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Foods (Basel, Switzerland) Jan 2022Millions of people worldwide are affected by neurodegenerative diseases (NDs). NDs are characterized by progressive damage and death of nerve cells accompanied by high... (Review)
Review
Millions of people worldwide are affected by neurodegenerative diseases (NDs). NDs are characterized by progressive damage and death of nerve cells accompanied by high levels of inflammatory biomarkers and oxidative stress conditions. Punicic acid, the main bioactive component of pomegranate () seed oil, is an omega-5 isomer of conjugated α-linoleic acid that has shown strong anti-oxidative and anti-inflammatory effects that contributes towards its positive effect against a wide arrange of diseases. Punicic acid decreases oxidative damage and inflammation by increasing the expression of peroxisome proliferator-activated receptors. In addition, it can reduce beta-amyloid deposits formation and tau hyperphosphorylation by increasing the expression of GLUT4 protein and the inhibition of calpain hyperactivation. Microencapsulated pomegranate, with high levels of punicic acid, increases antioxidant PON1 activity in HDL. Likewise, encapsulated pomegranate formulations with high levels of punicic acid have shown an increase in the antioxidant PON1 activity in HDL. Because of the limited brain permeability of punicic acid, diverse delivery formulations have been developed to enhance the biological activity of punicic acid in the brain, diminishing neurological disorders symptoms. Punicic acid is an important nutraceutical compound in the prevention and treatment of neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's disease.
PubMed: 35159404
DOI: 10.3390/foods11030252 -
Biomedicine & Pharmacotherapy =... Jun 2023Cardiac fibrosis is a pathological process characterized by an excessive deposition of extracellular matrix (ECM) and an increased production of fibrillar collagen in...
Cardiac fibrosis is a pathological process characterized by an excessive deposition of extracellular matrix (ECM) and an increased production of fibrillar collagen in the cardiac interstitium, mainly caused by the activation of cardiac fibroblasts and their transition into myofibroblasts. Oxidative stress is deeply implicated in the pathogenesis of cardiac fibrosis both directly and via its involvement in the tumor growth factor β1 (TGF-β1) signaling. Ellagic acid (EA) and punicic acid (PA) are the main components of the Punica granatum L (pomegranate) fruit and seed oil respectively, whose antioxidant, anti-inflammatory and anti-fibrotic effects have been previously described. Therefore, the aim of this study was to investigate the effects of EA or PA or EA+PA in an in vitro model of cardiac fibrosis. Immortalized Human Cardiac Fibroblasts (IM-HCF) were stimulated with 10 ng/ml of TGF-β1 for 24 h to induce a fibrotic damage. Cells were then treated with EA (1 µM), PA (1 µM) or EA+PA for additional 24 h. Both EA and PA reduced the pro-fibrotic proteins expressions and the intracellular reactive oxygen species (ROS) accumulation. The anti-oxidant activity was also observed by Nrf2 activation with the consequent TGF-β1-Smad2/3-MMP2/9 and Wnt/β-catenin signaling inhibition, thus reducing collagen production. EA and PA significantly inhibit NF-κB pathway and, consequently, TNF-α, IL-1β and IL-6 levels: the greater effect was observed when EA and PA were used in combination. These results suggest that EA, PA and in particular EA+PA might be effective in reducing fibrosis through their antioxidant and anti-inflammatory properties by the modulation of different molecular pathways.
Topics: Humans; Antioxidants; Transforming Growth Factor beta1; Fibrosis; Anti-Inflammatory Agents; Ellagic Acid
PubMed: 37030134
DOI: 10.1016/j.biopha.2023.114666 -
Lipids in Health and Disease May 2017Punicic acid, a bioactive compound of pomegranate seed oil has gained wide attention for their therapeutic potential. Different studies conducted on animal and human... (Review)
Review
Punicic acid, a bioactive compound of pomegranate seed oil has gained wide attention for their therapeutic potential. Different studies conducted on animal and human models have revealed that punicic acid is very effective against various chronic diseases. Substantial laboratory works has been carried out to elaborate punicic acid effectiveness and mechanism of action in animals. The intention of this review article is to explore the facts about the clinical trials of punicic acid and to discuss different future strategies that can be employed to use it in human clinical trials. Although punicic acid may represent a novel therapeutic unconventional approach for some disorders, still further experimental studies are required to demonstrate its effects in human beings.
Topics: Antioxidants; Fatty Acids; Humans; Linoleic Acids, Conjugated; Linolenic Acids; Metabolic Syndrome
PubMed: 28558700
DOI: 10.1186/s12944-017-0489-3 -
Lipids in Health and Disease Feb 2016This study evaluated the effect of pomegranate seed oil (PSO) supplementation, rich in punicic acid (55 %/C18:3-9c,11 t,13c/CLNA), on the lipid profile and on the...
