PMID: 

Front Microbiol. 2019 ;10:990. Epub 2019 May 8. PMID: 31134028

Abstract Title: 

Antibiofilm and Antivirulence Efficacies of Flavonoids and Curcumin Against.

Abstract: 

is well adapted to hospital environments, and the persistence of its chronic infections is mainly due to its ability to form biofilms resistant to conventional antibiotics and host immune systems. Hence, the inhibitions of biofilm formation and virulence characteristics provide other means of addressing infections. In this study, the antibiofilm activities of twelve flavonoids were initially investigated. Three most active flavonoids, namely, fisetin, phloretin, and curcumin, dose-dependently inhibited biofilm formation by a referencestrain and by several clinical isolates, including four multidrug-resistant isolates. Furthermore, the antibiofilm activity of curcumin (the most active flavonoid) was greater than that of the well-known biofilm inhibitor gallium nitrate. Curcumin inhibited pellicle formation and the surface motility of. Interestingly, curcumin also showed antibiofilm activity againstand mixed cultures ofand.molecular docking of the biofilm response regulator BfmR showed that the binding efficacy of flavonoids with BfmR was correlated with antibiofilm efficacy. In addition, curcumin treatment diminishedvirulence in anmodel without cytotoxicity. The study shows curcumin and other flavonoids have potential for controlling biofilm formation by and the virulence of.

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PMID: 

Phytomedicine. 2019 May 18 ;62:152964. Epub 2019 May 18. PMID: 31153059

Abstract Title: 

Phloretin suppresses metastasis by targeting protease and inhibits cancer stemness and angiogenesis in human cervical cancer cells.

Abstract: 

BACKGROUND: Phloretin, a dihydrochalcone flavonoid, possesses anti-inflammatory activity and inhibits the growth of various cancers. However, the flavonoid's effect on cervical cancer metastasis and angiogenesis remains unknown.PURPOSE: In this study, we provide molecular evidence associated with the antimetastatic and antiangiogenic effects of phloretin.METHODS: In this study, the anti-invasive effect of phloretin (0-60μM) in cervical cancer cells was evaluated using the Matrigel invasion assay, gelatin zymography, cell-matrix adhesion assay, wound healing assay, and Western blotting. Antiangiogenic potential of phloretin (0-100 μM) was assessed by the Matrigel tube formation assay. The in vivo antitumor effectof phloretin (10 or 20 mg/kg) was fed by oral gavage and determined using subcutaneous inoculation and tail vein injection in immunodeficient nude mice.RESULTS: Phloretin (60μM) showed marked suppression of invasion and migration through downregulation of matrix metalloproteinase (MMP)-2, MMP-3, and cathepsin S in human SiHa cervical cancer cells. Phloretin (60 μM) reversed the epithelial-mesenchymal transition induced by transforming growth factor-β1 and downregulated mesenchymal markers, such as fibronectin, vimentin, and RhoA. Phloretin (100 μM) treatment significantly inhibited the aldehyde dehydrogenase 1 activity of SiHa cells, reduced the self-renewal properties and stemness signatures of CD44 and Sox-2 in sphere-forming cervical cancer-derived tumor-initiating cells, and inhibited the invasion, MMP-2 activity, and tube formation capacity of human umbilical vein endothelial cells. The ability of phloretin (20 mg/kg) to suppress lung metastasis and tumor growth in SiHa cells was evidenced by tail vein injection and subcutaneous inoculation in a tumor xenograft model.CONCLUSION: In summary, the findings indicate that phloretin inhibits the metastatic and angiogenic abilities and cancer stemness of SiHa cells, thereby suggesting that this flavonoid is a promising therapeutic agent for the treatment of human cervical cancer cells.

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PMID: 

Life Sci. 2019 Jun 25:116600. Epub 2019 Jun 25. PMID: 31251998

Abstract Title: 

Phloretin attenuates behavior deficits and neuroinflammatory response in MPTP induced Parkinson's disease in mice.

Abstract: 

Neuroinflammation is one of the significant neuropathological conditions in Parkinson's disease (PD) which is due to microglial and astrocytes activation leads to progressive dopaminergic neuronal loss. To date, Current PD drugs offers only symptomatic relief with adverse effects and lack of ability to prevent the progression of neurodegeneration. Therefore, a better approach to develop a multi potent drug of natural origin would be beneficial in managing the disease. Therefore, the present study aimed to investigate the neuroprotective and anti-inflammatory effects of PHL by exploring its neuroprotective mechanism in 1-methyl-4-phenyl-1,2,3,6-tetrahydro pyridine (MPTP) induced PD in mice. MPTP intoxication in mice cause motor abnormalities, decreased dopamine (DA) levels, reduced tyrosine hydroxylase (TH) enzyme protein expression and inflammation which were effectively restored by PHL. Moreover gliotic specific inflammatory markers like glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor protein-1 (Iba-1), iNOS and COX-2 were found to be expressed more in MPTP intoxicated mice, Further the levels of proinflammatory cytokines like IL-β, IL-6, and TNF-α were significantly upregulated in MPTP intoxicated mice, these deleterious responses were diminished to extend neuroprotection by PHL treatment. Our findings strongly suggest PHL as a potent therapeutic agent in treating PD.

