PMID: 

Can J Physiol Pharmacol. 2019 Sep 27. Epub 2019 Sep 27. PMID: 31560861

Abstract Title: 

β-sitosterol mitigates the progression of high-fructose diet-induced non-alcoholic fatty liver disease in growing male Sprague-Dawley rats.

Abstract: 

Fructose contributes to the development of non-alcoholic fatty liver disease (NAFLD).β-sitosterol (Bst), a naturally occurring phytosterol, has antihyperlipidaemic and hepatoprotective properties. This study interrogated the potential protective effect of β-sitosterol against NAFLD in growing rats fed a high-fructose diet, modelling children fed obesogenic diets. Forty-four 21-dayold male rat pups were randomly allocated to and administered the following treatments for 12 weeks: group I- standard rat chow (SRC) + plain drinking water (PW) + plain gelatine cube (PC); group II- SRC+ 20% w/v fructose solution (FS) as drinking fluid + PC; group III- SRC + FS + 100 mg/kg fenofibrate in gelatine cube; group IV- SRC + FS + 20 mg/kg β-sitosterol gelatine cube (Bst) and group V- SRC + PW + Bst. Terminally, the livers were dissected out, weighed, total liver lipid content determined and histological analyses were done. Harvested plasma was used to determine the surrogate biomarkers of liver function. The high-fructose diet caused increased (p10% liver mass), micro- and macro-vesicular hepatic steatosis and hepatic inflammation.β-sitosterol and fenofibrate prevented the high-fructose diet-induced macrovesicular steatosis and prevented the progression of NAFLD to steatohepatitis. β-sitosterol can prospectively be used to mitigate diet-induced NAFLD.

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PMID: 

Eur J Nutr. 2019 Oct 28. Epub 2019 Oct 28. PMID: 31659451

Abstract Title: 

Anti-obesity effect of Lactobacillus rhamnosus LS-8 and Lactobacillus crustorum MN047 on high-fat and high-fructose diet mice base on inflammatory response alleviation and gut microbiota regulation.

Abstract: 

PURPOSE: The objective of the study was to evaluate the anti-obesity effect of Lactobacillus rhamnosus LS-8 and Lactobacillus crustorum MN047, and illustrate the potential functional mechanism about the alleviation of high fat and high fructose diet (HFFD) induced obesity and related metabolic abnormalities.METHODS: C57BL/6J mice were subjected to a standard or HFFD with or without supplementation of L. rhamnosus LS-8 and L. crustorum MN047 for 10 weeks. Obesity related metabolic indices including glucose tolerance, insulin resistance, serum lipid, liver function, hormones and inflammatory cytokines were assessed by standard protocols. For the monitoring of inflammatory response and lipid metabolism, transcriptional levels were profiled inliver and/or adipose tissues. Furthermore, gut microbiota composition analyses in the fecal samples were performed using 16S rRNA gene sequencing, and gut microbial metabolites, including lipopolysaccharide (LPS) and short-chain fatty acids (SCFAs), were also tested for the assessment of the relationship between gut microbiota variation and inflammatory response.RESULTS: Administration with L. rhamnosus LS-8 and L. crustorum MN047 significantly mitigated body weight gain and insulin resistance, and inflammatory response (TNF-α, IL-1β and IL-6 levels in serum and corresponding mRNA levels in adipose tissues) was significantly inhibited in these two strains-treated mice. Moreover, L. rhamnosus LS-8 and L. crustorum MN047 could partially normalized mRNA expression levels involved in lipid metabolism including Pparγ, Srebp-1c, CD36, Fabp2 and FAS. In addition, these two strains manipulated gut microbiota by decreasing the abundance of Bacteroides and Desulfovibrio and increasing that of Lactobacillus and Bifidobacterium, which in turn raised the levels of feces SCFAs and lowered the levels of circulating LPS.CONCLUSION: These results indicated that L. rhamnosus LS-8 and L. crustorum MN047 supplementation possessed the anti-obesity effect on the HFFD fed mice by alleviating inflammatory response and regulating gut microbiota, which further suggested that these two probiotics can be considered as an alternative dietary supplement in combination with the preventive and therapeutic strategies against obesity and related complications.

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PMID: 

Eur J Pharmacol. 2019 Oct 5 ;860:172568. Epub 2019 Jul 23. PMID: 31348906

Abstract Title: 

Antitumor and apoptotic effects of quercetin on human melanoma cells involving JNK/P38 MAPK signaling activation.

