasma concentration would make it possible to propose new strategies to prevent CVD. Antioxid. Redox Signal. 34, 191-200.

The Susceptibility to Diet-Induced Atherosclerosis Is Exacerbated with Aging in C57B1/6 Mice.

The anti-atherogenic activity of HDL is mainly due to their capacity to mediate reverse cholesterol transport (RCT). However, it is not clear to what extent this activity is affected by aging or pro-atherogenic conditions. Three and 24-month-old C57Bl/6 mice were fed an atherogenic diet (high fat, high cholesterol) for 12 weeks. The aged mice displayed a significant reduction in the capacity of HDL to mediate RCT (29.03%, p < 0.0006). Interestingly, the atherogenic diet significantly stimulated the RCT process in both young and aged mice (241% and 201%, respectively, p < 0.01). However, despite this, significant amounts of cholesterol accumulated in the aortas of mice fed an atherogenic diet as compared to regular chow. The accumulation of cholesterol was more marked in the aortas of aged mice (110% increase, p < 0.002). ABCA1 and ABCG1 protein expression on macrophages decreased significantly (52 to 37% reduction, p < 0.002), whereas their expression on hepatic cells increased significantly (up to 590% for ABCA1 and 116% for ABCG1, p < 0.002). On the other hand, SR-BI protein expression on hepatic cells decreased significantly (42.85%, p < 0.0001). ABCG5, ABCG8, and CYP7a protein expression on hepatic cells was also higher in mice fed an atherogenic diet. The increase was age-dependent for both ABCG5 and ABCG8. Our results suggest that the susceptibility to diet-induced atherosclerosis is exacerbated with aging and is a consequence of the dysregulation of the expression levels of membrane cholesterol transporters.

Extra Virgin Olive Oil Prevents the Age-Related Shifts of the Distribution of HDL Subclasses and Improves Their Functionality.

High-density lipoproteins (HDL) maintain cholesterol homeostasis through the role they play in regulating reverse cholesterol transport (RCT), a process by which excess cholesterol is transported back to the liver for elimination. However, RCT can be altered in the presence of cardiovascular risk factors, such as aging, which contributes to the increase in the incidence of cardiovascular diseases (CVD). The present study was aimed at investigating the effect of extra virgin olive oil (EVOO) intake on the cholesterol efflux capacity (CEC) of HDL, and to elucidate on the mechanisms by which EVOO intake improves the anti-atherogenic activity of HDL. A total of 84 healthy women and men were enrolled and were distributed, according to age, into two groups: 27 young (31.81 ± 6.79 years) and 57 elderly (70.72 ± 5.6 years) subjects. The subjects in both groups were given 25 mL/d of extra virgin olive oil (EVOO) for 12 weeks. CEC was measured using J774 macrophages radiolabeled with tritiated cholesterol ((3H) cholesterol). HDL subclass distributions were analyzed using the Quantimetrix Lipoprint® system. The HDL from the elderly subjects exhibited a lower level of CEC, at 11.12% (p < 0.0001), than the HDL from the young subjects. The CEC of the elderly subjects returned to normal levels following 12 weeks of EVOO intake. An analysis of the distribution of HDL subclasses showed that HDL from the elderly subjects were composed of lower levels of large HDL (L-HDL) (p < 0.03) and higher levels of small HDL (S-HDL) (p < 0.002) compared to HDL from the young subjects. A multiple linear regression analysis revealed a positive correlation between CEC and L-HDL levels (r = 0.35 and p < 0.001) as well as an inverse correlation between CEC and S-HDL levels (r = -0.27 and p < 0.01). This correlation remained significant even when several variables, including age, sex, and BMI as well as low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and glucose levels (ß = 0.28, p < 0.002, and ß = 0.24, p = 0.01) were accounted for. Consuming EVOO for 12 weeks modulated the age-related difference in the distribution of HDL subclasses by reducing the level of S-HDL and increasing the level of intermediate-HDL/large-HDL (I-HDL/L-HDL) in the elderly subjects. The age-related alteration of the CEC of HDL was due, in part, to an alteration in the distribution of HDL subclasses. A diet enriched in EVOO improved the functionality of HDL through an increase in I-HDL/L-HDL and a decrease in S-HDL.

