PMID: 

Front Microbiol. 2019 ;10:867. Epub 2019 Apr 24. PMID: 31105665

Abstract Title: 

Effect of Quercetin Rich Onion Extracts on Bacterial Quorum Sensing.

Abstract: 

Quorum sensing (QS) regulates bacterial gene expression and studies suggest quercetin, a flavonol found in onion, as a QS inhibitor. There are no studies showing the anti-QS activity of plants containing quercetin in its native glycosylated forms. This study aimed to evaluate the antimicrobial and anti-QS potential of organic extracts of onion varieties and its representative phenolic compounds quercetin aglycone and quercetin 3-β-D-glucoside in the QS model bacteriaATCC 12472,PAO1, andMG1. Three phenolic extracts were obtained: red onion extract in methanol acidified with 2.5% acetic acid (RO-1), white onion extract in methanol (WO-1) and white onion extract in methanol ammonium (WO-2). Quercetin 4–glucoside and quercetin 3,4–diglucoside were identified as the predominant compounds in both onion varieties using HPLC-DAD and LC-ESI-MS/MS. However, quercetin aglycone, cyanidin 3–glucoside and quercetin glycoside were identified only in RO-1. The three extracts showed minimum inhibitory concentration (MIC) values equal to or above 125μg/ml of dried extract. Violacein production was significantly reduced by RO-1 and quercetin aglycone, but not by quercetin 3-β-D-glucoside. Motility inPAO1 was inhibited by RO-1, while WO-2 inhibitedMG1 motility only in high concentration. Quercetin aglycone and quercetin 3-β-D-glucoside were effective at inhibiting motility inPAO1 andMG1. Surprisingly, biofilm formation was not affected by any extracts or the quercetins tested at sub-MIC concentrations.studies suggested a better interaction and placement of quercetin aglycone in the structures of the CviR protein ofATCC 12472 than the glycosylated compound which corroborates the better inhibitory effect of the former over violacein production. On the other hand, the two quercetins were well placed in the AHLs binding pockets of the LasR protein ofPAO1. Overall onion extracts and quercetin presented antimicrobial activity, and interference on QS regulated production of violacein and swarming motility.

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PMID: 

J Ethnopharmacol. 2019 Sep 15 ;241:112008. Epub 2019 May 31. PMID: 31158441

Abstract Title: 

Onion bulb extract reduces colitis severity in mice via modulation of colonic inflammatory pathways and the apoptotic machinery.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: The use of nutraceutical-based products has increased in recent years due to their demonstrated efficacy and their good safety profile. Onion is one of the most commonly used plants in the traditional medicine for the management of various conditions including inflammatory and gastrointestinal diseases. However, little is known regarding the molecular mechanism of the anti-inflammatory effects of onion particularly in inflammatory bowel disease (IBD).AIM OF THE STUDY: To test the anti-inflammatory effects of onion bulb extract (OBE) in an IBD mouse model and the molecular mechanisms responsible for these effects such as modulation of the expression and/or the activity profile of various pro-inflammatory molecules.MATERIALS AND METHODS: Colitis was induced in mice by dextran sulfate sodium (DSS) daily administration for 5 days. Animals were sacrificed, colons were removed and the severity of the inflammation was determined by the gross and histological assessments. The colonic level/activity of various cytokines and chemokines were measured using proteome profiling-based assay, western blotting, and immunofluorescence techniques.RESULTS: DSS-induced colitis was significantly reduced by the daily OBE treatment and 5-aminosalicylic acid (5-ASA, positive control), particularly at 100-200 mg/kg doses, at both the gross and histological levels. OBE was also shown to reduce colonic expression and activity of several pro-inflammatory molecules and signaling pathways, such as mitogen activated protein kinase family, mammalian target of rapamycin, cyclooxygenase-2, and tissue inhibitors of metalloproteinases. In addition, OBE reduced the expression of interferon-γ, various C-C and C-X-C chemokines, and molecules involved in the apoptotic machinery such as cytochrome c, caspase-3 and -8, B-cell lymphoma-extra-large and -2.CONCLUSIONS: OBE showed anti-inflammatory actions in IBD mouse model, which is attributed, in part, to the modulation of the expression and the activity of important pro-inflammatory molecules and signaling pathways involved in the inflammatory response. These data suggest that OBE may be a promising lead in the therapeutic management of IBD.

