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Molecules (Basel, Switzerland) Apr 2022Fatty acid synthase (FASN) is highly expressed in multiple types of human cancers and is recognized as one of the targets for treating cancer metastasis. α-Linolenic...
Fatty acid synthase (FASN) is highly expressed in multiple types of human cancers and is recognized as one of the targets for treating cancer metastasis. α-Linolenic acid is an omega-3 essential fatty acid and it possesses various biological activities. The present study was designed to reveal the effects of α-linolenic acid on osteosarcoma and to reveal whether the mechanism of α-linolenic acid in anticancer activity may be related to FASN inhibition. The cytotoxicity of α-linolenic acid was assessed in osteosarcoma MG63, 143B, and U2OS cells. Cell viability was detected by the MTT assay. The protein expression level was detected by western blotting. Flow cytometry, Annexin V/propidium iodide dual staining, and Hoechst 33258 staining were performed to assess the apoptotic effects. Wound healing assay was applied to detect the inhibitory effect of α-linolenic acid on osteosarcoma cells migration. The results showed that α-linolenic acid downregulated FASN expression. α-Linolenic acid inhibited osteosarcoma cell proliferation and migration in a dose-dependent manner. In addition, α-linolenic acid regulated endoplasmic reticulum transmembrane receptors and signal protein expression in osteosarcoma cells. The findings of the present study suggested that α-linolenic acid suppresses osteosarcoma cell proliferation and metastasis by inhibiting FASN expression, which provides a basis as a potential target for osteosarcoma treatment.
Topics: Apoptosis; Bone Neoplasms; Cell Line, Tumor; Cell Movement; Cell Proliferation; Fatty Acid Synthases; Humans; Osteosarcoma; alpha-Linolenic Acid
PubMed: 35566090
DOI: 10.3390/molecules27092741 -
Saudi Journal of Biological Sciences Nov 2019Non-alcoholic fatty liver disease (NAFLD) is a multi-factorial disease and the most common of chronic liver diseases worldwide. The four clinical-pathological entities... (Review)
Review
Non-alcoholic fatty liver disease (NAFLD) is a multi-factorial disease and the most common of chronic liver diseases worldwide. The four clinical-pathological entities which are usually followed by NAFLD course include non-alcoholic steatosis, non-alcoholic steatohepatitis, advanced fibrosis/cirrhosis, and hepatocellular carcinoma. The cornerstones of NAFLD management and treatment, however, are healthy lifestyles such as dietary modifications, regular physical activity, and gradual weight loss. At present, no drugs or pharmacological agents have been approved for long-term treatment of NAFLD. Therefore, lifestyle modification is considered the main clinical recommendation and an initial step for the management of NAFLD.
PubMed: 31762620
DOI: 10.1016/j.sjbs.2018.12.016 -
Molecular Biomedicine Feb 2021Alzheimer's disease (AD) is known by characteristic features, extracellular burden of amyloid-β and intracellular neuronal Tau. Microglia, the innate immune cell of...
Alzheimer's disease (AD) is known by characteristic features, extracellular burden of amyloid-β and intracellular neuronal Tau. Microglia, the innate immune cell of the brain has the ability to clear the burden of accumulated proteins via phagocytosis. But the excessive proinflammatory cytokine production, altered cellular signaling and actin remodeling hampers the process of migration and phagocytosis by microglia. Actin remodeling is necessary to initiate the chemotactic migration of microglia towards the target and engulf it. The formation of lamellipodia, filopodia, membrane ruffling and rapid turnover of F-actin is necessary to sense the extracellular target by the cells. Omega-3 fatty acids, are known to impose anti-inflammatory phenotype of microglia by enhancing its ability for migration and phagocytosis. But the role of omega-3 fatty acids in cellular actin remodeling, which is the basis of cellular functions such as migration and phagocytosis, is not well understood. Here, we have focused on the effect of dietary supplement of α-linolenic acid (ALA) on extracellular Tau internalization and assisted actin polymerization for the process. ALA is found to induce membrane ruffling and phagocytic cup formation along with cytoskeletal rearrangement. ALA also enhances the localization of Arp2/3 complex at the leading edge and its colocalization with F-actin to induce the actin polymerization. The excessive actin polymerization might help the cell to protrude forward and perform its migration. The results suggest that dietary supplement of ALA could play a neuroprotective role and slow down the AD pathology.