Synergistic effect of Pseudomonas alkylphenolica PF9 and Sinorhizobium meliloti Rm41 on Moroccan alfalfa population grown under limited phosphorus availability.

This study looked at the synergistic effect of Pseudomonas alkylphenolica PF9 and Sinorhizobium meliloti Rm41 on the Moroccan alfalfa population (Oued Lmaleh) grown under symbiotic nitrogen fixation and limited phosphorus (P) availability. The experiment was conducted in a growth chamber and after two weeks of sowing, the young seedlings were inoculated with Sinorhizobium meliloti Rm41 alone or combined with a suspension of Pseudomonas alkylphenolica PF9. Then, the seedlings were submitted to limited available P (insoluble P using Ca3HPO4) versus a soluble P form (KH2PO4) at a final concentration of 250 µmol P·plant-1·week-1. After two months of P stress, the experiment was evaluated through some agro-physiological and biochemical parameters. The results indicated that the inoculation of alfalfa plants with Sinorhizobium strain alone or combined with Pseudomonas strain significantly (p < 0.001) improved the plant growth, the physiological and the biochemical traits focused in comparison to the uninoculated and P-stressed plants. For most sets of parameters, the improvement was more obvious in plants co-inoculated with both strains than in those inoculated with Sinorhizobium meliloti Rm41 alone. In fact, under limited P-availability, the co-inoculation with two strains significantly (p < 0.01) enhanced the growth of alfalfa plants evaluated by fresh and dry biomasses, plant height and leaf area. The results indicated also that the enhancement noted in plant growth was positively correlated with the shoot and root P contents. Furthermore, the incensement in plant P contents in response to bacterial inoculation improved cell membrane stability, reflected by low malonyldialdehyde (MDA) and electrolyte leakage (EL) contents, and photosynthetic-related parameters such as chlorophyll contents, the maximum quantum yield of PS II (Fv/Fm) and stomatal conductance (gs). Our findings suggest that Pseudomonas alkylphenolica PF9 can act synergistically with Sinorhizobium meliloti Rm41 in promoting alfalfa growth under low-P availability.

Antioxidant Effect of Moroccan Pomegranate (Punica granatum L. Sefri Variety) Extracts Rich in Punicalagin against the Oxidative Stress Process.

Natural antioxidants products are widely distributed in food and medicinal plants. These natural antioxidants, especially polyphenols, exhibit a wide range of biological activities including anti-cancer, anti-inflammatory, and anti-atherosclerosis activities. Pomegranate (Punica granatum L.) is a rich source of polyphenolic components. The purpose of this study was to characterize the phenolic composition and flavonoids and anthocyanin content of different parts (peel and aril) of the Sefri variety of pomegranate. Our results showed that Peel extract was richer in these compounds than that of the Arils, especially in Punicalagin (A and B). DPPH free radical scavenging, reducing power (FRAP), ß-carotene bleaching, and hydrogen peroxide scavenging assays revealed a greater dose-dependent activity of pomegranate peel phenolic extract (PPPE) compared to pomegranate aril phenolic extract (PAPE). PPPE was also more potent than PAPE concerning its ability to inhibit conjugated diene formation and to reduce α-tocopherol disappearance induced by CuSO4-mediated LDL peroxidation. Interestingly, both extracts (PPPE and PAPE) significantly inhibited lipid peroxidation and the formation of reactive oxygen species (ROS) in stressed J82 human bladder cancer cells. These results reflect the protective effects that this Moroccan variety of pomegranate can provide against the development of metabolic disorder, cancer, atherosclerosis, and cardiovascular disease. Given these properties, further studies should be undertaken to investigate possible applications of Sefri pomegranate extracts in the fields of food preservation and health supplements.

Effect of PON1 polymorphism on HDL antioxidant potential is blunted with aging.