Abstract: 

In this study, we investigated whether Quercetin has anti-cancer effects on A375SM and A375P human melanoma cells. Cell viability was assessed using an MTT assay. The proliferation of melanoma cells was measured by a wound-healing assay. Quercetin significantly decreased viability and proliferation of A375SM cells in a concentration-dependent manner. However, quercetin had no effect on A375P cells. DAPI staining showed increased chromatin condensation in a concentration-dependent manner, indicating apoptosis. Flow cytometric analysis indicated that quercetin suppressed the viability of A375SM cells by inducing apoptosis. Expression of quercetin-induced apoptosis proteins was investigated by Western blot analysis. Quercetin increased the expression of Bax, phospho-JNK, phospho-p38 and phospho-ERK1/2, cleaved poly-ADP ribose polymerase and decreased Bcl-2 in a concentration-dependent manner. We also investigated the in vivo tumor-growth inhibitory effect of quercetin. Quercetin (at 50 and 100 mg/kg) significantly decreased the A375SM tumor volume compared to the control group and increased apoptosis as assessed by the TUNEL assay. Immunohistochemistry staining revealed that the level of phosphor-JNK and phosphor-p38 increased in the quercetin-treated mice. These results indicate thatquercetin inhibited the growth of A375SM melanoma cells through apoptosis and thus can be regarded as a new and effective chemo-preventive or therapeutic agent.

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PMID: 

Reprod Biol. 2019 Sep ;19(3):245-254. Epub 2019 Aug 3. PMID: 31383475

Abstract Title: 

Quercetin protects human granulosa cells against oxidative stress via thioredoxin system.

Abstract: 

Granulosa Cells (GCs) are sensitive to excessive production of reactive oxygen species (ROS). Quercetin (QUR) is a free radical scavenger which can alleviate oxidative stress through nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/antioxidant response element (ARE) pathway and thioredoxin (Trx) system. We aimed to explore the probable protective role of QUR on cultured human GCs treated with hydrogen peroxide (HO) as an inducer of oxidative stress. MTT assay was applied for evaluating the cell cytotoxicity of QUR and HO. The rate of apoptotic cells and intracellular ROS generation were determined by Annexin V-FITC/PI staining and 2'-7'-dichlorodihydrofluorescein diacetate fluorescent probes (DCFH-DA), respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis and western blot analysis were used to evaluate the gene and protein expression of Nrf2 and kelch-like ech-associated protein 1 (Keap1)1. The Nrf2 and Trx activities were measured by Enzyme-linked Immunosorbent Assay (ELISA). The results indicated that QUR pretreatment can decrease ROS production and apoptosis induced by HO. In addition, QUR increased Nrf2 gene and protein expression, as well as its nuclear translocation. Moreover, in QUR-treated group, a lower level of Keap1 protein was observed, which was not reported as significant. The results also indicated a significant correlation between the expression of Nrf2 and Keap1 in QUR-treated group. Further, QUR protected GCs from oxidative stress by increasing Trx gene expression and activity. This study suggests that QUR as a supplementary factor may protect GCs from oxidative stress in diseases related to this condition.

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PMID: 

Phytother Res. 2019 Aug 26. Epub 2019 Aug 26. PMID: 31452288

Abstract Title: 

Quercetin improves nonalcoholic fatty liver by ameliorating inflammation, oxidative stress, and lipid metabolism in db/db mice.

Abstract: 

Multiphase pathological processes involve in Type 2 diabetes (T2DM)-induced nonalcoholic fatty liver disease (NAFLD). However, the therapies are quite limited. In the present study, the hepatoprotective effects and underlying mechanisms of quercetin in T2DM-induced NAFLD were investigated. T2DM-induced NAFLD and quercetin treatment models were established in vivo and in vitro. The results revealed that quercetin alleviated serum transaminase levels and markedly reduced T2DM-induced histological alterations of livers. Additionally, quercetin restored superoxide dismutase, catalase, and glutathione content in livers. Not only that, quercetin markedly attenuated T2DM-induced production of interleukin 1 beta, interleukin 6, and TNF-α. Accompanied by the restoration of the increased serum total bile acid (p = .0001) and the decreased liver total bile acid (p = .0005), quercetin could reduce lipid accumulation in the liver of db/db mice. Further mechanism studies showed that farnesoid X receptor 1/Takeda G-protein-coupled receptor 5 signaling pathways was involved in quercetin regulation of lipid metabolism in T2DM-induced NAFLD. In high D-glucose and free fatty acid cocultured HepG2 cells model, quercetin eliminated lipid droplets and restored the upregulated total cholesterol and triglyceride levels. Similar to the findings in mice, quercetin could also activate farnesoid X receptor 1/Takeda G-protein-coupled receptor 5 signaling pathway. These findings suggested that quercetin might be a potentially effective drug for the treatment of T2DM-induced NAFLD.