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PMID: 

Exp Cell Res. 2019 Jul 4:111480. Epub 2019 Jul 4. PMID: 31279631

Abstract Title: 

Phloretin and phloridzin improve insulin sensitivity and enhance glucose uptake by subverting PPARγ/Cdk5 interaction in differentiated adipocytes.

Abstract: 

Activators of peroxisome proliferator-activated receptor-γ (PPARγ agonists) are therapeutically promising candidates against insulin resistance and hyperglycemia. Synthetic PPARγ agonists are known to effectively enhance insulin sensitivity, but these are also associated with adverse side-effects and rising cost of treatment. Therefore, natural PPARγtargeting ligands are desirable alternatives for the management of insulin resistance associated with type 2 diabetes. Phloretin (PT) and Phloridzin (PZ) are predominant apple phenolics, which are recognized for their various pharmacological functions. The present study assessed the potential of PTand PZ in enhancing insulin sensitivity and glucose uptake by inhibiting Cdk5 activation and corresponding PPARγ phosphorylation in differentiated 3T3L1 cells. In silico docking and subsequent validation using 3T3L1 cells revealed that PT and PZ not only block the ser273 site of PPARγ but also inhibit the activation of Cdk5 itself, thereby, indicating their potent PPARγ regulatory attributes. Corroborating this, application of PT and PZ significantly enhanced the accumulation of cellular triglycerides as well as expression of insulin-sensitizing genes in adipocytes ultimately resulting in improved glucose uptake. Taken together, the present study reports that PT and PZ inhibit Cdk5 activation, which could be directly influencing the apparent PPARγ inhibition at ser273, ultimately resulting in improved insulin sensitivity and glucose uptake.

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PMID: 

Nutrients. 2019 May 25 ;11(5). Epub 2019 May 25. PMID: 31130634

Abstract Title: 

Role of Apple Phytochemicals, Phloretin and Phloridzin, in Modulating Processes Related to Intestinal Inflammation.

Abstract: 

Plant-derived food consumption has gained attention as potential intervention for the improvement of intestinal inflammatory diseases. Apple consumption has been shown to be effective at ameliorating intestinal inflammation symptoms. These beneficial effects have been related to (poly)phenols, including phloretin (Phlor) and its glycoside named phloridzin (Phldz). To deepen the modulatory effects of these molecules we studied: i) their influence on the synthesis of proinflammatory molecules (PGE, IL-8, IL-6, MCP-1, and ICAM-1) in IL-1β-treated myofibroblasts of the colon CCD-18Co cell line, and ii) the inhibitory potential of the formation of advanced glycation end products (AGEs). The results showed that Phlor (10-50 μM) decreased the synthesis of PGEand IL-8 and the formation of AGEs by different mechanisms. It is concluded that Phlor and Phldz, compounds found exclusively in apples, are positively associated with potential beneficial effects of apple consumption.

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PMID: 

J Med Food. 2019 Jun ;22(6):614-622. Epub 2019 May 6. PMID: 31058564

Abstract Title: 

Chemopreventive Potential of Apple Pulp Callus Against Colorectal Cancer Cell Proliferation and Tumorigenesis.

Abstract: 

This study focused on the evaluation of the chemopreventive potential of tissueculture of the"Mela Rosa Marchigiana"apple (MRM callus) that allows the amplification of secondary metabolites. The MRM pulp and MRM callus chemopreventive potential was evaluated in terms of antiproliferative activity, inhibition of tumorigenesis in soft agar cultures, cell cycle and western blotting analyses in CaCo2 and LoVo colon cancer cell lines and in JB6 promotion-sensitive (JB6 P) cells. MRM callus induced a strong concentration-dependent inhibition of colon cancer cell proliferation and suppressed 12-o-tetra-decanoyl-phorbol-13-acetate-induced tumorigenesis of JB6 Pcells in soft agar cultures. MRM callus inhibited the phosphorylation of JNK, p38, and eIF2alpha. Our data indicate that the MRM callus exerts a good antiproliferative and antitumorigenic potential through the MAP kinase inhibition and could provide natural compounds with chemopreventive properties.

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PMID: 

Int J Food Microbiol. 2019 Mar 2 ;292:101-106. Epub 2018 Dec 21. PMID: 30594741

Abstract Title: 

Antiviral activity of aged green tea extract in model food systems and under gastric conditions.