PubMed: 35006402
DOI: 10.1186/s43556-021-00028-1 -
Animals : An Open Access Journal From... Sep 2022We evaluated effects of dietary ground flaxseed on fecal and serum alpha-linolenic acid (ALA) concentrations, nutrient digestibility, and stool quality in female and...
We evaluated effects of dietary ground flaxseed on fecal and serum alpha-linolenic acid (ALA) concentrations, nutrient digestibility, and stool quality in female and male adult cats (n = 20 (8 males, 12 females); 3.95 ± 1.49 years of age (mean ± SD); 3.88 ± 0.82 kg BW). We hypothesized that adding ground flaxseed would increase serum ALA compared with feeding no flax, without changing nutrient digestibility. Cats were fed as-is 2.6% added-flaxseed (flax, n = 10) or no-flax (control, n = 10) diets (2.66 vs. 0.78% ALA of total fatty acids; crude protein 35%, fat 20%, fiber 3% as-fed) twice daily to maintain body weight for 28 days. Fecal collections were conducted on days 23−27 for total-tract nutrient digestibility, stool quality (scale 1−5; 1 = watery diarrhea, 5 = hard, dry, crumbly) and long-chain fatty acid (LCFA) analyses. Blood was collected on days 0, 14, and 28 for serum LCFA and chemistry analysis. Digestibility and fecal data were analyzed by ANOVA (SAS v9.4, Cary, NC, USA) and a repeated measures ANOVA for serum ALA. Flax-fed cats, compared with control-fed, had greater (p < 0.05) serum ALA after 14 days (4.00 vs. 0.71 µg/mL) and 28 days (7.83 and 3.67 µg/mL). No differences were observed in stool quality, and dry matter, protein, fat, and ALA digestibility. However, metabolizable energy was greater in the flax vs. control diet (4.18 vs. 3.91 kcal/g; p < 0.05). Overall, these data demonstrate that ground flaxseed added to cat diets increases serum ALA within 14 days, with no detriments to nutrient digestibility. We conclude that flaxseed can be used as a bioavailable source of ALA in cat diets.
PubMed: 36230284
DOI: 10.3390/ani12192543 -
The International Journal of Angiology... Sep 2019This review paper describes the effects of flaxseed and its components (flax oil, secoisolariciresinol diglucoside [SDG], flax lignan complex [FLC], and flaxseed protein... (Review)
Review
This review paper describes the effects of flaxseed and its components (flax oil, secoisolariciresinol diglucoside [SDG], flax lignan complex [FLC], and flaxseed protein hydrolysate [FPH]) on blood pressure (BP) in Sprague Dawley rats (SDR), spontaneously hypertensive rats (SHR), and humans. Flaxseed, flax oil, and FLC had variable effects on BP in humans, while SDG and FPH significantly reduced the BP in SDR and SHR. The effect of SDG was dose-dependent and long lasting. The lowering of BP is mediated through inhibition of soluble epoxide by -linolenic acid in flax oil, stimulation of guanylate cyclase and inhibition of angiotensin converting enzyme (ACE) by SDG, and inhibition of renin and ACE activity by FPH. Flaxseed, flax oil, and FLC have variable effects on BP (none, slight, and significant). They are effective in lowering BP in individuals with hypertension and metabolic syndrome but ineffective in healthy individuals' ineffectiveness of flaxseed and its compounds in lowering BP may be due to their low doses, long interval of dosing, short duration of consumption, and patient status. In conclusion, the data at present suggest that flaxseed, flax oil, and FLC cannot serve as therapeutic agents for the treatment of hypertension. However, they can be used as an adjunct in the treatment of hypertension. A clinical trial should be conducted of these agents with higher doses which would be given twice daily for long duration. Pure SDG and FPS may serve as therapeutic agents for the treatment of hypertension but they have not been tried in humans.
