Pinolenic acid

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.[Pubmed:38296168]

Fitoterapia. 2024 Jan 29;175:105842.

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.

Alternative sources of bioactive omega-3 fatty acids: what are the options?[Pubmed:38126230]

Curr Opin Clin Nutr Metab Care. 2024 Mar 1;27(2):106-115.

PURPOSE OF REVIEW: The very-long chain (VLC) omega-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) promote optimal development, physiological function and healthy ageing and help to manage disease. EPA and DHA are sourced mainly from fish, which is not sustainable. This review explores alternative sustainable sources. RECENT FINDINGS: Recent research confirms that higher intake and status of EPA and DHA are associated with health benefits including lower risk of incident type-2 diabetes and cardiovascular disease mortality. Meta-analyses confirm benefits of intravenous EPA and DHA in hospitalized adults. Algal oils and seed oils from some genetically modified (GM) plants are sources of EPA and DHA. An oil from GM camelina showed equivalence with fish oil in human trials. Ahiflower oil, a source of stearidonic acid, had biological effects in experimental studies that might translate into health benefits. An intravenous lipid emulsion based on Ahiflower oil has been tested in experimental research. Pine nut oil (PNO) is a source of Pinolenic acid, which is not an omega-3 PUFA but has similar actions. SUMMARY: Algal oils, oils from GM seed crops, Ahiflower oil and other sources of stearidonic acid, and nonomega-3 oils including PNO, are plant-sourced sustainable alternatives to fish-sourced VLC omega-3 PUFAs.

Structural and ligand binding analysis of the pet allergens Can f 1 and Fel d 7.[Pubmed:36960093]

Front Allergy. 2023 Mar 7;4:1133412.

INTRODUCTION: Pet lipocalins are respiratory allergens with a central hydrophobic ligand-binding cavity called a calyx. Molecules carried in the calyx by allergens are suggested to influence allergenicity, but little is known about the native ligands. METHODS: To provide more information on prospective ligands, we report crystal structures, NMR, molecular dynamics, and florescence studies of a dog lipocalin allergen Can f 1 and its closely related (and cross-reactive) cat allergen Fel d 7. RESULTS: Structural comparisons with reported lipocalins revealed that Can f 1 and Fel d 7 calyxes are open and positively charged while other dog lipocalin allergens are closed and negatively charged. We screened fatty acids as surrogate ligands, and found that Can f 1 and Fel d 7 bind multiple ligands with preferences for palmitic acid (16:0) among saturated fatty acids and oleic acid (18:1 cis-9) among unsaturated ones. NMR analysis of methyl probes reveals that conformational changes occur upon binding of Pinolenic acid inside the calyx. Molecular dynamics simulation shows that the carboxylic group of fatty acids shuttles between two positively charged amino acids inside the Can f 1 and Fel d 7 calyx. Consistent with simulations, the stoichiometry of oleic acid-binding is 2:1 (fatty acid: protein) for Can f 1 and Fel d 7. DISCUSSION: The results provide valuable insights into the determinants of selectivity and candidate ligands for pet lipocalin allergens Can f 1 and Fel d 7.

The Beneficial Effects of Pine Nuts and Its Major Fatty Acid, Pinolenic Acid, on Inflammation and Metabolic Perturbations in Inflammatory Disorders.[Pubmed:36674687]

Int J Mol Sci. 2023 Jan 6;24(2):1171.

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.

Fatty acid profiling in the genus Pinus in relation to its chemotaxonomy and nutritional or pharmaceutical properties.[Pubmed:36442579]

Phytochemistry. 2023 Feb;206:113517.

To develop and utilize the oil of Pinus seeds and explore natural resources rich in Pinolenic acid (PNLA), twenty-one Pinus taxa were evaluated in a search of Delta5-unsaturated polymethylene-interrupted fatty acids (Delta5-UPIFA)-rich oils. While the fatty acid (FA) composition was determined by GC-FID and GC-MS, NMR of crude oils proved to be a fast method for establishing the ratio between Delta5-UPIFA and total FA. For all analyzed taxa, both the geographical origin and the concentration of total FA in the seeds are provided. PNLA and sciadonic acids occurred in all samples, while taxoleic and bishomoPinolenic acids were present in most taxa. PNLA reached a maximum of 28.3% of total FA in P. mugo, and P. koraiensis showed the highest total FA amount (66.8 g/100 g seeds). The previously unanalyzed taxon P. ponderosa var. scopulorum can be considered a new PNLA source (17.1%). Principal Component Analysis showed that the similarities in FA profiles allow the grouping of the various taxa within Pinus subsections and confirmed the differential metabolic activities of Delta5 and Delta9 desaturase enzymes. This study showed that several underutilized Pinus taxa could be developed into renewable woody oil species, and their seeds could be used as raw materials for Delta5-UPIFA-rich oils extraction.

