PMID: 

Biomed Res Int. 2020 ;2020:1315202. Epub 2020 Jan 8. PMID: 31998777

Abstract Title: 

Comparative Study on Beneficial Effects of Hydroxytyrosol- and Oleuropein-Rich Olive Leaf Extracts on High-Fat Diet-Induced Lipid Metabolism Disturbance and Liver Injury in Rats.

Abstract: 

Oleuropein and hydroxytyrosol, as major compounds of olive leaves, have been reported to exert numerous pharmacological properties, including anticancer, antidiabetic, and anti-inflammatory activities. The purpose of this study is to evaluate and compare the protective effect of oleuropein- and hydroxytyrosol-rich extracts, derived from olive leaves, on high-fat diet-induced lipid metabolism disturbance and liver injury in rats. In this respect, four groups of male rats (8 per group) were used: control group (Control), group treated with high-fat diet (HFD), group treated with HFD and oleuropein (HFD + OLE), and group treated with HFD and hydroxytyrosol (HFD + HYD). The current research showed that the treatment with the HFD increased the body weight and adipose tissue mass in male rats. Moreover, the plasma levels of triglycerides, total cholesterol, LDL-cholesterol, AST, ALT, LDH, andTNF-were also raised. The hepatic immunohistochemical analysis revealed a significant increase in the expression of inflammatory genes (COX-2, NF-B, and TNF-). Equally, it showed a rise of the apoptotic markers (a decrease in the expression of the Bcl-2 and an increase of the P53). In addition, the oral administration of oleuropein- and hydroxytyrosol-rich olive leaf extracts at 16 mg/kg similarly reduced the body weight and adipose tissue mass and improved the lipid profile. Moreover, these extracts, mainly the hydroxytyrosol-rich extract, reduced the elevated liver enzymes, enhanced the antioxidant status, and attenuated the liver inflammation and apoptosis. These findings suggest that the oleuropein- and hydroxytyrosol-rich olive leaf extracts possessed hypolipidemic and hepatoprotective effects against the HFD-induced metabolic disorders by enhancing the antioxidative defense system and blocking the expression of the proteins involved in inflammation and liver damage.

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PMID: 

FASEB J. 2020 Feb 6. Epub 2020 Feb 6. PMID: 32027412

Abstract Title: 

Hydroxytyrosol stimulates neurogenesis in aged dentate gyrus by enhancing stem and progenitor cell proliferation and neuron survival.

Abstract: 

The dentate gyrus of the hippocampus is one of two brain areas generating throughout life new neurons, which contribute to the formation of episodic/associative memories. During aging, the production of new neurons decreases and a cognitive decline occurs. Dietary factors influence neuronal function and synaptic plasticity; among them the phenolic compound hydroxytyrosol (HTyr), present in olive oil, displays neuroprotective effects. As age impacts primarily on the hippocampus-dependent cognitive processes, we wondered whether HTyr could stimulate hippocampal neurogenesis in vivo in adult and aged wild-type mice as well as in the B-cell translocation 1 gene (Btg1) knockout mouse model of accelerated neural aging. We found that treatment with HTyr activates neurogenesis in the dentate gyrus of adult, aged, and Btg1-null mice, by increasing survival of new neurons and decreasing apoptosis. Notably, however, in the aged and Btg1-null dentate gyrus, HTyr treatment also stimulates the proliferation of stem and progenitor cells, whereas in the adult dentate gyrus HTyr lacks any proliferative effect. Moreover, the new neurons generated in aged mice after HTyr treatment are recruited to existing circuits, as shown by the increase of BrdU/c-fosneurons. Finally, HTyr treatment also reduces the markers of aging lipofuscin and Iba1. Overall, our findings indicate that HTyr treatment counteracts neurogenesis decline during aging.

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PMID: 

Front Nutr. 2014 ;1:18. Epub 2014 Oct 27. PMID: 25988120

Abstract Title: 

Hydroxytyrosol and potential uses in cardiovascular diseases, cancer, and AIDS.