PubMed: 31452582
DOI: 10.1055/s-0039-1678691 -
Nutrients Mar 2023The effects of docosahexaenoic acid supplements on cognitive function have long been demonstrated, but the effects of alpha-linolenic acid, a precursor of... (Randomized Controlled Trial)
Randomized Controlled Trial
The effects of docosahexaenoic acid supplements on cognitive function have long been demonstrated, but the effects of alpha-linolenic acid, a precursor of docosahexaenoic acid, have not been fully tested. The search for functional foods that delay cognitive decline in the older adults is considered a very important area from a preventive perspective. The aim of this study was to conduct an exploratory evaluation of alpha-linolenic acid on various cognitive functions in healthy older subjects. Sixty healthy older adults aged 65 to 80 years, living in Miyagi prefecture, without cognitive impairment or depression, were included in the randomized, double-blinded, placebo-controlled clinical trial. Study subjects were randomly divided into two groups and received either 3.7 g/day of flaxseed oil containing 2.2 g of alpha-linolenic acid, or an isocaloric placebo (corn oil) containing 0.04 g of alpha-linolenic acid for 12 weeks. The primary endpoints were six cognitive functions closely related to everyday life: attention and concentration, executive function, perceptual reasoning, working memory, processing speed and memory function. After 12 weeks of intake, changes in verbal fluency scores on the frontal assessment battery at bedside, a neuropsychological test assessing executive function, in which participants are asked to answer as many words as possible in Japanese, were significantly greater in the intervention group (0.30 ± 0.53) than in the control group (0.03 ± 0.49, < 0.05). All other cognitive test scores were not significantly different between the groups. In conclusion, daily consumption of flaxseed oil containing 2.2 g alpha-linolenic acid improved cognitive function, specifically verbal fluency, despite the age-related decline, in healthy individuals with no cognitive abnormalities. Further validation studies focusing on the effects of alpha-linolenic acid on verbal fluency and executive function in older adults are needed, as verbal fluency is a predictor of Alzheimer's disease development, important for cognitive health.
Topics: Humans; Aged; Linseed Oil; alpha-Linolenic Acid; Docosahexaenoic Acids; Cognitive Dysfunction; Dietary Supplements; Double-Blind Method
PubMed: 36986229
DOI: 10.3390/nu15061499 -
International Journal of Molecular... Aug 2023The GC-MS profiling of the endogenous oxylipins (Me/TMS) from cucumber ( L.) leaves, flowers, and fruit peels revealed a remarkable abundance of...
The GC-MS profiling of the endogenous oxylipins (Me/TMS) from cucumber ( L.) leaves, flowers, and fruit peels revealed a remarkable abundance of 16-hydroxy-9,12,14-octadecatrienoic acid (16-HOT). Incubations of homogenates from these organs with α-linolenic acid yielded 16()-hydroperoxide (16-HPOT) as a predominant product. Targeted proteomic analyses of these tissues revealed the presence of several highly homologous isoforms of the putative "9-lipoxygenase type 6". One of these isoenzymes (CsLOX3, an 877 amino acid polypeptide) was prepared by heterologous expression in and exhibited 16()- and 13()-lipoxygenase activity toward α-linolenic and linoleic acids, respectively. Furthermore, α-linolenate was a preferred substrate. The molecular structures of 16()-HOT and 16()-HPOT (Me or Me/TMS) were unequivocally confirmed by the mass spectral data, H-NMR, 2D H-H-COSY, TOCSY, HMBC, and HSQC spectra, as well as enantiomeric HPLC analyses. Thus, the vegetative CsLOX3, biosynthesizing 16()-HPOT, is the first 16()-LOX and ω3-LOX ever discovered. Eicosapentaenoic and hexadecatrienoic acids were also specifically transformed to the corresponding ω3()-hydroperoxides by CsLOX3.
Topics: Cucumis sativus; alpha-Linolenic Acid; Escherichia coli; Proteomics; Fatty Acids, Omega-3; Hydrogen Peroxide; Lipoxygenases
PubMed: 37629162
DOI: 10.3390/ijms241612977 -
Nutrition & Metabolism Aug 2022Altered lipid profiles are frequently present in cancer, and it is necessary to elucidate the role of changed lipid profiles in hepatocellular carcinoma (HCC). We...
BACKGROUND
Altered lipid profiles are frequently present in cancer, and it is necessary to elucidate the role of changed lipid profiles in hepatocellular carcinoma (HCC). We conducted this study to investigate the changed lipid profile in HCC tissues and discover some remarkably changed lipid components, and to explore the function of changed lipid components in HCC development.
METHODS
Gas chromatography/mass spectrometer (GC/MS analysis) was employed to measure the abundance of fatty acids between HCC tissues and adjacent noncancerous tissues. The proliferative ability of HCC cells was determined by Cell Counting Kit-8 and EdU assays. Transwell and wound healing assays were employed to determine the migratory ability of HCC cells. Protein expression was assessed by western blot assay.