BACKGROUND
This study evaluated the effect of pomegranate seed oil (PSO) supplementation, rich in punicic acid (55 %/C18:3-9c,11 t,13c/CLNA), on the lipid profile and on the biochemical and oxidative parameters in the gastrocnemius muscle and adipose tissues of healthy rats. Linseed oil (LO), rich in linolenic acid (52 %/C18:3-9c12c15c/LNA) was used for comparison.
METHODS
Male Wistar rats (n = 56) were distributed in seven groups: control (water); LNA 1 %, 2 % and 4 % (treated with LO); CLNA 1 %, 2 % and 4 % (treated with PSO), po for 40 days. The percentages were compared to the daily feed intake. Fatty acid profile were performed by gas chromatography, antioxidant enzymes activity by spectrophotometer and the adipocytes were isolated by collagenase tissue digestion. Analysis of variance (ANOVA) was applied to check for differences between the groups (control, LNAs and CLNAs) and principal component analysis (PCA) was used to project the groups in the factor-place (PC1 vs PC2) based on the biochemical responses assessed in the study.
RESULTS
The fatty acids profile of tissues showed that the LNA percentages were higher in the animals that were fed LO. However, PA was only detected in the adipose tissues. Conjugated linoleic acid (CLA) was present in all the tissues of the animals supplemented with PSO, in a dose dependent manner, and 9c11t-CLA was the predominant isomer. Nevertheless there were no changes in the total weight gain of the animals, the weights of the tissues, and the oxidative stress parameters in the muscle. In addition, there was an increase in the size of the epididymal fat cells in the groups treated with PSO. Principal component analysis (PCA) showed that the CLNAs groups were arranged separately with a cumulative variance of 68.47 %.
CONCLUSIONS
The results show that PSO can be used as a source of CLAs but that it does not cause changes in body modulation and does not interfere in the antioxidant activity of healthy rats.
Topics: Adipose Tissue; Analysis of Variance; Animals; Chromatography, Gas; Dietary Supplements; Linoleic Acids, Conjugated; Linolenic Acids; Lythraceae; Male; Muscle, Skeletal; Plant Oils; Principal Component Analysis; Rats; Rats, Wistar
PubMed: 26922800
DOI: 10.1186/s12944-016-0214-7 -
Journal of Food Science and Technology Jan 2020Punicic acid (PA), a predominant fatty acid (85%) in pomegranate seeds, also called as an ω-5 fatty acid, is known to render various health beneficial effects to...
Punicic acid (PA), a predominant fatty acid (85%) in pomegranate seeds, also called as an ω-5 fatty acid, is known to render various health beneficial effects to humans. The objective of this study was to prepare and observe the effect of replacement of wheat flour with 5-12.5% punicic acid rich pomegranate seed powder (PSP, 9XXX fraction) on rheological, physico-sensory and antioxidant properties of bread. The increasing amount of PSP caused decrease in farinograph water absorption capacity, dough stability; amylograph peak viscosity; bread volume and overall quality score, whereas crumb hardness was increased. The combination of additives (CA) showed significant improvement in dough strength, texture and quality of bread with 10% PSP. The total polyphenol content (TPP) and radical scavenging activity (RSA) increased by 10- to 30-fold while PA was increased to 60-fold when compared to control. The recovery of PA from bread samples was in range of 45-60% and further increased by the addition of CA (65%). Hence, 10% PSP bread having 60% recovery of PA can be successfully considered for formulations without altering the rheological and sensory quality of bread. These results reveal that PA rich PSP prepared from a fruit industry by-product can be utilized for preparing antioxidant rich functional bread which also helps in overall improvement of bone health.
PubMed: 31975728
DOI: 10.1007/s13197-019-04055-3 -
Molecules (Basel, Switzerland) Sep 2022Over the last decades, we have witnessed an increasing interest in food-related products containing vegetable oils. These oils can be obtained either by extraction or by...