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PMID: 

J Med Food. 2020 Jan ;23(1):37-42. Epub 2019 Dec 19. PMID: 31855493

Abstract Title: 

Onion Peel Extract Increases Erythrocyte Membrane n-3 Fatty Acids in Overweight and Obese Korean Subjects.

Abstract: 

The association between obesity and erythrocyte fatty acids (FAs) has been suggested; however, there have been no studies on the effects of onion peel extract (OPE) on the composition of erythrocyte FAs. This study aimed to investigate the effects of OPE on the composition of erythrocyte FAs in overweight and obese subjects. This was a randomized, double-blind, and placebo-controlled trial conducted in overweight and obese Korean subjects. The placebo and OPE groups were taking placebo capsule or OPE capsule twice per day for 12 weeks. Body composition and fat distribution were measured using dual-energy X-ray absorptiometry. The OPE group showed significantly reduced body weight, body mass index, body fat mass, and percentage of body fat mass. After 12 weeks, eicosapentaenoic acid and monounsaturated FAs of the placebo group were significantly lower at baseline. Consumption of OPE ameliorated the decreasing polyunsaturated n-3 polyunsaturated FA (PUFA) n-3 and increasing PUFA n-6, which prevented an increased n-6/n-3 ratio. The changes in arm fat percentage (ARFATP), trunk fat percentage, and total fat percentage (FATP) were negatively correlated with the change in PUFA n-3. In addition, increased erythrocyte docosahexaenoic acid was associated with decreased ARFATP and FATP. These results suggest that OPE has beneficial effects on obesity by regulating erythrocyte n-6/n-3 ratio and preventing fat accumulation in various body regions.

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PMID: 

J Pharm Pharmacol. 2019 Dec 26. Epub 2019 Dec 26. PMID: 31876957

Abstract Title: 

Beneficial effects of fish oil enriched in omega-3 fatty acids on the development and maintenance of neuropathic pain.

Abstract: 

OBJECTIVE: The aim of this work was to assess the preventive effect of an eicosapentaenoic acid/docosahexaenoic acid-concentrate fish oil on neuropathic pain development and regenerative features of sciatic nerve in rats.METHODS: In the present study, rats with chronic constriction injury (CCI) of the sciatic nerve and sham-operated ones received fish oil enriched in omega-3 fatty acids (0.36 or 0.72 g/kg per day, oral) or saline solution for 21 days, with thermal hyperalgesia and mechanical allodynia being assessed before and 3, 7, 14 and 21 days after injury.KEY FINDINGS: Fish oil enriched in omega-3 fatty acids (0.72 g/kg) reversed thermal hyperalgesia and significantly reduced mechanical allodynia. In addition, ω-3 treatment (0.72 g/kg) promoted the recovery of the Sciatic Functional Index as well as restored axonal density and morphology, without the formation of neuroma in the injured sciatic nerves after21 days.CONCLUSION: We conclude that the fish oil enriched in omega-3 fatty acids administration relieves thermal hyperalgesia and mechanical allodynia effectively and also enhances the recovery process in rats with CCI of the sciatic nerve. These findings might contribute to new therapeutic approaches including omega-3 fatty acids in neuropathic pain treatment.

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PMID: 

Biosci Biotechnol Biochem. 2019 Dec 31:1-14. Epub 2019 Dec 31. PMID: 31889475

Abstract Title: 

Addition of docosahexaenoic acid synergistically enhances the efficacy of apatinib for triple-negative breast cancer therapy.

Abstract: 

The current study aimed to investigate the antitumor and antiangiogenesis effects of apatinib in triple-negative breast cancer in vitro and also whether the combination of docosahexaenoic acid (DHA) and apatinib is more effective than apatinib monotherapy. The cell counting kit-8 assay was used to measure cell proliferation. Flow cytometry was utilized to determine the cell apoptosis rate. A wound healing assay was utilized to assess cell migration. Western blot analysis was carried out to determine the effects of apatinib and DHA on Bcl-2, BAX, cleaved caspase-3, caspase-3, phosphorylated protein kinase B (p-Akt), and Akt expression. DHA in combination with apatinib showed enhanced inhibitory effects on cell proliferation and migration compared with apatinib or DHA monotherapy. Meanwhile, DHA combined with apatinib strongly increased the cell apoptosis percentage. DHA was observed to enhance the antitumor and antiangiogenesis effects of apatinib via further downregulation of p-Akt expression.: FITC: fluorescein isothiocyanate; PI: propidium iodide.

