Engineering Yarrowia lipolytica for Sustainable Production of the Pomegranate Seed Oil-Derived Punicic Acid.

Punicic acid is a conjugated linolenic acid with various biological activities including antiobesity, antioxidant, anticancer, and anti-inflammatory effects. It is often used as a nutraceutical, dietary additive, and animal feed. Currently, punicic acid is primarily extracted from pomegranate seed oil, but it is restricted due to the extended growth cycle, climatic limitations, and low recovery level. There have also been reports on the chemical synthesis of punicic acid, but it resulted in a mixture of structurally similar isomers, requiring additional purification/separation steps. In this study, a comprehensive strategy for the production of punicic acid in Yarrowia lipolytica was implemented by pushing the supply of linoleic acid precursors in a high-oleic oil strain, expressing multiple copies of the fatty acid conjugase gene from Punica granatum, engineering the acyl-editing pathway to improve the phosphatidylcholine pool, and promoting the assembly of punicic acid in the form of triglycerides. The optimal strain with high oil production capacity and a significantly increased punicic acid ratio accumulated 3072.72 mg/L punicic acid, accounting for 6.19% of total fatty acids in fed-batch fermentation, providing a viable, sustainable, and green approach for punicic acid production to substitute plant extraction and chemical synthesis production.

A new integrated strategy for high purity pinolenic acid production from Pinus koraiensis Sieb. et Zucc seed oil and evaluation of its hypolipidemic activity in vivo.

Pinolenic acid is a polyunsaturated fatty acid present only in Pinus koraiensis Sieb. et Zucc seed oil. In order to solve the structural instability problem of polyunsaturated fatty acids, pinolenic acid of P. koraiensis seed oil was effectively isolated and purified by the integrated strategy of ethyl esterification followed by urea inclusion for the first time. Under the optimal conditions after the Box-Benhnken Design experimental, ethyl pinolenate with high purity 94.95% could be obtained, and the average content of PNAEE can still reach 86.18%. Then ethyl pinolenate was characterized by Gas chromatography-mass spectrometry, Fourier transform infrared, and Nuclear magnetic resonance spectra, results showed that ethyl pinolenate was successfully prepared. In addition, the hypolipidemic activity of ethyl pinolenate had been tested in vivo and showed that ethyl pinolenate had obvious hypolipidemic activity. The new strategy for high purity ethyl pinolenate production from P. koraiensis seed oil possesses great potential in food healthy field in the future.

Effect of edible oil type on the formation of protein-bound Nε-(carboxymethyl)lysine in roasted pork patties.

Protein-bound Nε-(carboxymethyl)lysine (CML), an advanced glycation end product within meat products, poses a potential health risk to humans. The objective of this study was to explore the impact of various edible oils on the formation of protein-bound CML in roasted pork patties. Eleven commercially edible oils including lard oil, corn oil, palm oil, olive oil, flaxseed oil, blended oil, camellia oil, walnut oil, soybean oil, peanut oil, and colza oil were added to pork tenderloin mince, respectively, at a proportion of 4 % to prepare raw pork patties. The protein-bound CML contents in the pork patties were determined by HPLC-MS/MS before and after roasting at 200 °C for 20 min. The results indicated that walnut oil, flaxseed oil, colza oil, olive oil, lard oil, corn oil, blended oil, and palm oil significantly reduced the accumulation of protein-bound CML in pork patties, of which the inhibition rate was in the 24.43 %-37.96 % range. Moreover, the addition of edible oil contributed to a marginal reduction in the loss of lysine. Meanwhile, glyoxal contents in pork patties were reduced by 16.72 %-43.21 % after roasting. Other than blend oil, all the other edible oils restrained protein oxidation in pork patties to varying degrees (between 20.16 % and 61.26 %). In addition, camellia oil, walnut oil, and flaxseed oil increased TBARS values of pork patties by 2.2-8.6 times when compared to the CON group. After analyzing the fatty acid compositions of eleven edible oils, five main fatty acids (palmitic acid, stearic acid, oleic acid, linoleic acid, and linolenic acid) were selected to establish Myofibrillar protein-Glucose-fatty acids systems to simulate the roasting process. The results showed that palmitic acid, oleic acid, linoleic acid, and linolenic acid obviously mitigated the formation of myofibrillar protein-bound CML, exhibiting suppression rates ranging from 10.38 % to 40.32 %. In conclusion, the addition of specific edible oil may curb protein-bound CML production in roasted pork patty by restraining protein or lipid oxidation, reducing lysine loss, and suppressing glyoxal production, which may be attributed to the fatty acid compositions of edible oils. This finding provides valuable guidance for the selection of healthy roasting oils in the thermal processing of meat products.