RESULTS
GC/MS analysis revealed that alpha-linolenic acid was present at lower levels in HCC tissues than that in the adjacent noncancerous tissues. Alpha-linolenic acid inhibited the proliferation, migration and invasion of HCC cells in vitro. Western blotting showed that alpha-linolenic acid treatment increased Farnesoid X receptor expression and decreased β-catenin and cyclinD1 expression.
CONCLUSIONS
Alpha-linolenic acid suppresses HCC progression through the FXR/Wnt/β-catenin signaling pathway. Rational use of alpha-linolenic acid may prevent the occurrence of liver cancer in the future.
PubMed: 35999582
DOI: 10.1186/s12986-022-00693-1 -
Perilla oil and α-linolenic acid ameliorated thrombosis in rats induced by collagen and epinephrine.Food Science and Biotechnology Jun 2023is an annual herbaceous plant widely cultivated for oil production in China, Japan, and Korea. In this study, we investigated the effect of perilla oil (PO) on...
is an annual herbaceous plant widely cultivated for oil production in China, Japan, and Korea. In this study, we investigated the effect of perilla oil (PO) on thrombosis induced by collagen and epinephrine (CE) in rats. The oral administration of PO significantly increased prothrombin time (PT) and activated partial thromboplastin time (aPTT) in the blood plasma and inhibited the expression of cells adhesion markers (CAMs) such as intercellular CAM-1 (ICAM-1), vascular CAM (VCAM-1), E-selectin and P-selectin in the aorta tissue. Furthermore, pulmonary occlusion induced by CE in rats was suppressed by PO. α-Linolenic acid (ALA) was quantified at 60.14 ± 2.50 g/100 g of PO, and its oral administration at the same concentration with that in PO exerted the similar effect on PT, aPTT, ICAM-1, VCAM-1, E-selectin and P-selectin in CE-induced thrombosis rats. Taken together, PO and ALA significantly ameliorated thrombosis by regulating CAMs.
PubMed: 37123064
DOI: 10.1007/s10068-022-01241-6 -
Nutrients Oct 2023We investigated the postpartum mental health of women who had consumed perilla oil or fish oil containing various omega-3 fatty acids for 12 weeks starting in... (Observational Study)
Observational Study Randomized Controlled Trial
Effects of Varied Omega-3 Fatty Acid Supplementation on Postpartum Mental Health and the Association between Prenatal Erythrocyte Omega-3 Fatty Acid Levels and Postpartum Mental Health.
We investigated the postpartum mental health of women who had consumed perilla oil or fish oil containing various omega-3 fatty acids for 12 weeks starting in mid-pregnancy. The association between fatty acids in maternal erythrocytes and mental health risk factors was also examined. Healthy Japanese primiparas in mid-pregnancy (gestational weeks 18-25) were randomly divided into two groups and consumed approximately 2.0 g/day of omega-3 fatty acids in either perilla oil (the ALA dose was 2.4 g/day) or fish oil (the EPA + DHA dose was 1.7 g/day) for 12 weeks. Maternal mental health was assessed using the Edinburgh Postnatal Depression Scale (EPDS) as the primary measure and the Mother-to-Infant Bonding Scale (MIBS) as the secondary measure. Data from an observational study were used as a historical control. Maternal blood, cord blood, and colostrum samples were collected for fatty acid composition analysis. In addition, completers of the observational studies were enrolled in a case-control study, wherein logistic regression analysis was performed to examine the association between maternal fatty acids and EPDS score. The proportion of participants with a high EPDS score (≥9) was significantly lower in the perilla oil group (12.0%, = 0.044) but not in the fish oil group (22.3%, = 0.882) compared with the historical control (21.6%), while the proportions between the former groups also tended to be lower ( = 0.059). No marked effect of omega-3 fatty acid intake was observed from the MIBS results. In the case-control study of the historical control, high levels of α-linolenic acid in maternal erythrocytes were associated with an EPDS score of <9 (odds ratio of 0.23, 95% confidence interval: 0.06, 0.84, = 0.018 for trend). The results of this study suggest that consumption of α-linolenic acid during pregnancy may stabilize postpartum mental health.
Topics: Female; Humans; Pregnancy; alpha-Linolenic Acid; Case-Control Studies; Dietary Supplements; Docosahexaenoic Acids; Eicosapentaenoic Acid; Erythrocytes; Fatty Acids; Fatty Acids, Omega-3; Fish Oils; Mental Health; Postpartum Period; Vitamins
PubMed: 37892462
DOI: 10.3390/nu15204388