Over the last decades, we have witnessed an increasing interest in food-related products containing vegetable oils. These oils can be obtained either by extraction or by mechanical pressing of different parts of plants (e.g., seeds, fruit, and drupels). Producers of nutraceuticals have ceaselessly searched for unique and effective natural ingredients. The enormous success of argan oil has been followed by discoveries of other interesting vegetable oils (e.g., pomegranate oil) containing several bioactives. This work describes the pomegranate fruit extract and seed oil as a rich source of conjugated linolenic acid as a metabolite of punicic acid (PA), deriving from the omega-5 family (ω-5). Through the chemical characterization of PA, its nutritional and therapeutic properties are highlighted together with the physiological properties that encourage its use in human nutrition. We analyzed the composition of all fatty acids with beneficial properties occurring in pomegranate seed oil using gas chromatography (GC) with flame-ionization detection (FID) analysis combined with Fourier transform infrared spectroscopy (FTIR). Pomegranate seed oil mainly consists of 9,11,13-octadic-trienoic acid (18:3), corresponding to 73 wt % of the total fatty acids. Nine components were identified by GC in PSO, varying between 0.58 and 73.19 wt %. Using midinfrared (MIR) spectroscopy, we compared the composition of pomegranate seed oil with that of meadowfoam seed oil (MSO), which is also becoming increasingly popular in the food industry due to its high content of long chain fatty acids (C20-22), providing increased oil stability. From the results of FTIR and MIR spectroscopy, we found that punicic acid is unique in PSO (73.19 wt %) but not in MSO.
Topics: Chromatography, Gas; Fatty Acids; Humans; Linolenic Acids; Lythraceae; Plant Extracts; Plant Oils; Pomegranate; Seeds; Spectroscopy, Fourier Transform Infrared
PubMed: 36144599
DOI: 10.3390/molecules27185863 -
International Journal of Molecular... May 2023Punicic acid (PuA) is a polyunsaturated fatty acid with significant medical, biological, and nutraceutical properties. The primary source of punicic acid is the...
Punicic acid (PuA) is a polyunsaturated fatty acid with significant medical, biological, and nutraceutical properties. The primary source of punicic acid is the pomegranate seed oil obtained from fruits of trees that are mainly cultivated in subtropical and tropical climates. To establish sustainable production of PuA, various recombinant microorganisms and plants have been explored as platforms with limited efficiencies. In this study, the oleaginous yeast was employed as a host for PuA production. First, growth and lipid accumulation of were evaluated in medium supplemented with pomegranate seed oil, resulting in the accumulation of lipids up to 31.2%, consisting of 22% PuA esterified in the fraction of glycerolipids. In addition, lipid-engineered strains, transformed with the bifunctional fatty acid conjugase/desaturase from (PgFADX), showed the ability to accumulate PuA de novo. PuA was detected in both polar and neutral lipid fractions, especially in phosphatidylcholine and triacylglycerols. Promoter optimization for PgFADX expression resulted in improved accumulation of PuA from 0.9 to 1.8 mg/g of dry cell weight. The best-producing strain expressing PgFADX under the control of a strong erythritol-inducible promoter produced 36.6 mg/L PuA. These results demonstrate that the yeast is a promising host for PuA production.
Topics: Yarrowia; Fatty Acid Desaturases; Linolenic Acids; Plant Oils; Fatty Acids
PubMed: 37240172
DOI: 10.3390/ijms24108823 -
Carcinogenesis Oct 2014Prostate cancer (PCa) is the second cause of cancer deaths in men in the USA. When the cancer recurs, early stages can be controlled with hormone ablation therapy to...
Prostate cancer (PCa) is the second cause of cancer deaths in men in the USA. When the cancer recurs, early stages can be controlled with hormone ablation therapy to delay the rate of cancer progression but, over time, the cancer overcomes its hormone dependence, becomes highly aggressive and metastasizes. Clinical trials have shown that pomegranate juice (PJ) inhibits PCa progression. We have previously shown that the PJ components luteolin (L), ellagic acid (E) and punicic acid (P) together inhibit growth of hormone-dependent and -independent PCa cells and inhibit their migration and chemotaxis towards CXCL12, a chemokine that is important in PCa metastasis. On the basis of these findings, we hypothesized that L+E+P inhibit PCa metastasis in vivo. To test this possibility, we used a severe combined immunodeficiency mouse model in which luciferase-expressing human PCa cells were injected subcutaneously near the prostate. Tumor progression was monitored with bioluminescence imaging weekly. We found that L+E+P inhibits PC-3M-luc primary tumor growth, inhibits the CXCL12/CXCR4 axis for metastasis and none of the tumors metastasized. In addition, L+E+P significantly inhibits growth and metastasis of highly invasive Pten (-/-) ;K-ras (G12D) prostate tumors. Furthermore, L+E+P inhibits angiogenesis in vivo, prevents human endothelial cell (EC) tube formation in culture and disrupts preformed EC tubes, indicating inhibition of EC adhesion to each other. L+E+P also inhibits the angiogenic factors interleukin-8 and vascular endothelial growth factor as well as their induced signaling pathways in ECs. In conclusion, these results show that L+E+P inhibits PCa progression and metastasis.