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PMID: 

Melanoma Res. 2019 Oct 22. Epub 2019 Oct 22. PMID: 31651714

Abstract Title: 

Anti-angiogenic effects of mangiferin and mechanism of action in metastatic melanoma.

Abstract: 

Advanced metastatic melanoma, one of the most aggressive skin malignancies, is currently without reliable therapy. The process of angiogenesis is crucial for progression and metastasis of the majority of solid tumors including melanomas. Therefore, new therapies are urgently needed. Mangiferin is a naturally occurring glucosylxanthone which exerts many pharmacological activities against cancer-inflammation. However, the effect of mangiferin on metastasis and tumor growth of metastatic melanoma remains unclear. In this study, we demonstrate that mangiferin interferes with inflammation, lipid and calcium signaling which selectively inhibits multiple NFkB target genes including interleukin-6, tumor necrosis factor, interferon gamma, vascular endothelial growth factor receptor 2, plasminogen activator urokinase, matrix metalloprotease 19, C-C Motif Chemokine Ligand 2 and placental growth factor. This abrogates angiogenic and invasive processes and capillary tube formation of metastatic melanoma cells as well as human placental blood vessel explants in-vitro and blocks angiogenesis characteristic of the chicken egg chorioallantoic membrane assay and in melanoma syngeneic studies in vivo. The results obtained in this research illustrate promising anti-angiogenic effects of the natural glucosylxanthone mangiferin for further (pre)clinical studies in melanoma cancer patients.

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PMID: 

Nutrients. 2019 Oct 28 ;11(11). Epub 2019 Oct 28. PMID: 31661850

Abstract Title: 

A Single Dose of The Mango Leaf Extract Zynamitein Combination with Quercetin Enhances Peak Power Output During Repeated Sprint Exercise in Men and Women.

Abstract: 

The mango leaf extract rich in mangiferin Zynamiteimproves exercise performance when combined with luteolin or quercetin ingested at least 48 h prior to exercise. To determine whether a single dose of Zynamiteadministered 1 h before exercise increases repeated-sprint performance, 20 men and 20 women who were physically active were randomly assigned to three treatments following a double-blind cross-over counterbalanced design. Treatment A, 140 mg of Zynamite, 140 mg of quercetin, 147.7 mg of maltodextrin, and 420 mg of sunflower lecithin; Treatment B, 140 mg of Zynamite, 140 mg of quercetin, and 2126 mg of maltodextrin and Treatment C, 2548 mg of maltodextrin (placebo). Subjects performed three Wingate tests interspaced by 4 min and a final 15 s sprint after ischemia. Treatments A and B improved peak power output during the first three Wingates by 2.8% and 3.8%, respectively (treatment x sprint interaction,= 0.01). Vastus Lateralis oxygenation (NIRS) was reduced, indicating higher Oextraction (treatment× sprint interaction,= 0.01). Improved Oextraction was observed in the sprints after ischemia (= 0.008; placebo vs. mean of treatments A and B). Blood lactate concentration was 5.9% lower after the ingestion of Zynamite® with quercetin in men (treatment by sex interaction,= 0.049). There was a higher Vastus Lateralis Oextraction during 60 s ischemia with polyphenols (treatment effect,= 0.03), due to the greater muscle VOin men (= 0.001). In conclusion, a single dose of Zynamitecombined with quercetin one hour before exercise improves repeated-sprint performance and muscle Oextraction and mitochondrial Oconsumption during ischemia. No advantage was obtained from the addition of phospholipids.

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PMID: 

Int J Mol Sci. 2019 Sep 2 ;20(17). Epub 2019 Sep 2. PMID: 31480735

Abstract Title: 

Quercetin Enhances the Anti-Tumor Effects of BET Inhibitors by Suppressing hnRNPA1.