Study on the thermal oxidation of oleic, linoleic and linolenic acids by synchrotron radiation photoionization mass spectrometry.

RATIONALE: Cooking oil fumes contain numerous hazardous and carcinogenic chemicals, posing potential threats to human health. However, the sources of these species remain ambiguous, impeding health risk assessment, pollution control and mechanism research. METHODS: To address this issue, the thermal oxidation of three common unsaturated fatty acids (UFAs), namely oleic, linoleic and linolenic acids, present in vegetable oils was investigated. The volatile and semi-volatile products were comprehensively characterized by online synchrotron radiation photoionization mass spectrometry (SR-PIMS) with two modes, which were validated and complemented using offline gas chromatography (GC)/MS methods. Tunable SR-PIMS combined with photoionization efficiency curve simulation enabled the recognition of isomers/isobars in gaseous fumes. RESULTS: SR-PIMS revealed over 100 products, including aldehydes, alkenes, furans, aromatic hydrocarbons, etc., such as small molecules of formaldehyde, acetaldehyde, acrolein, ethylene and furan, which are not readily detected by conventional GC/MS; and some unreported fractions, e.g. ketene, 4-ethylcyclohexene and cycloundecene(E), were also observed. Furthermore, real-time monitoring of product emissions during the thermal oxidation of the three UFAs via SR-PIMS revealed that linolenic acid may be the major source of acrolein. CONCLUSION: SR-PIMS has been demonstrated as a powerful technique for online investigation of cooking oil fumes. This study achieved comprehensive characterization of volatile and semi-volatile products from the thermal oxidation of oleic, linoleic and linolenic acids, facilitating the traceability of species in cooking fumes and aiding in exploring the thermal reactions of different vegetable oils.

The Beneficial Effects of Pine Nuts and Its Major Fatty Acid, Pinolenic Acid, on Inflammation and Metabolic Perturbations in Inflammatory Disorders.

Inflammatory disorders such as atherosclerosis, diabetes and rheumatoid arthritis are regulated by cytokines and other inflammatory mediators. Current treatments for these conditions are associated with significant side effects and do not completely suppress inflammation. The benefits of diet, especially the role of specific components, are poorly understood. Polyunsaturated fatty acids (PUFAs) have several beneficial health effects. The majority of studies on PUFAs have been on omega-3 fatty acids. This review will focus on a less studied fatty acid, pinolenic acid (PNLA) from pine nuts, which typically constitutes up to 20% of its total fatty acids. PNLA is emerging as a dietary PUFA and a promising supplement in the prevention of inflammatory disorders or as an alternative therapy. Some studies have shown the health implications of pine nuts oil (PNO) and PNLA in weight reduction, lipid-lowering and anti-diabetic actions as well as in suppression of cell invasiveness and motility in cancer. However, few reviews have specifically focused on the biological and anti-inflammatory effects of PNLA. Furthermore, in recent bioinformatic studies on human samples, the expression of many mRNAs and microRNAs was regulated by PNLA indicating potential transcriptional and post-transcriptional regulation of inflammatory and metabolic processes. The aim of this review is to summarize, highlight, and evaluate research findings on PNO and PNLA in relation to potential anti-inflammatory benefits and beneficial metabolic changes. In this context, the focus of the review is on the potential actions of PNLA on inflammation along with modulation of lipid metabolism and oxidative stress based on data from both in vitro and in vivo experiments, and human findings, including gene expression analysis.

Pomegranate Seed Oil as a Source of Conjugated Linolenic Acid (CLnA) Has No Effect on Atherosclerosis Development but Improves Lipid Profile and Affects the Expression of Lipid Metabolism Genes in apoE/LDLR-/- Mice.