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PMID: 

Front Immunol. 2019 ;10:2851. Epub 2019 Dec 13. PMID: 31921124

Abstract Title: 

Docosahexaenoic Acid Consumption Impedes Early Interferon- and Chemokine-Related Gene Expression While Suppressing Silica-Triggered Flaring of Murine Lupus.

Abstract: 

Exposure of lupus-prone female NZBWF1 mice to respirable crystalline silica (cSiO), a known human autoimmune trigger, initiates loss of tolerance, rapid progression of autoimmunity, and early onset of glomerulonephritis. We have previously demonstrated that dietary supplementation with theω-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) suppresses autoimmune pathogenesis and nephritis in this unique model of lupus flaring. In this report, we utilized tissues from prior studies to test the hypothesis that DHA consumption interferes with upregulation of critical genes associated with cSiO-triggered murine lupus. A NanoString nCounter platform targeting 770 immune-related genes was used to assess the effects cSiOon mRNA signatures over time in female NZBWF1 mice consuming control (CON) diets compared to mice fed diets containing DHA at an amount calorically equivalent to human consumption of 2 g per day (DHA low) or 5 g per day (DHA high). Experimental groups of mice were sacrificed: (1) 1 d after a single intranasal instillation of 1 mg cSiOor vehicle, (2) 1 d after four weekly single instillations of vehicle or 1 mg cSiO, and (3) 1, 5, 9, and 13 weeks after four weekly single instillations of vehicle or 1 mg cSiO. Genes associated with inflammation as well as innate and adaptive immunity were markedly upregulated in lungs of CON-fed mice 1 d after four weekly cSiOdoses but were significantly suppressed in mice fed DHA high diets. Importantly, mRNA signatures in lungs of cSiO-treated CON-fed mice over 13 weeks reflected progressive amplification of interferon (IFN)- and chemokine-related gene pathways. While these responses in the DHA low group were suppressed primarily at week 5, significant downregulation was observed at weeks 1, 5, 9, and 13 in mice fed the DHA high diet. At week 13, cSiOtreatment of CON-fed mice affected 214 genes in kidney tissue associated with inflammation, innate/adaptive immunity, IFN, chemokines, and antigen processing, mostly by upregulation; however, feeding DHA dose-dependently suppressed these responses. Taken together, dietary DHA intake in lupus-prone mice impeded cSiO-triggered mRNA signatures known to be involved in ectopic lymphoid tissue neogenesis, systemic autoimmunity, and glomerulonephritis.

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PMID: 

J Cancer Prev. 2019 Dec ;24(4):233-239. Epub 2019 Dec 30. PMID: 31950023

Abstract Title: 

Docosahexaenoic Acid Inhibits Expression of Fibrotic Mediators in Mice With Chronic Pancreatitis.

Abstract: 

Background: Chronic pancreatitis (CP) is an irreversible progressive disease that destroys exocrine parenchyma, which are replaced by fibrous tissue. As pancreatic fibrosis is a key feature of CP, reducing fibrotic protein content in the pancreas is crucial for preventing CP. Studies suggest that NF-κB facilitates the expression of fibrotic mediators in pancreas and protein kinase C-δ (PKC-δ) regulates NF-κB activation in stimulated pancreatic acinar cells. Docosahexaenoic acid (DHA) is an omega-3 fatty acid having anti-inflammatory and anti-fibrotic effects. It has been shown to inhibit NF-κB activity in cerulein-stimulated pancreatic acinar cells which is a cellular model of CP. In the present study, we investigated if DHA inhibits expression of fibrotic mediators by reducing PKC-δ and NF-κB expression in mouse pancreatic tissues with CP.Methods: For six weeks, mice were weekly induced for acute pancreatitis to develop CP. Furthermore, acute pancreatitis was induced by hourly intraperitoneal injections of cerulein (50μg/kg × 7). Mice were administered DHA (10 μM) via drinking water before and after CP induction.Results: Cerulein-induced pancreatic damages like decreased pancreatic weight/total body weight, leukocyte infiltration, necrosis of acinar cells, and vacuolization were found to be inhibited by DHA. Additionally, DHA inhibited cerulein-induced fibrotic mediators like alpha-smooth muscle actin and fibronectin in pancreas. DHA reduced expression of PKC-δ and NF-κB p65 in pancreatic tissues of cerulein-treated mice.Conclusions: DHA may be beneficial in preventing CP by suppressing pancreatic expression of fibrotic mediators.

