PMID: 

IUBMB Life. 2020 Feb 6. Epub 2020 Feb 6. PMID: 32027086

Abstract Title: 

Quercetin radiosensitizes non-small cell lung cancer cells through the regulation of miR-16-5p/WEE1 axis.

Abstract: 

BACKGROUND: Quercetin, a widely distributed bioflavonoid, plays a role in combating diverse human cancers including non-small cell lung cancer (NSCLC). However, the role of quercetin in reversing the radioresistance of NSCLC cells and its underlying mechanism are far from being elucidated.METHOD: Radiation-resistant NSCLC cell lines were established. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of miR-16-5p and WEE1 G2 checkpoint kinase (WEE1) mRNA in radiation-resistant cells. After being treated with different concentrations of quercetin and different doses of X-ray, cell proliferation and apoptosis were monitored by CCK-8 assay, colony formation assay, and flow cytometry, respectively. Ultimately, the targeting relationship between miR-16-5p and WEE1 was verified via a dual fluorescent reporter gene assay.RESULTS: The expression of miR-16-5p was down-regulated in radiation-resistant cells, while the expression of WEE1 was up-regulated. Quercetin enhanced the radiosensitivity of NSCLC cells in a dose- and time-dependent manner. Furthermore, quercetin treatment increased the expression of miR-16-5p and decreased the expression of WEE1. The function of quercetin was reversed by miR-16-5p inhibitors or the transfection of WEE1 overexpressing plasmids.CONCLUSION: In conclusion, quercetin enhanced the radiosensitivity of NSCLC cells via modulating the expression of miR-16-5p and WEE1.

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PMID: 

Arch Biochem Biophys. 2020 Mar 30 ;682:108296. Epub 2020 Feb 4. PMID: 32032576

Abstract Title: 

Quercetin suppresses the migration of hepatocellular carcinoma cells stimulated by hepatocyte growth factor or transforming growth factor-α: Attenuation of AKT signaling pathway.

Abstract: 

Flavonol, which is found abundantly in plants such as fruits and vegetables, belongs to the family of flavonoid, natural polyphenols. Quercetin, one of the flavonol, reportedly has anti-cancer effects and prevents the proliferation of various cancer cells, including hepatocellular carcinoma (HCC). However, the effects of quercetin on HCC cells migration have not yet been clarified. We have previously shown that the migration of human HCC-derived HuH7 cells induced by hepatocyte growth factor (HGF) or transforming growth factor-α (TGF-α) is mediated through p38 MAPK and AKT. In this study, we investigated whether quercetin affects the HGF- or TGF-α-induced migration of HuH7 cells. Quercetin significantly suppressed both HGF- and TGF-α-induced migration of HuH7 cells in a dose-dependent manner. In addition, myricetin, another flavonol, also showed significant inhibition of the cell migration. Each HGF- and TGF-α-induced autophosphorylation of receptors were not affected by quercetin or myricetin. Quercetin did not suppress HGF- or TGF-α-induced p38 MAPK phosphorylation. On the contrary, quercetin and myricetin inhibited the growth factors-induced phosphorylation of AKT. Our results strongly suggest that quercetin suppresses the growth factor-induced migration of HCC cells by inhibiting the signaling pathway of AKT but not p38 MAPK.

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PMID: 

Molecules. 2020 Feb 10 ;25(3). Epub 2020 Feb 10. PMID: 32050534

Abstract Title: 

Quercetin Inhibits Cell Survival and Metastatic Ability via the EMT-mediated Pathway in Oral Squamous Cell Carcinoma.