Abstract: 

Hydroxytyrosol is one of the main phenolic components of olive oil. It is present in the fruit and leaf of the olive (Olea europaea L.). During the past decades, it has been well documented that this phenolic compound has health benefits and a protective action has been found in preclinical studies against several diseases. Here, we review its bioavailability in human beings and several assays showing significant results related with cardiovascular diseases, cancer, and acquired immunodeficiency syndrome (AIDS). Mechanisms of action include potent anti-oxidant and anti-inflammatory effects, among others. The importance of hydroxytyrosol in protection of low-density lipoproteins and consequently its implication in the reduction of cardiovascular disease risk has been highlighted by the European Food Safety Authority, concluding that 5 mg of hydroxytyrosol and its derivatives should be consumed daily to reach this effect at physiological level. We discuss the potential uses of this compound in supplements, nutraceutic foods, or topical formulations in the disease risk reduction. Finally, we conclude that more studies are neededto sustain or reject many other health claims not yet fully documented and to validate these newly available hydroxytyrosol-based products, because it seems to be a good candidate to reduce the risk of diseases mentioned.

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PMID: 

BMC Complement Altern Med. 2019 Jun 21 ;19(1):145. Epub 2019 Jun 21. PMID: 31226983

Abstract Title: 

Antimicrobial activity of red wine and oenological extracts against periodontal pathogens in a validated oral biofilm model.

Abstract: 

BACKGROUND: Previous research findings support an antimicrobial effect of polyphenols against a variety of pathogens, but there is no evidence of this effect against periodontal pathogens in complex biofilms. The purpose of this study was to evaluate the antimicrobial activity of red wine and oenological extracts, rich in polyphenols, against the periodontal pathogens Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum and total bacteria growing in an in vitro oral biofilm static model.METHODS: A previously validated biofilm model, including Streptococcus oralis, Actinomyces naeslundii, Veillonella parvula, F. nucleatum, P. gingivalis and A. actinomycetemcomitans was developed on sterile hydroxyapatite discs. Red wine (and dealcoholized wine), and two polyphenols-rich extracts (from wine and grape seeds) were applied to 72 h biofilms by dipping the discs during 1 and 5 min in the wine solutions and during 30 s and 1 min in the oenological extracts. Resulting biofilms were analyzed by confocal laser scanning microscopy and viable bacteria (colony forming units/mL) were measured by quantitative polymerase chainreaction combined with propidium monoazide. A generalized linear model was constructed to determine the effect of the tested products on the viable bacterial counts of A. actinomycetemcomitans, P. gingivalis and F. nucleatum, as well on the total number of viable bacteria.RESULTS: The results showed that red wine and dealcoholized red wine caused reduction in viability of total bacteria within the biofilm, with statistically significant reductions in the number of viable P. gingivalis after 1 min (p = 0.008) and in A. actinomycetemcomitans after 5 min of exposure (p = 0.011) with red wine. No evidence of relevant antibacterial effect was observed with the oenological extracts, with statistically significant reductions of F. nucleatum after 30 s of exposure to both oenological extracts (p = 0.001).CONCLUSIONS: Although moderate, the antimicrobial impact observed in the total bacterial counts and counts of A. actinomycetemcomitans, P. gingivalis and F. nucleatum, encourage further investigations on the potential use of these natural products in the prevention and treatment of periodontal diseases.

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PMID: 

J Trace Elem Med Biol. 2020 Jan ;57:126407. Epub 2019 Sep 18. PMID: 31570250

Abstract Title: 

Protective effects of grape seed proanthocyanidins against iron overload-induced renal oxidative damage in rats.

Abstract: 