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PMID: 

Int J Mol Sci. 2020 Jan 18 ;21(2). Epub 2020 Jan 18. PMID: 31963714

Abstract Title: 

Docosahexaenoic Acid Attenuates Mitochondrial Alterations and Oxidative Stress Leading to Cell Death Induced by Very Long-Chain Fatty Acids in a Mouse Oligodendrocyte Model.

Abstract: 

In the case of neurodegenerative pathologies, the therapeutic arsenal available is often directed towards the consequences of the disease. The purpose of this study is, therefore, to evaluate the ability of docosahexaenoic acid (DHA), a molecule present in certain foods and considered to have health benefits, to inhibit the cytotoxic effects of very long-chain fatty acids (C24:0, C26:0), which can contribute to the development of some neurodegenerative diseases. The effect of DHA (50µM) on very long-chain fatty acid-induced toxicity was studied by several complementary methods: phase contrast microscopy to evaluate cell viability and morphology, the MTT test to monitor the impact on mitochondrial function, propidium iodide staining to study plasma membrane integrity, and DHE staining to measure oxidative stress. A Western blot assay was used to assess autophagy through modification of LC3 protein. The various experiments were carried out on the cellular model of 158N murine oligodendrocytes. In 158N cells, our data establish that DHA is able to inhibit all tested cytotoxic effects induced by very long-chain fatty acids.

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PMID: 

Adv Nutr. 2020 Jan 27. Epub 2020 Jan 27. PMID: 31989167

Abstract Title: 

Docosahexaenoic Acid: Outlining the Therapeutic Nutrient Potential to Combat the Prenatal Alcohol-Induced Insults on Brain Development.

Abstract: 

Brain development is markedly affected by prenatal alcohol exposure, leading to cognitive and behavioral problems in the children. Protecting neuronal damage from prenatal alcohol could improve neural connections and functioning of the brain. DHA, a n-3 (ω-3) long-chain PUFA, is involved in the development of neurons. Insufficient concentrations of DHA impair neuronal development and plasticity of synaptic junctions and affect neurotransmitter concentrations in the brain. Alcohol consumption during pregnancy decreases the maternal DHA status and reduces the placental transfer of DHA to the fetus, resulting in less DHA being available for brain development. It is important to know whether DHA could induce beneficial effects on various physiological functions that promote neuronal development. This review will discuss the current evidence for the beneficial role of DHA in protecting against neuronal damage and its potential in mitigating the teratogenic effects of alcohol.

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PMID: 

World J Clin Cases. 2019 Dec 26 ;7(24):4172-4185. PMID: 31911898

Abstract Title: 

Polyunsaturated fatty acids and DNA methylation in colorectal cancer.

Abstract: 

Colorectal cancer (CRC) has been designated a major global problem, especially due to its high prevalence in developed countries. CRC mostly occurs sporadically (75%-80%), and only 20%-25% of patients have a family history. Several processes are involved in the development of CRC such as a combination of genetic and epigenetic alterations. Epigenetic changes, including DNA methylation play a vital role in the progression of CRC. Complex interactions between susceptibility genes and environmental factors, such as a diet and sedentary lifestyle, lead to the development of CRC. Clinical and experimental studies have confirmed the beneficial effects of dietary polyunsaturated fatty acids (PUFAs) in preventing CRC. From a mechanistic viewpoint, it has been suggested that PUFAs are pleiotropic agents that alter chromatin remodeling, membrane structure and downstream cell signaling. Moreover, PUFAs can alter the epigenomemodulation of DNA methylation. In this review, we summarize recent investigations linking PUFAs and DNA methylation-associated CRC risk.

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