Abstract: 

This study aimed to investigate whether quercetin exerts anticancer effects on oral squamous cell carcinoma (OSCC) cell lines and to elucidate its mechanism of action. These anticancer effects in OSCC cells were assessed using an MTT assay, flow cytometry (to assess the cell cycle), wound-healing assay, invasion assay, Western blot analysis, gelatin zymography, and immunofluorescence. To investigate whether quercetin also inhibits transforming growth factorβ1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) in human keratinocyte cells, HaCaT cells were treated with TGF-β1. Overall, our results strongly suggest that quercetin suppressed the viability of OSCC cells by inducing cell cycle arrest at the G2/M phase. However, quercetin did not affect cell viability of human keratinocytes such as HaCaT (immortal keratinocyte) and nHOK (primary normal human oral keratinocyte) cells. Additionally, quercetin suppresses cell migration through EMT and matrix metalloproteinase (MMP) in OSCC cells and decreases TGF-β1-induced EMT in HaCaT cells. In conclusion, this study is the first, to our knowledge, to demonstrate that quercetin can inhibit the survival and metastatic ability of OSCC cells via the EMT-mediated pathway, specifically Slug. Quercetin may thus provide a novel pharmacological approach for the treatment of OSCCs.

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PMID: 

Sci Rep. 2020 Feb 12 ;10(1):2440. Epub 2020 Feb 12. PMID: 32051470

Abstract Title: 

Quercetin liposomes ameliorate streptozotocin-induced diabetic nephropathy in diabetic rats.

Abstract: 

The effects of quercetin liposomes (Q-PEGL) on streptozotocin (STZ)-induced diabetic nephropathy (DN) was investigated in rats. Male Sprague Dawley rats were used to establish a STZ induced DN model. DN rats randomly received one of the following treatments for 8 weeks: blank treatment (DN), free quercetin (Que), pegylated liposomes (PEGL) and pegylated quercetin liposomes (Q-PEGL). A group of healthy rats served as the normal control. The fasting blood glucose (FBG), body weights (BWs), renal hypertrophy index (rHI), serum and urine biochemistry, renal histopathology, oxidative stress and immunohistochemical measurements of AGEs were analyzed to compare the effect of different treatments. Que and Q-PEGL significantly improved DN biochemistry and pathological changes, although the treated rats still had some symptoms of DN. The therapeutic effect of Q-PEGL surpassed that of Que. Pegylated quercetin liposomes allow maintaining higher quercetin concentrations in plasma than non-encapsulated quercetin. In conclusion the use of quercetin liposomes allows to reduce disease symptoms in a rat model of DN.

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PMID: 

J Food Biochem. 2020 Feb 17:e13164. Epub 2020 Feb 17. PMID: 32065675

Abstract Title: 

Quercetin is protective against short-term dietary advanced glycation end products intake induced cognitive dysfunction in aged ICR mice.

Abstract: 

Dietary advanced glycation end products (dAGEs) might be potential toxins involved in the pathogenesis of Alzheimer's disease (AD). Quercetin is a flavonoid possessing neuroprotective effects. We aimed to explore whether a 21 days of dAGEs intake would result in cognitive dysfunction in aged ICR mice, and the protective effects of quercetin, with potential mechanisms explored. Fourteen-month old ICR mice were randomly assigned into four groups, that is, Control, AGEs, quercetin, and AGE diet supplemented with quercetin. Key markers involved in Aβ, tau, and neuroinflammation from hippocampus and cortex were measured via western blot. Gut microbiota and short chain fatty acids profiles from intestinal contents were measured via 16S rRNA gene sequencing and gas chromatography (GC), respectively. Quercetin alleviated cognitive impairment induced by dAGEs in aged mice. This might be associated with that quercetin reduced cathepsin B, tau phosphorylation, and neuroinflammation, and elevated α-diversity index (ACE, Chao1, and Shannon index), and reduced phylum Verrucomicrobia of gut microbiota. PRACTICAL APPLICATIONS: Alzheimer's disease (AD) has been regarded as the commonest cause of progressive dementia for the elderly. This study is the very first to demonstrate that even a short-term dietary advanced glycation end product (dAGEs) intake induced impaired cognitive function in aged ICR mice, and querectin is capable of reversing dAGEs-induced cognitive dysfunction. Reduced tau phosphorylation, neuroinflammation, and altered gut microbiota profiles may be involved in querectin's protective effects against dAGEs-induced cognitive impairment. Our study suggested that quercetin supplementation might be beneficial for improving cognitive function in elderly subjects with high consumption of dAGEs such as grilling, frying, and broiling of food.