Abstract: 

Bromodomain and extraterminal domain (BET) proteins, which are important epigenetic readers, are often dysregulated in cancer. While a number of BET inhibitors are currently in early phase clinical trials, BET inhibitors show limited single-agent activity. The purpose of this study is to determine if Quercetin, a naturally occurring polyphenolic flavonoid often found abundant in fruits and vegetables, can enhance the anti-tumor effects of BET inhibitors. The efficacy of the combination was evaluated in vitro and in a xenograft model of pancreatic cancer. Co-treatment with BET inhibitors and Quercetin promoted apoptosis, decreased sphere-forming ability by cancer cells, and decreased cell proliferation. We found that hnRNPA1, a nuclear protein known to control mRNA export and mRNA translation of anti-apoptotic proteins, mediates some anti-tumor effects by Quercetin. Additionally, we show that combining BET inhibitors with Quercetin or hnRNPA1 knockdown decreased the anti-apoptotic protein Survivin. Significantly, Quercetin decreased hnRNPA1 in vivo and enhanced the effects of BET inhibitors at suppressing tumor growth. Together, these results demonstrate that Quercetin enhances the efficacy of BET inhibitors by suppressing hnRNPA1, and identify combination therapy with Quercetin and BET inhibitors for the treatment of cancer patients.

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PMID: 

J Agric Food Chem. 2019 Oct 2 ;67(39):10863-10870. Epub 2019 Sep 19. PMID: 31507180

Abstract Title: 

Allicin Inhibited-Induced Mastitis by Reducing Lipid Raft Stability via LxRα in Mice.

Abstract: 

Mastitis, inflammation of the mammary gland, occurs in both humans and animals.is the most common infectious bacterial pathogen associated with mastitis. We investigated the effects of allicin on-induced mastitis in mice. Pathological histology revealed that allicin inhibited-induced pathological damage and myeloperoxidase activity in mammary tissues. Enzyme-linked immunosorbent assays demonstrated that allicin reduced the production of IL-1β and TNF-α as well as inhibited the NF-κB and mitogen-activated protein kinase pathway by reducing phosphorylation of p65, IκBα, p38, JNK, and ERK. Western blotting revealed that allicin reduced TLR2 and TLR6 expression in mammary tissues and cells but not in HEK293 cells. The lipid raft content was reduced by allicin, which inhibited signaling downstream of TLR2 and TLR6. Liver X receptor α (α) luciferase reporter assays andα interference experiments showed that allicin improved theα activity and adenosine 5'-triphosphate-binding cassette G and A1 (ABCG and ABCA1) expression, thereby reducing the cholesterol level, lipid raft formation, and downstream TLR2 and TLR6 pathway activity. These results demonstrated that allicin exerted anti-inflammatory effects againstmastitis by improving theα activity and reducing lipid raft formation.

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PMID: 

World J Gastroenterol. 2019 Oct 21 ;25(39):6025-6040. PMID: 31660038

Abstract Title: 

Allicin as add-on therapy forinfection: A systematic review and meta-analysis.

Abstract: 

BACKGROUND: Allicin (2-propene-1-sulfinothioic acid S-2-propenyl ester, diallyl thiosulfinate) extracted from garlic, has proven activity against() infection. In recent years, clinical trials have explored its utility as an add-on therapy with variable outcomes reported.AIM: To perform a systemic review of allicin as an add-on treatment forinfection and assess its efficacy in randomized controlled trials (RCTs).METHODS: Electronic databases including MEDLINE, EMBASE, the Web of Science, the Cochrane Database, the China National Knowledge Infrastructure Database, Chinese VIP Information Databases, Chinese Medical Databases, and the Wan-Fang Database were searched for keywords including"allicin","","randomized clinical trials", and their synonyms. A meta-analysis was performed using the fixed-effects model for low heterogeneity and the random-effects model for high heterogeneity with sensitivity analysis. Bias was evaluated using Egger's tests. Trial sequential analysis (TSA) was used to evaluate information size and treatment benefits. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess the level of quality, and studies were classed as"high quality","moderate quality","low quality", and"very low quality".RESULTS: A total of eight RCTs consisting of 867 participants (435 from the allicin group and 432 from the control group) were included. Eradication rate in the allicin group (93.33%, 406/435) was significantly higher than that of the control group (83.56%, 361/432) [= 0%, odds ratio (OR) = 2.75, 95% confidence interval (CI): 1.74-4.35,

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