The aim of this study was to evaluate the anti-atherosclerotic effect of pomegranate seed oil as a source of conjugated linolenic acid (CLnA) (cis-9,trans-11,cis-13; punicic acid) compared to linolenic acid (LnA) and conjugated linoleic acid (CLA) (cis-9,trans-11) in apoE/LDLR-/- mice. In the LONG experiment, 10-week old mice were fed for the 18 weeks. In the SHORT experiment, 18-week old mice were fed for the 10 weeks. Diets were supplied with seed oils equivalent to an amount of 0.5% of studied fatty acids. In the SHORT experiment, plasma TCh and LDL+VLDL cholesterol levels were significantly decreased in animals fed CLnA and CLA compared to the Control. The expression of PPARα in liver was four-fold increased in CLnA group in the SHORT experiment, and as a consequence the expression of its target gene ACO was three-fold increased, whereas the liver's expression of SREBP-1 and FAS were decreased in CLnA mice only in the LONG experiment. Punicic acid and CLA isomers were determined in the adipose tissue and liver in animals receiving pomegranate seed oil. In both experiments, there were no effects on the area of atherosclerotic plaque in aortic roots. However, in the SHORT experiment, the area of atherosclerosis in the entire aorta in the CLA group compared to CLnA and LnA was significantly decreased. In conclusion, CLnA improved the lipid profile and affected the lipid metabolism gene expression, but did not have the impact on the development of atherosclerotic plaque in apoE/LDLR-/- mice.

Systematical Ingredient Investigations of Ficus tikoua Bur. Fruit and Immunoregulatory and Antioxidant Effects of Different Fractions.

Although the fruit of Ficus tikoua Bur. has been consumed by montanic people in China for centuries, its chemical and biological composition was still unclear. A series of comprehensive investigations on its chemical constituents and bioactivities were carried out for the first time. As a result, six compounds were isolated and identified as the main components in this fruit. GC-MS analysis of the lipid components demonstrated that Ficus tikoua Bur. fruit contains some wholesome constituents such as fatty acids, vitamins, triterpenoids, and phytosterols. The fatty acids are mainly composed of linolenic acid (61.27%) and linoleic acid (22.79%). Furthermore, this fruit contains a relative high content of crude protein (9.41 ± 0.03%), total amino acids (9.28%), and total polyphenols (0.86 ± 0.01 g/100 g). The analysis of monosaccharide composition showed that the total polysaccharide mainly consists of glucose, glucuronic acid, xylose, arabinose, mannose, galactose, galacturonic acid, and rhamnose. The polysaccharide, polyphenol, water, ethanol, and flavonoid extracts exhibited prominent antioxidant activity determined by ABTS, DPPH, and FRAPS methods. Meanwhile, the total polysaccharide exhibited significant immunomodulatory effect by enhancing the release of cytokines and expression of iNOS and COX-2 in RAW264.7 cells, significantly decreasing the expression of c-Jun and p65 proteins in the cytoplasm; increasing the translocation of c-Jun and p65 to the nucleus; and regulating the phosphorylation level of Akt, PI3K, and PDK1 in the PI3K/AKT signaling pathway. This study proved that the fruit of F. tikoua is a reliable source of functional food.

Changes in Chemical Composition of Flaxseed Oil during Thermal-Induced Oxidation and Resultant Effect on DSC Thermal Properties.

To investigate the changes in chemical composition of flaxseed oil during thermal-induced oxidation and the resultant effect on thermal properties, samples with different oxidation levels were obtained by being heated at 180 °C for two hours and four hours. The oxidation degree was evaluated using peroxide value (PV), extinction coefficient at 232 nm and 268 nm (K232 and K268), and total polar compounds (TPC). Using chromatography, the fatty acid profile and triacylglycerol (TAG) profile were examined. Differential scanning calorimetry (DSC) was used to determine the crystallization and melting profiles. Thermal-induced oxidation of flaxseed oil led to a significant increase (p < 0.05) in PV, K232, K268, and TPC, but the relative content of linolenic acid (Ln) and LnLnLn reduced dramatically (p < 0.05). TPC derived from lipid degradation affected both crystallization and melting profiles. Statistical correlations showed that the onset temperature (Ton) of the crystallization curve was highly correlated with K232, TPC, and the relative content of LnLnLn (p < 0.05), whereas the offset temperature (Toff) of the melting curve was highly correlated with the relative content of most fatty acids (p < 0.05). This finding provides a new way of rapid evaluation of oxidation level and changes of chemical composition for flaxseed oils using DSC.

Cold-Pressed Pomegranate Seed Oil: Study of Punicic Acid Properties by Coupling of GC/FID and FTIR.

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.

Linoleic and linolenic acids reduce the effects of heat stress-induced damage in pig oocytes during maturation in vitro.