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PMID: 

Biofactors. 2020 Feb 20. Epub 2020 Feb 20. PMID: 32078205

Abstract Title: 

Quercetin alleviates hyperthyroidism-induced liver damage via Nrf2 Signaling pathway.

Abstract: 

Quercetin is a plant flavonoid and has antioxidative properties. In this study, we evaluated the therapeutic effect of quercetin on thyroid dysfunction in L-thyroxin (LT4)-induced hyperthyroidism rats. LT4 was used to prepare the experimental hyperthyroidism model via the intraperitoneal injection. Quercetin was injected at a series doses (5, 50, and 100 mg/kg) to LT4-induced hypothyroidism rats once a day for 14 days. The body weight and food intake were measured once a week. The levels of thyroid hormones, liver function, oxidative stress markers, and antioxidant markers were measured using commercial enzyme-linked immunosorbent assay kits. Hematoxylin-eosin staining was used to observe the thyroid tissue histological changes. The levels of nuclear and total nuclear factor erythroid 2-related factor 2 (Nrf2) were determined by western blot. The liver oxidative stress markers in LT4-induced hyperthyroidism Nrf2 knockout rats were determined to evaluate the role of Nrf2 on quercetin induced protective effects. LT4 administration increased the levels of serum triiodothyronine and thyroxine, activity of oxidative stress markers with a parallel decrease in antioxidant markers and Nrf2. However, the simultaneous administration of quercetin, reversed all these effects indicating its potential in the regulation of hyperthyroidism. Furthermore, the loss function of Nrf2 diminished these effects resulting from the quercetin application, indicating the inhibitory effects caused by the quercetin may be involved in Nrf2 signaling pathway. These results indicate that quercetin could be used to protect against experimental hyperthyroidism-induced liver damage via Nrf2 signaling pathway.

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PMID: 

J Agric Food Chem. 2020 Feb 26 ;68(8):2381-2392. Epub 2020 Feb 18. PMID: 32037817

Abstract Title: 

Inhibitory Effects of Walnut () Peptides on Neuroinflammation and Oxidative Stress in Lipopolysaccharide-Induced Cognitive Impairment Mice.

Abstract: 

Increasing level of inflammation and oxidative stress could lead to memory impairment. The purpose of this study was to determine the neuroprotective effects of walnut peptides against memory deficits induced by lipopolysaccharide (LPS) in mice and further to explore the underlying anti-inflammatory mechanisms against LPS-elicited inflammation in BV-2 cells. Results showed that walnut protein hydrolysate (WPH) and its low-molecular-weight fraction (WPHL) could ameliorate the memory deficits induced by LPS via normalizing the inflammatory response and oxidative stress in brain, especially WPHL. Furthermore, 18 peptides with anti-inflammatory activities on LPS-activated BV-2 cells were identified from WPHL and it was found that Trp, Gly, and Leu residues in peptides might contribute to the anti-inflammation. Meanwhile, the strong anti-inflammatory effects of LPF, GVYY, and APTLW might be related to their hydrophobic and aromatic amino acid residues as well. LPF, GVYY, and APTLW could reduce the content of proinflammatory mediators and cytokines by downregulating related enzyme expressions and mRNA expressions. Additionally, ROS and mitochondria homeostasis might also contribute to their anti-inflammatory effects.

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PMID: 

Nutrients. 2020 Feb 20 ;12(2). Epub 2020 Feb 20. PMID: 32093220

Abstract Title: 

Beneficial Effects of Walnuts on Cognition and Brain Health.

Abstract: 