Paraoxonase1 is a HDL-associated enzyme, which is responsible for their antioxidant property. This study was aimed to investigate the effect of PON1 [Q192R] and [L55M] genotypes on susceptibility of LDL and HDL to lipid peroxidation and on antioxidant activity of HDL as a function of aging. Seventy-eight healthy subjects distributed in two age groups, young (20-30 years) and elderly (60-89 years) were recruited. PON1 activities and genotype polymorphisms were determined for each subject. LDL and HDL susceptibility to lipid peroxidation was evaluated by the measure of lag-phase (LP) for conjugated diene formation. HDL antioxidant property was evaluated by the measure of their capacity to protect LDL against lipid peroxidation. Our results show that LP for LDL and HDL peroxidation decreased with age of donors. Moreover, PON1 genotypes affect significantly the susceptibility of LDL and HDL to lipid peroxidation. Furthermore, basal- and salt-stimulated paraoxonase as well arylesterase activities were significantly reduced in elderly compared to young subjects. These results show a beneficial effect of PON1 towards susceptibility of HDL to oxidation as well to their antioxidant effect. However, this PON1 protective effect seems to be blunted with advancing age. Altogether our results suggest that the decrease in the PON1 protective effect with aging may contribute to the acceleration of the atherosclerosis process in elderly.

Human paraoxonase 1 overexpression in mice stimulates HDL cholesterol efflux and reverse cholesterol transport.

This study was aimed to investigate the effect of human PON1 overexpression in mice on cholesterol efflux and reverse cholesterol transport. PON1 overexpression in PON1-Tg mice induced a significant 3-fold (p<0.0001) increase in plasma paraoxonase activity and a significant ~30% (p<0.0001) increase in the capacity of HDL to mediate cholesterol efflux from J774 macrophages compared to wild-type mice. It also caused a significant 4-fold increase (p<0.0001) in the capacity of macrophages to transfer cholesterol to apoA-1, a significant 2-fold (p<0.0003) increase in ABCA1 mRNA and protein expression, and a significant increase in the expression of PPARγ (p<0.0003 and p<0.04, respectively) and LXRα (p<0.0001 and p<0.01, respectively) mRNA and protein compared to macrophages from wild-type mice. Moreover, transfection of J774 macrophages with human PON1 also increased ABCA1, PPARγ and LXRα protein expression and stimulates macrophages cholesterol efflux to apo A1. In vivo measurements showed that the overexpression of PON1 significantly increases the fecal elimination of macrophage-derived cholesterol in PON1-Tg mice. Overall, our results suggested that the overexpression of PON1 in mice may contribute to the regulation of the cholesterol homeostasis by improving the capacity of HDL to mediate cholesterol efflux and by stimulating reverse cholesterol transport.

Phenolic-extract from argan oil (Argania spinosa L.) inhibits human low-density lipoprotein (LDL) oxidation and enhances cholesterol efflux from human THP-1 macrophages.

Argan oil is rich in unsaturated fatty acids, tocopherol and phenolic compounds. These protective molecules make further study of its cardiovascular diseases (CVDs) action interesting. Furthermore, no previous study has explored the antioxidant activity of argan oil in comparison with olive oil. The present study was conducted to evaluate the beneficial properties of Virgin argan oil phenolic extracts (VAO-PE) towards CVD by: (A) protecting human (low-density lipoprotein, LDL) against lipid peroxidation and (B) promoting high-density lipoprotein (HDL)-mediated cholesterol efflux. Human LDLs were oxidized by incubation with CuSO(4) in the presence of different concentrations of VAO-PE (0-320mug/ml). LDL lipid peroxidation was evaluated by conjugated diene and MDA formation as well as Vitamin E disappearance. Incubation of LDL with VAO-PE significantly prolonged the lag-phase and lowered the progression rate of lipid peroxidation (P<0.01) and reduced the disappearance of Vitamin E in a concentration-dependent manner. Incubation of HDL with VAO-PE significantly increased the fluidity of the HDL phospholipidic bilayer (P=0.0004) and HDL-mediated cholesterol efflux from THP-1 macrophages. These results suggest that Virgin argan oil provides a source of dietary phenolic antioxidants, which prevent cardiovascular diseases by inhibiting LDL-oxidation and enhancing reverse cholesterol transport. These properties increase the anti-atherogenic potential of HDL.