Elevated environmental temperatures can induce heat stress which could reduce fertility and early embryonic development. Fatty acids can initiate an endergonic reaction that absorbs cellular heat and decreases intracellular temperature. This study's objective was to minimize heat stress-induced damage to in vitro matured oocytes by supplementing maturation media with either 50 µM linoleic or linolenic acid or both (25 or 50 µM) during maturation at either 38.5 or 41.5°C. Oocytes were evaluated for intracellular antioxidative pathways, fertilization characteristics, or early embryonic development. Elevated maturation temperatures increased (p < 0.05) reactive oxygen species (ROS) formation and supplementation with linoleic or linolenic acid decreased (p < 0.05) ROS in oocytes matured at 41.5°C. Maturation temperature had an effect (p < 0.05) on the intracellular antioxidative pathways of the oocyte except for glutathione peroxidase activity. Regardless of maturation temperature, supplementation with linoleic or linolenic acid increased (p < 0.05) the enzyme activities and glutathione concentrations in the oocytes compared to no fatty acid supplementation. Supplementation of both linoleic and linolenic acid decreased (p < 0.05) polyspermic fertilization rates. Supplementing either 25 or 50 µM linoleic and linolenic acid to maturing oocytes at 41.5°C increased (p < 0.05) cleavage rates by 48 h after IVF and the blastocyst formation rates by 144 h after IVF compared to other treatments. Oocytes matured at 38.5°C had greater (p < 0.05) embryonic development than those matured at 41.5°C except for those supplemented with 50 µM linoleic and linolenic acid. Supplementing 50 µM linoleic and linolenic acid to the maturation medium of pig oocytes reduces the effects of heat stress-induced damage.

Pinolenic acid exhibits anti-inflammatory and anti-atherogenic effects in peripheral blood-derived monocytes from patients with rheumatoid arthritis.

Pinolenic acid (PNLA), an omega-6 polyunsaturated fatty acid from pine nuts, has anti-inflammatory and anti-atherogenic effects. We aimed to investigate the direct anti-inflammatory effect and anti-atherogenic effects of PNLA on activated purified CD14 monocytes from peripheral blood of patients with rheumatoid arthritis (RA) in vitro. Flow cytometry was used to assess the proportions of CD14 monocytes expressing TNF-α, IL-6, IL-1ß, and IL-8 in purified monocytes from patients with RA after lipopolysaccharide (LPS) stimulation with/without PNLA pre-treatment. The whole genomic transcriptome (WGT) profile of PNLA-treated, and LPS-activated monocytes from patients with active RA was investigated by RNA-sequencing. PNLA reduced percentage of monocytes expressing cytokines: TNF-α by 23% (p = 0.048), IL-6 by 25% (p = 0.011), IL-1ß by 23% (p = 0.050), IL-8 by 20% (p = 0.066). Pathway analysis identified upstream activation of peroxisome proliferator-activated receptors (PPARs), sirtuin3, and let7 miRNA, and KLF15, which are anti-inflammatory and antioxidative. In contrast, DAP3, LIF and STAT3, which are involved in TNF-α, and IL-6 signal transduction, were inhibited. Canonical Pathway analysis showed that PNLA inhibited oxidative phosphorylation (p = 9.14E-09) and mitochondrial dysfunction (p = 4.18E-08), while the sirtuin (SIRTs) signalling pathway was activated (p = 8.89E-06) which interfere with the pathophysiological process of atherosclerosis. Many miRNAs were modulated by PNLA suggesting potential post-transcriptional regulation of metabolic and immune response that has not been described previously. Multiple miRNAs target pyruvate dehydrogenase kinase-4 (PDK4), single-immunoglobulin interleukin-1 receptor molecule (SIGIRR), mitochondrially encoded ATP synthase membrane subunit 6 (MT-ATP6) and acetyl-CoA acyltranferase2 (ACAA2); genes implicated in regulation of lipid and cell metabolism, inflammation, and mitochondrial dysfunction. PNLA has potential anti-atherogenic and immune-metabolic effects on monocytes that are pathogenic in RA and atherosclerosis. Dietary PNLA supplementation regulates key miRNAs that are involved in metabolic, mitochondrial, and inflammatory pathways.

Anti-inflammatory and immunoregulatory effects of pinolenic acid in rheumatoid arthritis.