BACKGROUND: Excessive exposure to iron can cause kidney damage, and chelating drugs such as deferoxamine and deferiprone have limited usefulness in treating iron poisoning. This study was designed to investigate the protective effects of grape seed proanthocyanidins (GSPAs) against iron overload induced nephrotoxicity in rats. The roles of GSPAs in chelating iron, antioxidant activity, renal function, pathological section, and apoptosis-related gene expression were assessed.METHODS: Newly weaned male Sprague-Dawley rats aged 21 days (weight, 65 ± 5 g) were randomly divided into four groups containing 10 rats each: normal control (negative) group, iron overload (positive) group, GSPAs group, and GSPAs + iron overload (test) group. Iron dextran injections (2.5 mg⋅ kg) and GSPAs (25 mg⋅ kg) were intraperitoneally and intragastrically administered to rats daily for 7 weeks, respectively. Measurements included red blood cell (RBC) count and hemoglobin (Hb) level, serum total iron-binding capacity (TIBC), renal iron content, glutathione peroxidase (GSH-Px) activity, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, total antioxidant activity (T-AOC), creatinine (CR) and blood urea nitrogen (BUN) levels, pathological changes, and apoptotic Fas, Bax expressions in the kidney tissue. Differences among the dietary groups were determined using one-way analysis of variance with post-hoc Tukey's test. P

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PMID: 

Rom J Morphol Embryol. 2019 ;60(3):921-929. PMID: 31912105

Abstract Title: 

Red grape juice protects the rat thyroid gland against hypercholesterolemic changes. Ultrastructural and biochemical evidences.

Abstract: 

OBJECTIVES: This study aimed to assess the impact of high cholesterol diet (HCD)-induced hypercholesterolemia on the rat thyroid gland and investigate the role of grape juice (GJ) in reducing such impact through biochemical and histopathological methods.MATERIALS AND METHODS: Thirty male Wistar rats sorted into three groups (the control, HCD-fed group, and the HCD+GJ fed group for 13 weeks) were used in this study. Lipid profile, blood glucose and insulin, thyroid hormones, some oxidants/antioxidants parameters were assessed. After the end of the experiment, thyroid glands were dissected out and processed for histopathological assessment using the light and electron microscopy.RESULTS: Based on the lipid profile, HCD induced hypercholesterolemia in rats after 13 weeks. This resulted in significant (p

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PMID: 

Antioxidants (Basel). 2020 Jan 10 ;9(1). Epub 2020 Jan 10. PMID: 31936711

Abstract Title: 

Polyphenols from Food and Natural Products: Neuroprotection and Safety.

Abstract: 

Polyphenols are naturally occurring micronutrients that are present in many food sources. Besides being potent antioxidants, these molecules may also possess anti-inflammatory properties. Many studies have highlighted their potential role in the prevention and treatment of various pathological conditions connected to oxidative stress and inflammation (e.g., cancer, and cardiovascular and neurodegenerative disorders). Neurodegenerative diseases are globally one of the main causes of death and represent an enormous burden in terms of human suffering, social distress, and economic costs. Recent data expanded on the initial antioxidant-based mechanism of polyphenols' action by showing that they are also able to modulate several cell-signaling pathways and mediators. The proposed benefits of polyphenols, either as protective/prophylactic substances or as therapeutic molecules, may be achieved by the consumption of a natural polyphenol-enriched diet, by their use as food supplements, or with formulations as pharmaceutical drugs/nutraceuticals. It has also been proved that the health effects of polyphenols depend on the consumed amount and their bioavailability. However, their overconsumption may raise safety concerns due to the accumulation of high levels of these molecules in the organism, particularly if we consider the loose regulatory legislation regarding the commercialization and use of food supplements. This review addresses the main beneficial effects of food polyphenols, and focuses on neuroprotection and the safety issues related to overconsumption.

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PMID: 

Drug Discov Ther. 2019 ;13(6):335-342. PMID: 31956232

Abstract Title: 

Methanol extract of Lonicera caerulea var. emphyllocalyx fruit has anti-motility and anti-biofilm activity against enteropathogenic Escherichia coli.

Abstract: 