Pinolenic acid exhibits anti-inflammatory and anti-atherogenic effects in peripheral blood-derived monocytes from patients with rheumatoid arthritis.[Pubmed:35614190]

Sci Rep. 2022 May 25;12(1):8807.

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-alpha, IL-6, IL-1beta, 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-alpha by 23% (p = 0.048), IL-6 by 25% (p = 0.011), IL-1beta 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-alpha, 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.

Effects of Delayed-Release Olive Oil and Hydrolyzed Pine Nut Oil on Glucose Tolerance, Incretin Secretion and Appetite in Humans.[Pubmed:34684407]

Nutrients. 2021 Sep 27;13(10):3407.

BACKGROUND: To investigate the potential synergistic effects of olive oil releasing 2-oleoylglycerol and hydrolyzed pine nut oil containing 20% Pinolenic acid on GLP-1 secretion, glucose tolerance, insulin secretion and appetite in healthy individuals, when delivered to the small intestine as potential agonists of GPR119, FFA1 and FFA4. METHODS: Nine overweight/obese individuals completed three 6-h oral glucose tolerance tests (OGTTs) in a crossover design. At -30 min, participants consumed either: no oil, 6 g of hydrolyzed pine nut oil (PNO-FFA), or a combination of 3 g hydrolyzed pine nut oil and 3 g olive oil (PNO-OO) in delayed-release capsules. Repeated measures of glucose, insulin, C-peptide, GLP-1, GIP, ghrelin, subjective appetite and gastrointestinal tolerability were done. RESULTS: PNO-FFA augmented GLP-1 secretion from 0-360 min compared to no oil and PNO-OO (p < 0.01). GIP secretion was increased from 240-360 min after both PNO-FFA and PNO-OO versus no oil (p < 0.01). Both oil treatments suppressed subjective appetite by reducing hunger and prospective food consumption and increasing satiety (p < 0.05). CONCLUSIONS: In support of previous findings, 6 g of delayed-release hydrolyzed pine nut oil enhanced postprandial GLP-1 secretion and reduced appetite. However, no synergistic effect of combining hydrolyzed pine nut oil and olive oil on GLP-1 secretion was observed. These results need further evaluation in long-term studies including effects on bodyweight and insulin sensitivity.

Effect of pinolenic acid on oxidative stress injury in HepG2 cells induced by H(2)O(2).[Pubmed:34646537]

Food Sci Nutr. 2021 Aug 25;9(10):5689-5697.

To investigate the effect and mechanism of Pinolenic acid (PNA) on H(2)O(2)-induced oxidative stress injury in HepG2 cells. Methods: PNA was used to regulate oxidative stress injury of HepG2 cells induced by H(2)O(2). Quantification of cell survival rate, accumulation of intracellular reactive oxygen species (ROS), and expression levels of anti-oxidation-related genes were determined using MTT, fluorescent probe technology (DCFH-DA), and real-time quantitative reverse transcription polymerase chain technology (qRT-PCR) method, respectively. Meanwhile, the activity of intracellular antioxidant enzymes was determined by biochemical methods. The results showed that PNA improved the survival rate of HepG2 cells induced by H(2)O(2) (29.59%, high-dose group), reduced the accumulation of intracellular ROS (65.52%, high-dose group), and reduced the level of intracellular malondialdehyde (MDA; 65.52%, high-dose group). All these results were dose-dependent, which indicated that PNA can improve oxidative stress damage of cells. Furthermore, the mechanism of PNA regulating oxidative stress was investigated from the gene level. Results showed that under supplementation of PNA, the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) had been improved (39.74%, 17.58%, and 23.83%, high-dose group). Further studies on gene expression which controls the activity of antioxidant enzymes showed that under the regulation of PNA, the expression level of Keap1 gene was decreased, while Nrf2 gene was increased. The expression levels of HO-1 and NQO1 in the downstream of Nrf2 were increased. Results indicated that under the regulation of PNA, Nrf2 was separated from Keap1, entered the nucleus, bound to ARE, and up-regulated the expression levels of HO-1 and NQO1 genes. Conclusion: PNA has a conspicuous improvement effect on oxidative stress damage induced by H(2)O(2) in HepG2 cells. We also found the antioxidant mechanisms of PNA where it protected cells from oxidative stress damage by causing nuclear translocation of Nrf2 gene and up-regulated the expression levels of antioxidant enzymes in the downstream. This shows that PNA prevented oxidative stress by mediating the Keap1/Nrf2 transcriptional pathway and down-regulating enzyme activities.