OBJECTIVES: In pre-clinical studies, pinolenic acid (PNLA), an omega-6-polyunsaturated fatty acid from pine nuts, has shown anti-inflammatory effects. We aimed to investigate the effect of PNLA in human cell lines and peripheral blood mononuclear cells (PBMCs) from RA patients and healthy controls (HCs). METHODS: A modified Boyden chamber was used to assess chemokine-induced migration of THP-1 monocytes. Macropinocytosis was assessed using Lucifer yellow and oxidized low-density lipoprotein (oxLDL) uptake using DiI-labelled oxLDL in THP-1 macrophages and human monocyte-derived macrophages (HMDMs). IL-6, TNF-α and prostaglandin E2 (PGE2) release by lipopolysaccharide (LPS)-stimulated PBMCs from RA patients and HCs was measured by ELISA. The transcriptomic profile of PNLA-treated, LPS-activated PBMCs was investigated by RNA-sequencing. RESULTS: PNLA reduced THP-1 cell migration by 55% (P < 0.001). Macropinocytosis and DiI-oxLDL uptake were reduced by 50% (P < 0.001) and 40% (P < 0.01), respectively, in THP-1 macrophages and 40% (P < 0.01) and 25% (P < 0.05), respectively, in HMDMs. PNLA reduced IL-6 and TNF-α release from LPS-stimulated PBMCs from RA patients by 60% (P < 0.001) and from HCs by 50% and 35%, respectively (P < 0.01). PNLA also reduced PGE2 levels in such PBMCs from RA patients and HCs (P < 0.0001). Differentially expressed genes whose expression was upregulated included pyruvate dehydrogenase kinase-4, plasminogen activator inhibitor-1, fructose bisphosphatase1 and N-Myc downstream-regulated gene-2, which have potential roles in regulating immune and metabolic pathways. Pathway analysis predicted upstream activation of the nuclear receptors peroxisome proliferator-activated receptors involved in anti-inflammatory processes, and inhibition of nuclear factor-κB and signal transducer and activator of transcription 1. CONCLUSIONS: PNLA has immune-metabolic effects on monocytes and PBMCs that are pathogenic in RA and atherosclerosis. Dietary PNLA supplementation may be beneficial in RA.

Direct effects of linoleic and linolenic acids on bovine uterine function using in vivo and in vitro studies.

The aim of the present study was to evaluate the effects of continuous administration of linoleic acid or linolenic acid into the intra-uterine horn, ipsilateral to the corpus luteum, on the duration of the estrous cycle and plasma progesterone (P4) concentration. The effects of linoleic and linolenic acids on bovine uterine and luteal functions were also studied using a tissue culture system. Intra-uterine administration of linoleic or linolenic acid (5 mg/10 ml of each per day) in cows, between days 12 and 21, resulted in a prolonged estrous cycle compared to the average duration of the last one to three estrous cycles before administration in each group (P < 0.05). Moreover, plasma P4 concentration in cows treated with linoleic or linolenic acid was high between days 19 and 21 (linoleic acid), or on day 20 (linolenic acid), compared to that of the control cows (saline administration; P < 0.05 or lower). Both linoleic (500 µg/ml) and linolenic (5 and 500 µg/ml) acids stimulated prostaglandin (PG) E2 but inhibited PGF2α production by cultured endometrial tissue (P < 0.01), while P4 production by cultured luteal tissue was not affected. These findings suggest that both linoleic and linolenic acids support luteal P4 production by regulating endometrial PG production and, subsequently, prolonging the duration of the estrous cycle in cows.

Punicic Acid Triggers Ferroptotic Cell Death in Carcinoma Cells.

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.

Ferroptotic cell death triggered by conjugated linolenic acids is mediated by ACSL1.

Ferroptosis is associated with lipid hydroperoxides generated by the oxidation of polyunsaturated acyl chains. Lipid hydroperoxides are reduced by glutathione peroxidase 4 (GPX4) and GPX4 inhibitors induce ferroptosis. However, the therapeutic potential of triggering ferroptosis in cancer cells with polyunsaturated fatty acids is unknown. Here, we identify conjugated linoleates including α-eleostearic acid (αESA) as ferroptosis inducers. αESA does not alter GPX4 activity but is incorporated into cellular lipids and promotes lipid peroxidation and cell death in diverse cancer cell types. αESA-triggered death is mediated by acyl-CoA synthetase long-chain isoform 1, which promotes αESA incorporation into neutral lipids including triacylglycerols. Interfering with triacylglycerol biosynthesis suppresses ferroptosis triggered by αESA but not by GPX4 inhibition. Oral administration of tung oil, naturally rich in αESA, to mice limits tumor growth and metastasis with transcriptional changes consistent with ferroptosis. Overall, these findings illuminate a potential approach to ferroptosis, complementary to GPX4 inhibition.