Topics: Animals; Antineoplastic Agents, Phytogenic; Biological Products; Chemokine CXCL12; Ellagic Acid; Endothelium, Vascular; Humans; Linolenic Acids; Luteolin; Male; Mice; Mice, Inbred C57BL; Mice, SCID; Neovascularization, Pathologic; Prostatic Neoplasms; Proto-Oncogene Proteins c-akt; Receptors, CXCR4; Signal Transduction; Xenograft Model Antitumor Assays
PubMed: 25023990
DOI: 10.1093/carcin/bgu145 -
Nutrients Aug 2021Plant-derived conjugated linolenic acids (CLnA) have been widely studied for their preventive and therapeutic properties against diverse diseases such as cancer. In...
Plant-derived conjugated linolenic acids (CLnA) have been widely studied for their preventive and therapeutic properties against diverse diseases such as cancer. In particular, punicic acid (PunA), a conjugated linolenic acid isomer (C18:3 c9t11c13) present at up to 83% in pomegranate seed oil, has been shown to exert anti-cancer effects, although the mechanism behind its cytotoxicity remains unclear. Ferroptosis, a cell death triggered by an overwhelming accumulation of lipid peroxides, has recently arisen as a potential mechanism underlying CLnA cytotoxicity. In the present study, we show that PunA is highly cytotoxic to HCT-116 colorectal and FaDu hypopharyngeal carcinoma cells grown either in monolayers or as three-dimensional spheroids. Moreover, our data indicate that PunA triggers ferroptosis in carcinoma cells. It induces significant lipid peroxidation and its effects are prevented by the addition of ferroptosis inhibitors. A combination with docosahexaenoic acid (DHA), a known polyunsaturated fatty acid with anticancer properties, synergistically increases PunA cytotoxicity. Our findings highlight the potential of using PunA as a ferroptosis-sensitizing phytochemical for the prevention and treatment of cancer.
Topics: Antineoplastic Agents; Carcinoma; Cell Line, Tumor; Colorectal Neoplasms; Docosahexaenoic Acids; Ferroptosis; HCT116 Cells; Humans; Hypopharyngeal Neoplasms; Linolenic Acids; Lipid Peroxidation
PubMed: 34444911
DOI: 10.3390/nu13082751 -
PloS One Jul 2009Neutrophils play a major role in inflammation by releasing large amounts of ROS produced by NADPH-oxidase and myeloperoxidase (MPO). The proinflammatory cytokine...
BACKGROUND
Neutrophils play a major role in inflammation by releasing large amounts of ROS produced by NADPH-oxidase and myeloperoxidase (MPO). The proinflammatory cytokine TNFalpha primes ROS production through phosphorylation of the NADPH-oxidase subunit p47phox on Ser345. Conventional anti-inflammatory therapies remain partially successful and may have side effects. Therefore, regulation of neutrophil activation by natural dietary components represents an alternative therapeutic strategy in inflammatory diseases such as inflammatory bowel diseases. The aim of this study was to assess the effect of punicic acid, a conjugated linolenic fatty acid from pomegranate seed oil on TNFalpha-induced neutrophil hyperactivation in vitro and on colon inflammation in vivo.
METHODOLOGY AND PRINCIPAL FINDINGS
We analyzed the effect of punicic acid on TNFalpha-induced neutrophil upregulation of ROS production in vitro and on TNBS-induced rat colon inflammation. Results show that punicic acid inhibited TNFalpha-induced priming of ROS production in vitro while preserving formyl-methionyl-leucyl-phenylalanine (fMLP)-induced response. This effect was mediated by the inhibition of Ser345-p47phox phosphorylation and upstream kinase p38MAPK. Punicic acid also inhibited fMLP- and TNFalpha+fMLP-induced MPO extracellular release from neutrophils. In vivo experiments showed that punicic acid and pomegranate seed oil intake decreased neutrophil-activation and ROS/MPO-mediated tissue damage as measured by F2-isoprostane release and protected rats from TNBS-induced colon inflammation.
CONCLUSIONS/SIGNIFICANCE
These data show that punicic acid exerts a potent anti-inflammatory effect through inhibition of TNFalpha-induced priming of NADPH oxidase by targeting the p38MAPKinase/Ser345-p47phox-axis and MPO release. This natural dietary compound may provide a novel alternative therapeutic strategy in inflammatory diseases such as inflammatory bowel diseases.
Topics: Animals; Colitis; Linolenic Acids; Lymphocyte Activation; N-Formylmethionine Leucyl-Phenylalanine; NADPH Oxidases; Neutrophils; Phosphorylation; Rats; Reactive Oxygen Species; Tumor Necrosis Factor-alpha; p38 Mitogen-Activated Protein Kinases
PubMed: 19649246
DOI: 10.1371/journal.pone.0006458