Anti-inflammatory and immunoregulatory effects of pinolenic acid in rheumatoid arthritis.[Pubmed:34080609]

Rheumatology (Oxford). 2022 Mar 2;61(3):992-1004.

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-alpha 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-alpha 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-kappaB 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.

Fat regulatory mechanisms of pine nut oil based on protein interaction network analysis.[Pubmed:33852976]

Phytomedicine. 2021 Jun;86:153557.

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-gamma, 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-gamma, 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-gamma and SREBP-1c.

A review of the functional effects of pine nut oil, pinolenic acid and its derivative eicosatrienoic acid and their potential health benefits.[Pubmed:33831456]

Prog Lipid Res. 2021 Apr;82:101097.

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.

Acute effects of delayed-release hydrolyzed pine nut oil on glucose tolerance, incretins, ghrelin and appetite in healthy humans.[Pubmed:33059911]

Clin Nutr. 2021 Apr;40(4):2169-2179.

BACGROUND & AIM: Pinolenic acid, a major component (~20%) of pine nut oil, is a dual agonist of the free fatty acid receptors, FFA1 and FFA4, which may regulate release of incretins and ghrelin from the gut. Here, we investigated the acute effects of hydrolyzed pine nut oil (PNO-FFA), delivered to the small intestine by delayed-release capsules, on glucose tolerance, insulin, incretin and ghrelin secretion, and appetite. METHODS: In two cross-over studies, we evaluated 3 g unhydrolyzed pine nut oil (PNO-TG) or 3 g PNO-FFA versus no oil in eight healthy, non-obese subjects (study 1), and 3 g PNO-FFA or 6 g PNO-FFA versus no oil in ten healthy, overweight/obese subjects (study 2) in both studies given in delayed-release capsules 30 min prior to a 4-h-oral glucose tolerance test (OGTT). Outcomes were circulating levels of glucose, insulin, GLP-1, GIP, ghrelin, appetite and gastrointestinal tolerability during OGTT. RESULTS: Both 3 g PNO-FFA in study 1 and 6 g PNO-FFA in study 2 markedly increased GLP-1 levels (p < 0.001) and attenuated ghrelin levels (p < 0.001) during the last 2 h of the OGTT compared with no oil. In study 2, these effects of PNO-FFA were accompanied by an increased satiety and fullness (p < 0.03), and decreased prospective food consumption (p < 0.05). PNO-FFA caused only small reductions in glucose and insulin levels during the first 2 h of the OGTT. CONCLUSIONS: Our results provide evidence that PNO-FFA delivered to the small intestine by delayed-release capsules may reduce appetite by augmenting GLP-1 release and attenuating ghrelin secretion in the late postprandial state. CLINICAL TRIAL REGISTRY NUMBERS: NCT03062592 and NCT03305367.

Gamma-Linolenic and Pinolenic Acids Exert Anti-Inflammatory Effects in Cultured Human Endothelial Cells Through Their Elongation Products.[Pubmed:32898315]

Mol Nutr Food Res. 2020 Oct;64(20):e2000382.

SCOPE: Omega-3 fatty acids (FAs) from oily fish reduce cardiovascular disease. This may be partly due to modulation of endothelial cell (EC) inflammation. Fish stocks are declining and there is a need for sustainable alternative FAs. Gamma-linolenic acid (GLA) and Pinolenic acid (PLA) are plant-derived FAs, which can fulfil this role. METHODS AND RESULTS: EA.hy926 cells are exposed GLA and PLA prior to stimulation with tumor necrosis factor (TNF)-alpha. GLA and PLA are incorporated into ECs, resulting in increases in long-chain derivatives produced by elongase 5, dihomo-gamma-linolenic acid (DGLA), and eicosatrienoic acid (ETA). Both GLA and PLA (50 microm) decrease production of soluble intercellular adhesion molecule-1 (sICAM-1), monocyte chemoattractant protein 1 (MCP-1), and regulated on activation, normal T cell expressed and secreted (RANTES). However, decreases in these mediators are not seen after pre-treatment with GLA or PLA in elongase 5 silenced EA.hy926 cells. DGLA and ETA (10 microm) decrease EC production of sICAM-1, MCP-1, RANTES, and IL-6. All FAs reduce adhesion of THP-1 monocytes to EA.hy926 cells. Both PLA (50 microm) and ETA (10 microm) decrease NFkappaBp65 phosphorylation. CONCLUSION: These effects suggest potential for GLA, PLA and their long-chain derivatives, DGLA and ETA, as sustainable anti-inflammatory alternatives to fish-derived FAs.