Foodborne diseases have become a worldwide problem that threatens public health and welfare. Enteropathogenic Escherichia coli (EPEC) is one of major pathogens of moderate to severe diarrhea. The increased prevalence of EPEC strains that produce extended spectrumβ-lactamase (ESBL) has deepened the problem. The fruit of Lonicera caerulea var. emphyllocalyx (LCE) has been used as a traditional food preservative and medicine in northern temperate zones such as Hokkaido Island, Japan. In this study, we investigated the antibacterial effect of LCE fruit extract(LCEE) against EPEC. The antibacterial activities of LCEE were examined by bacterial growth, time-kill curve, soft-agar motility, electron microscopy, and 96 well-microplate biofilm assays. We also investigated the bacterial mRNA expression of biofilm-associated genes (fliC, csgA, and fimA) by quantitative real-time PCR assays. LCEE was found to suppress the growth, time-kill curve, and spread of EPEC. It also reduced the biofilm formation in a dose-dependent manner. Morphological analysis using transmission and scanning electron microscopy revealed that LCEE diminished the function of flagella resulting in reduced motility and biofilm formation. The mRNA expression of all three biofilm associated genes was downregulated under LCEE treatment. Extracts of the fruit of LCE inhibit the motility and biofilm formation of EPEC as a result of the inhibition of flagella development and function. We propose LCEE as a therapeutic candidate for the effective therapy of EPEC-associated infectious diseases.

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PMID: 

Front Pharmacol. 2018 ;9:1413. Epub 2018 Nov 30. PMID: 30555330

Abstract Title: 

β-Elemene Synergizes With Gefitinib to Inhibit Stem-Like Phenotypes and Progression of Lung Cancer via Down-Regulating EZH2.

Abstract: 

The inhibitors for EGF receptor tyrosine kinase (EGFR-TKIs) such as gefitinib have been used as a standard treatment for non-small cell lung cancer (NSCLC), but the increasingly occurrence of drug resistance, the associated adverse effects and the enrichment of cancer stem cells significantly impedes its clinical application.β-elemene is a natural sesquiterpene with potent anti-cancer ability, and also it is renowned for its plant-origin, safety and the additive effect with traditional therapies, which prompt us to explore its potential to co-operate with TKIs to achieve greater therapeutic efficacy. Impressively, ourstudy demonstrates that, elemene, in combination of gefitinib, displayed a significantly higher activity in inhibiting lung cancer cellular proliferation, migration and invasion. More importantly, combinative treatment profoundly impaired the epithelial to mesenchymal transition (EMT), the stem-likeproperties and the self-renewal capacity of lung cancer cells, and hence impeded thetumor development. We also reveal that the synergistic anti-tumor effect of elemene and gefitinib was largely mediated their regulation of enhancer of zeste homolog 2 (EZH2), an oncogenic histone methyltransferase and gene transcriptional regulator. Thus, our data indicate that combinative treatment of elemene and gefitinib has greater anti-neoplastic activity and greater efficacies in targeting cancer stem-like properties, mainly through regulating the malignant gene modifier and hence the subsequent effector molecules required for cancer progression. The findings may have potential implications for treating aggressive and resistant lung cancers.

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PMID: 

Biomed Pharmacother. 2019 Jun ;114:108812. Epub 2019 Apr 6. PMID: 30965237

Abstract Title: 

Molecular targets ofβ-elemene, a herbal extract used in traditional Chinese medicine, and its potential role in cancer therapy: A review.

Abstract: 

β-Elemene is a sesquiterpene compound extracted from the herb Curcuma Rhizoma and is used in traditional Chinese medicine (TCM) to treat several types of cancer, with no reported severe adverse effects. Recent studies, using in vitro and in vivo studies combined with molecular methods, have shown that β-elemene can inhibit cell proliferation, arrest the cell cycle, and induce cell apoptosis. Recent studies have identified the molecular targets of β-elemene that may have a role in cancer therapy. This review aims to discuss the anticancer potential of β-elemene through its actions on several molecular targets including kinase enzymes, transcription factors, growth factors and their receptors, and proteins. β-Elemene also regulates the expression of several key molecules that are involved in tumor angiogenesis and metastasis including vascular endothelial growth factor (VEGF), matrixmetalloproteinases (MMPs), E-cadherin, N-cadherin, and vimentin. Also, β-elemene has been shown to have regulatory effects on the immune response and increases the sensitivity of cancer cells to chemoradiotherapy and has shown effects on multidrug resistance (MDR) in malignancy. Recent studies haveshown that β-elemene can induce autophagy, which prevents cancer cells from undergoing apoptosis. Therefore, the molecular mechanisms for the treatment effects on cancer of the herbal extract, β-elemene, which has been used for centuries in traditional Chinese medicine, are now being studied andidentified.

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