Beneficial Impacts of Alpha-Eleostearic Acid from Wild Bitter Melon and Curcumin on Promotion of CDGSH Iron-Sulfur Domain 2: Therapeutic Roles in CNS Injuries and Diseases.

Neuroinflammation and abnormal mitochondrial function are related to the cause of aging, neurodegeneration, and neurotrauma. The activation of nuclear factor κB (NF-κB), exaggerating these two pathologies, underlies the pathogenesis for the aforementioned injuries and diseases in the central nervous system (CNS). CDGSH iron-sulfur domain 2 (CISD2) belongs to the human NEET protein family with the [2Fe-2S] cluster. CISD2 has been verified as an NFκB antagonist through the association with peroxisome proliferator-activated receptor-ß (PPAR-ß). This protective protein can be attenuated under circumstances of CNS injuries and diseases, thereby causing NFκB activation and exaggerating NFκB-provoked neuroinflammation and abnormal mitochondrial function. Consequently, CISD2-elevating plans of action provide pathways in the management of various disease categories. Various bioactive molecules derived from plants exert protective anti-oxidative and anti-inflammatory effects and serve as natural antioxidants, such as conjugated fatty acids and phenolic compounds. Herein, we have summarized pharmacological characters of the two phytochemicals, namely, alpha-eleostearic acid (α-ESA), an isomer of conjugated linolenic acids derived from wild bitter melon (Momordica charantia L. var. abbreviata Ser.), and curcumin, a polyphenol derived from rhizomes of Curcuma longa L. In this review, the unique function of the CISD2-elevating effect of α-ESA and curcumin are particularly emphasized, and these natural compounds are expected to serve as a potential therapeutic target for CNS injuries and diseases.

A review of the functional effects of pine nut oil, pinolenic acid and its derivative eicosatrienoic acid and their potential health benefits.

Pine nut oil (PNO) is rich in a variety of unusual delta-5-non-methylene-interrupted fatty acids (NMIFAs), including pinolenic acid (PLA; all cis-5,-9,-12 18:3) which typically comprises 14 to 19% of total fatty acids. PLA has been shown to be metabolised to eicosatrienoic acid (ETA; all cis-7,-11,-14 20:3) in various cells and tissues. Here we review the literature on PNO, PLA and its metabolite ETA in the context of human health applications. PNO and PLA have a range of favourable effects on body weight as well as fat deposition through increased energy expenditure (fatty acid oxidation) and decreased food energy intake (reduced appetite). PNO and PLA improve blood and hepatic lipids in animal models and insulin sensitivity in vitro and reduce inflammation and modulate immune function in vitro and in animal models. The few studies which have examined effects of ETA indicate it has anti-inflammatory properties. Another NMIFA from PNO, sciadonic acid (all cis-5,-11,-14 20:3), has generally similar properties to PLA where these have been investigated. There is potential for human health benefits from PNO, its constituent NMIFA PLA and the PLA derivative ETA. However further studies are needed to explore the effects in humans.

Fat regulatory mechanisms of pine nut oil based on protein interaction network analysis.

BACKGROUND: Pine nut oil (PNO), a standardized and well-defined extract of Pinus koraiensis (Korean pine), has beneficial effects on wound healing, inflammatory diseases, and cancer. However, the explanation for the mechanism by which PNO reduces body fat remains uncertain. We performed a protein-protein interaction network (PPIN) analysis to explore the genes associated with pinolenic acid using the MEDILINE database from PubChem and PubMed. It was concluded through the PPIN analysis that PNO was involved in a neutral lipid biosynthetic process. PURPOSE: This study evaluated the effects of PNO predicted by the network analysis of fat accumulation in chronic obesity mouse models established by feeding a high fat diet (HFD) to C57BL/6J mice and explored potential mechanisms. METHODS: HFD mice were fed only HFD or HFD with PNO at 822 and 1644 mg/kg. After an oral administration of 7 weeks, several body weight and body fat-related parameters were examined, including the following: adipose weight, adipocyte size, serum lipid profiles, adipocyte expression of PPAR-γ, sterol regulatory element binding protein (SREBP)-1c, lipoprotein lipase (LPL) and leptin. RESULTS: We showed that oral administration of PNO to HFD mice reduces body fat weight, fat in tissue, white adipose tissue weight, and adipocyte size. The serum cholesterol was improved in the HFD mice treated with PNO. Additionally, PNO has significantly attenuated the HFD-induced changes in the adipose tissue expression of PPAR-γ, SREBP-1c, LPL, and leptin. CONCLUSIONS: The findings from this study based on the PPIN analysis suggest that PNO has potential as drug to reduce body fat through fat regulatory mechanisms by PPAR-γ and SREBP-1c.