Investigation of Modulatory Effect of Pinolenic Acid (PNA) on Inflammatory Responses in Human THP-1 Macrophage-Like Cell and Mouse Models.[Pubmed:31776889]

Inflammation. 2020 Apr;43(2):518-531.

Pinolenic acid (PNA) is a rare n-6 polyunsaturated fatty acid (n-6 PUFA) originally identified in pine seeds. Previous studies demonstrated that PNA and its elongation metabolite, Delta7-eicosatrienoic acid (Delta7-ETrA), exerted an anti-inflammatory effect in cultured cells by suppressing prostaglandin E(2) (PGE(2)) production. The objective of this study was to further examine the in vivo anti-inflammatory properties of PNA. Using human THP-1 macrophage, we first confirmed that incorporation of PNA into cellular phospholipids suppressed the production of interleukin-6 (IL-6) (by 46%), tumor necrosis factor-alpha (TNF-alpha) (by 18%), and prostaglandin E(2) (PGE(2)) (by 87%), and the expression of type-2 cyclooxygenase (COX-2) (by 27%). Furthermore, we demonstrated that injection of PNA or Delta7-ETrA suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema, as measured by ear thickness (by 15%) and biopsy weight (by up to 29%). Both PUFA also lowered proportions of infiltrated leukocytes, neutrophils, and macrophages using flow cytometric analysis. Topical application of PNA or Delta7-ETrA on mouse back skin suppressed TPA-induced pro-inflammatory mediator production, including IL-1beta, IL-6, TNF-alpha, and PGE(2), as well as the phosphorylation of p38- and JNK-mitogen-activated protein kinase (MAPK), but not that of ERK-MAPK. That no PNA or Delta7-ETrA was detected in the ear disc after the PUFA injection suggests that their anti-inflammatory effect might not be due to fatty acid incorporation, but to modulation of cell signaling. In conclusion, PNA and Delta7-ETrA exerted the in vivo anti-inflammatory effect by suppressing mouse ear edema and dorsal skin inflammation.

Pinolenic acid ameliorates oleic acid-induced lipogenesis and oxidative stress via AMPK/SIRT1 signaling pathway in HepG2 cells.[Pubmed:31430456]

Eur J Pharmacol. 2019 Oct 15;861:172618.

Pinolenic acid (PLA), a natural compound isolated from pine nut oil, has been reported to exert bioactivity against lipid anabolism. Nonetheless, the underlying mechanisms still poorly elucidated. The aim of this study is to comprehensively demonstrate the effects of PLA on oleic acid (OA)-induced non-alcoholic fatty liver disease (NAFLD) and their relationship with the lipid metabolic regulation. The results demonstrated that treatment with PLA dramatically inhibited lipid accumulation, oxidative stress as well as inflammatory responses induced by oleic acid in HepG2 cells. PLA also obviously decreased the levels of cellular triglyceride (TG), total cholesterol (TC), malondialdehyde (MDA), reactive oxygen species (ROS) and nitric oxide (NO). As well as PLA stilled promoted the antioxidant enzymes activity including superoxide dismutase (SOD) and glutathione peroxidase (GPX). Furthermore, PLA could increase the expressions of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase1 (HO-1) to alleviate oxidative damage. It also could reduce lipogenesis-related transcription factors expression, such as sterol regulatory element-binding protein 1 (SREBP1c), fatty acid synthase (FASN) and stearoyl-CoA desaturase 1 (SCD1). PLA treatment resulted in increasing phosphorylation of AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-alpha (PPARalpha) expression. However, pretreatment with compound C (inhibitor of AMPK) inhibited the effect of PLA on promoting the expression of p-AMPK, SIRT1 and PPARalpha for lipolysis. Taken together, these results demonstrated that PLA possessed the potential to prevent lipid accumulation in OA-induced HepG2 cells via upregulating the AMPK/SIRT1 signaling pathway, which supported the development of new drug candidate against non-alcoholic steatohepatitis.