Abstract: 

Aged-green tea extract (GTE) is known to reduce the infectivity of hepatitis A virus (HAV) and murine norovirus (MNV), a human norovirus surrogate, in vitro and in washing solutions. Initially, the effect of aged-GTE was evaluated on virus like particles (VLPs) of human norovirus (HuNoV) genogroup I (GI) by a porcine gastric mucine (PGM)-enzyme-linked immunosorbent assay (ELISA) and transmission electron microscopy (TEM), and on HuNoV GI suspensions by an in situ capture-RT-qPCR method, suggesting that HuNoVs are very sensitive to aged-GTE treatment at 37 °C. Moreover, the potential application of aged-GTE was evaluated using model foods and simulated gastric conditions. Then, aged-GTE samples prepared in orange juice, apple juice, horchata, and milk, respectively, were individually mixed with each virus and incubated overnight at 37 °C. Aged-GTE at 5 mg/ml in apple juice reduced MNV infectivity to undetectable levels and from 1.0 to 1.8 log in milk, horchata and orange juice. Aged-GTE at 5 mg/ml in orange juice, apple juice, horchata and milk reduced HAV infectivity by 1.2, 2.1, 1.5, and 1.7 log, respectively. Additionally, aged-GTE at 5 mg/ml in simulated intestinal fluid reduced MNV titers to undetectable levels and reduced HAV infectivity by ca. 2.0 log. The results show a potential for aged-GTE as a suitable natural option for preventive strategies for foodborne viral diseases.

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PMID: 

Cytotechnology. 2019 Apr ;71(2):573-581. Epub 2019 Feb 15. PMID: 30771057

Abstract Title: 

Alkali-soluble pectin suppresses IgE production in human myeloma cell line in vitro.

Abstract: 

We found that strawberry (Fragaria x ananassa) extract has an IgE production suppressive activity and its oral administration improved skin manifestation in atopic dermatitis model mice. In present study, we identified an active substance using the IgE-producing human myeloma cell line U266. Gel filtration experiment indicated that the IgE suppressor was more than 6 kDa in molecular size. In addition, its pectinase treatment inhibited the activity, suggesting that the active substance in strawberry extract is pectin. Among solutions of water-(WP), hexametaphosphate-(HXP), acid-(HP) and alkali soluble pectin (OHP) extracted from strawberry, only OHP suppressedIgE production, and their suppressive activity was cancelled by pectinase treatment. In addition, OHP extracted from apple also inhibited IgE production. Furthermore, OHP also suppressed IgE production and did not affect IgG and IgM production in human peripheral blood mononuclear cells in an in vitro immunization condition. From these results, we concluded that OHP was an IgE suppressor in strawberry extract.

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PMID: 

Plant Foods Hum Nutr. 2019 Jul 13. Epub 2019 Jul 13. PMID: 31302831

Abstract Title: 

Apple Phenolic Extracts Strongly Inhibitα-Glucosidase Activity.

Abstract: 

The beneficial health effects of apple consumption are well known, however, little is known about the potential of its phenolic fractions to inhibitα-glucosidases and thereafter to treat diseases related to the carbohydrate metabolism, such as postprandial hyperglycemia and diabetes. In the present study, the α-glucosidase inhibition and antioxidant activity of different phenolic fractions of apple were evaluated using the 2,2-diphenyl-1-picrylhydrazyl and hydroxyl radical scavenging activity. Moreover, the phenolic fractions were chemically characterized by LC-MS in order to identify the compounds responsible for the biological properties. The purified extract (not fractionated) had the highest α-glucosidase and hydroxyl radical inhibitions. The purified extract and fractions III and IV were more active against the enzyme activity than the positive control acarbose, the drug used by diabetic patients to treat postprandial hyperglycaemia. Our results show that apple phenolic extracts strongly inhibit α-glucosidase acitivity, validating their potential to be used in the management of type 2 diabetes.

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PMID: 

Eur J Nutr. 2019 Jul 16. Epub 2019 Jul 16. PMID: 31312904

Abstract Title: 

Modified apple polysaccharide regulates microbial dysbiosis to suppress high-fat diet-induced obesity in C57BL/6J mice.

Abstract: 

PURPOSE: Obesity, substantially increasing the risk of diseases such as metabolic diseases, becomes a major health challenge. In this study, we, therefore, investigated the effect of modified apple polysaccharide (MAP) on obesity.METHODS: Twelve male C57BL/6J mice were given a 45% high-fat diet (HFD) for 12 weeks to replicate an obesity model and six mice were given normal diet as control. Then, 1 g/kg MAP was administrated to six mice by gavage for 15 days. Illumina Miseq PE300 sequencing platform was used to analyze the microbial diversity of fecal samples. Flow cytometry was employed to investigate the effects of MAP on immune cells in adipose tissue. Bacterial culture and qPCR were used to assess the effects of MAP on the growth of whole fecal bacteria and representative microbiota in vitro.RESULTS: MAP could alleviate HFD-induced obesity and decrease body weight of mice effectively. The results ofα diversity showed that Shannon index in HFD group was significantly lower than that in control group; Shannon index in MAP group was higher than that in HFD group. The results of β diversity showed that the microbiota of MAP group was more similar to that of control group. HFD increased the number of T cells and macrophages in adipocytes; while MAP decreased the number of T cells and macrophages. MAP could promote the growth of fecal bacteria, and demonstrated a facilitated effect on the proliferation of Bacteroidetes, Bacteroides, Lactobacillus, and an inhibitory effect on Fusobacterium.CONCLUSIONS: MAP could reduce HFD-induced obesity of mice effectively. The possible mechanisms are that MAP restored HFD-induced intestinal microbiota disorder, downregulated the number of T cells and macrophages in adipose tissue.

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