Physicochemical characterization of oil, antioxidant potential, and phenolic profile of seeds isolated from Tunisian pomegranate (Punica granatum L.) cultivars.

Pomegranate (Punica granatum L.) seeds oils (PSO) from three Tunisian varieties namely Jebali, Testouri, and Gabsi were extracted by ultrasonic-assisted extraction and analyzed for their physicochemical properties, fatty acids (FA) profile, and sterol composition. PSO of Gabsi and Testouri showed the best quality indexes in terms of peroxide and acid values and the highest oxidative stability index was observed for PSO of Gabsi ecotype (2.534 hr). Polyphenol content of PSO of Gabsi ecotype (886.909 mg/kg) was roughly 3 and 23 times higher than that of Jebali and Testouri ecotypes, respectively. Twelve FAs were identified by GC/FID. Punicic acid was the major compounds ranged from 81.53% (Testouri) to 86.41% (Gabsi). The unsaturated/saturated FA ratios of PSO were 14.53, 15.95, and 18.68, respectively for Gabsi, Testouri, and Jebali, respectively. Phytosterols were also identified and ß-sitosterol was the major compound in PSO. In addition, the phytochemical and antioxidant properties of phenolic extracts obtained from pomegranate seeds residues were investigated. Pomegranate seeds extract (PSE) of Gabsi cultivar showed the highest content of polyphenols (64.762 mg CAE/g) and flavonoids (7.127 mg RE/g). Antioxidant potential of extracts was performed using DPPH test and total antioxidant capacity (TAC). Results revealed that Gabsi cultivar was the most reactive extract with EC50 of 0.105 mg/mL for DPPH test and 40.622 mg AA/g for TAC. Phenolic profiles of PSE were also investigated. Results showed the importance of cultivar selection in the potential use of bioactive compounds of seeds as nutraceutical ingredients in food and chemical industries. PRACTICAL APPLICATION: Three Tunisian pomegranate cultivars namely Jebali, Testouri, and Gabsi were investigated for their seeds oil and phenolic composition. Pomegranate seeds oil (PSO) are rich in bioactive polyunsaturated fatty acids and phytosterols that can be of interest in several food and chemical industrial applications. Moreover, pomegranate seeds extracts are a natural source of antioxidant components, such as phenolic compounds, that can be used by the pharmaceutical industry as promising nutraceutical ingredients. The obtained results can be used to provide guidance on cultivar selection during industrial applications.

Antioxidant and antitumoral activities of isolated macamide and macaene fractions from Lepidium meyenii (Maca).

In this paper, a UPLC-ESI-MS was established to analyze macamide and macaene fractions from Lepidium meyenii (Maca). The antioxidant activity of Maca crude extract (MCE), total macamides (TMM) and total macaenes (TME) was evaluated by DPPH radical scavenging, ABTS radical scavenging and reducing power. The ability of MCE, TMM and TME against multiple cancer cell lines (leukemia HL-60, lung cancer A549, liver cancer SMMC-7721, breast cancer MCF-7, and colon cancer SW480) was used to evaluate their anticancer activity. The results demonstrate that TMM has the best free radical scavenging ability and reducing power compared to MCE, TME, and TMM, TME has the weakest antioxidant capacity compared to them. The difference in antioxidant properties between TMM and TME may be caused by benzylated alkamide in the chemical structure. TMM also has a good inhibitory effect on the five cancer cells. N-benzyl-(9Z, 12Z, 15Z)-octadecatrienamide (NBot) is the most cytotoxicity inhibitory of the macamides tested. The inhibitory effect of N-benzyl-9Z, 12Z-octadecadienamide (NBod) on colon cancer SW480 is near that of control group, while the inhibitory rates of NBot on leukemia HL-60, lung cancer A549, liver cancer SMMC-7721, and breast cancer MCF-7 are near those of the control group. Hence, NBot can be considered to have great potential as a natural drug with high efficiency and low side effects for cancer therapy.