Oxidative stress and neuroinflammation have important roles in the aging process, mild cognitive impairment (MCI), Alzheimer's disease (AD), and other brain disorders. Amyloid beta protein (Aβ) is the main component of amyloid plaques in the brains of people with AD. Several studies suggest that Aβ increases the generation of free radicals in neurons, which leads to oxidative damage and cell death. Aβ can also induce neuroinflammation by increasing pro-inflammatory cytokines and enzymes. Walnuts contain several components that have antioxidant and anti-inflammatory effects. Animal and human studies from our and other groups suggest that supplementation with walnuts in the diet may improve cognition and reduce the risk and/or progression of MCI and AD. In the transgenic AD mousemodel (AD-tg), we have reported the beneficial effects of a diet with walnuts on memory, learning, motor coordination, anxiety, and locomotor activity. Human clinical trials have also suggested an association of walnut consumption with better cognitive performance and improvement in memory when compared to baseline in adults. Our recent study in AD-tg mice has shown that a walnut-enriched diet significantly improves antioxidant defense and decreases free radicals' levels, lipid peroxidation, and protein oxidation when compared to a control diet without walnuts. These findings suggest that a diet with walnuts can reduce oxidative stress by decreasing the generation of free radicals and by boosting antioxidant defense, thus resulting in decreased oxidative damage to lipids and proteins. An in vitro study with synthetic Aβ showed that walnut extract can inhibit Aβ fibrillization and solubilize the preformed Aβ fibrils, suggesting an anti-amyloidogenic property of walnuts. Because it takes many years for cognitive impairment and dementia to develop, we suggest that early and long-term dietary supplementation with walnuts may help to maintain cognitive functions and may reduce the risk of developing, or delay the onset and/or slow the progression of, MCI and dementia by decreasing Aβ fibrillization, reducing oxidative damage, increasing antioxidant defense, and decreasing neuroinflammation. Furthermore, several animal and human studies have suggested that walnuts may also decrease the risk or progression of other brain disorders such as Parkinson's disease, stroke, and depression, as well as of cardiovascular disease and type 2 diabetes. Together, these reports suggest the benefits of a walnut-enriched diet in brain disorders and in other chronic diseases, due to the additive or synergistic effects of walnut components for protection against oxidative stress and inflammation in these diseases.

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PMID: 

J Agric Food Chem. 2020 Feb 22. Epub 2020 Feb 22. PMID: 32090563

Abstract Title: 

Neuroprotection by Walnut-derived Peptides through Autophagy Promotion via Akt/mTOR Signaling Pathway against Oxidative Stress in PC12 Cells.

Abstract: 

Natural-derived peptides are effective substances in attenuating oxidative stress. However, their specific mechanisms have not been fully elucidated, especially in peptide-mediated autophagy. In the present study, TWLPLPR, YVLLPSPK, and KVPPLLY, novel peptides fromMaxim, prevented ROS production, elevated GSH-Px activity and ATP levels, and ameliorated apoptosis in Aβ(at concentration of 50μM for 24 h) induced PC12 cells (

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PMID: 

Int J Vitam Nutr Res. 2019 Sep ;89(3-4):161-167. Epub 2019 Apr 16. PMID: 30987551

Abstract Title: 

Alpha lipoic acid supplementation improved antioxidant enzyme activities in hemodialysis patients.

Abstract: 

Cardiovascular disease (CVD) is the main cause of death in hemodialysis (HD) patients and oxidative stress is an important risk factor for CVD. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) are primary antioxidant enzymes in human cells acting against toxic reactive oxygen species (ROS) and their reduced activity may contribute to oxidative disorders in HD patients. Alpha lipoic acid (ALA) as a potent strong antioxidant may affect these enzymes.We examined the effects of ALA supplementation on antioxidant enzyme activities in HD patients.In this double-blinded, randomized clinical trial, 63 HD patients (43 males and 20 females; age range: 22-79 years) were assigned into the ALA group (n: 31), receiving a daily dose of ALA (600 mg), or a control group (n: 32), receiving placebo for 8 weeks. Body mass index (BMI), antioxidant enzymes, albumin (Alb) and hemoglobin (Hb) were determined before and after intervention.At baseline, the mean blood activities of SOD, GPx, and CAT in ALA group were 1032±366, 18.9±5.09 and 191±82.7 U/gHb which increased at the end of study to 1149±502, 19.1±7.19 and 208±86.6 U/gHb respectively. However, only the increase of SOD was statistically significant in comparison with placebo group (P = 0.04). The mean levels of Alb, Hb, weight and BMI were not significantly changed in study groups (P>0.05).ALA may be beneficial for HD patients by increasing the activity of antioxidant enzymes; however, further studies are needed to achieve precise results.

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