PMID: 

Chem Biol Interact. 2019 Sep 1 ;310:108740. Epub 2019 Jul 6. PMID: 31288002

Abstract Title: 

Luteolin and 5-flurouracil act synergistically to induce cellular weapons in experimentally induced Solid Ehrlich Carcinoma: Realistic role of P53; a guardian fights in a cellular battle.

Abstract: 

BACKGROUND: Solid Ehrlich Carcinoma (SEC) is an undifferentiated tumor used in tumor studies and chemotherapy investigations.AIM: to assess the anti-tumor potential of luteolin when used either alone or combined to 5-fluorouracil (5-FU) against SEC.METHOD: SEC was induced in 40 female mice; they were categorized into 4 equal groups; group I (untreated SEC), group II (5-FU treated SEC), group III (luteolin treated SEC) and group IV (5-FU + luteolin treated SEC). Tumor volume and weight were calculated. P53, p21, caspase 3 and damage regulated autophagy modulator (DRAM) were assessed. Biomarkers of oxidant/antioxidant status in addition to immunohistochemistry for cylin D1 were evaluated.RESULTS: combined administration of luteolin and 5-FU in SEC model increased levels of p53, p21, caspase 3, DRAM and survivability while, tumor volume, weight, thioredoxin reductase one (TR1) activity and cyclin D1 expression showed the reverse with restoration of oxidant/antioxidant indices.CONCLUSION: current results proved the antitumor therapeutic effects of luteolin alone or combined with 5-FU as a novel strategy for cancer therapy.

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PMID: 

J Nutr Biochem. 2019 Sep ;71:72-81. Epub 2019 Jun 20. PMID: 31302373

Abstract Title: 

Luteolin reduces adipose tissue macrophage inflammation and insulin resistance in postmenopausal obese mice.

Abstract: 

Previously, we showed that loss of ovarian function in mice fed high-fat diet exacerbated insulin resistance and adipose tissue inflammation. In the current study, we tested whether consumption of luteolin, an anti-inflammatory flavonoid, could mitigate adipose tissue inflammation and insulin resistance in obese ovariectomized mice. Nine-week-old ovariectomized C57BL/6 mice were fed a low-fat diet, high-fat diet (HFD) or HFD supplemented with 0.005% luteolin (HFD+L) for 16 weeks. Results showed no difference in body weight or fat mass between mice fed HFD+L and those fed HFD. However, luteolin supplementation resulted in lower CD11cmacrophages in gonadal adipose tissue, as well as a trend toward lower macrophage infiltration. Luteolin supplementation also significantly lowered mRNA expression of inflammatory and M1 markers MCP-1, CD11c, TNF-α and IL-6, while maintaining expression of M2 marker MGL1. Consistent with this, the in vitro luteolin treatment, with or without the presence of estrogen, inhibited lipopolysaccharide-induced polarization of RAW 264.7 cells toward M1 phenotype. We further found that luteolin supplementation protected mice from insulin resistance induced by HFD consumption; this improved insulin resistance was correlated with reductions in CD11cadipose tissue macrophages. Taken together, these findings indicate that dietary luteolin supplementation attenuates adipose tissue inflammation and insulin resistance found in mice with loss of ovarian function coupled with an HFD intake, and this effect may be partly mediated through suppressing M1-like polarization of macrophages in adipose tissue. These results have clinical implication in implementing dietary intervention for prevention of metabolic syndrome associated with postmenopause and obesity.

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PMID: 

Toxicol In Vitro. 2019 Aug 13 ;61:104624. Epub 2019 Aug 13. PMID: 31419504

Abstract Title: 

PTP1B phosphatase as a novel target of oleuropein activity in MCF-7 breast cancer model.

Abstract: 

Phosphatase PTP1B has become a therapeutic target for the treatment of type 2-diabetes, whereas recent studies have revealed that PTP1B plays a pivotal role in pathophysiology and development of breast cancer. Oleuropein is a natural, phenolic compound with anticancer activity. The aim of this study was to address the question whether PTP1B constitutes a target for oleuropein in breast cancer MCF-7 cells. The cellular MCF-7 breast cancer model was used in the study. The experiments were performed using cellular viability tests, Elisa assays, immunoprecipitation, flow cytometry analyses and computer modelling. Herein, we evidenced that the reduced activity of phosphatase PTP1B after treatment with oleuropein is strictly correlated with decreased MCF-7 cellular viability and cell cycle arrest. These results provide new insight into further research on oleuropein and possible role of the compound in adjuvant treatment of breast cancer.

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PMID: 

Oxid Med Cell Longev. 2019 ;2019:8576961. Epub 2019 Jul 22. PMID: 31428230

Abstract Title: 

Oleuropein-Induced Apoptosis Is Mediated by Mitochondrial Glyoxalase 2 in NSCLC A549 Cells: A Mechanistic Inside and a Possible Novel Nonenzymatic Role for an Ancient Enzyme.

Abstract: 

Oleuropein (OP) is a bioactive compound derived from plants of the genus Oleaceae exhibiting antitumor properties in several human cancers, including non-small-cell lung cancer (NSCLC). Recent evidence suggests that OP has proapoptotic effects on NSCLC cells via the mitochondrial apoptotic pathway. However, the exact molecular mechanisms behind the apoptogenic action of OP in NSCLC are still largely unknown. Glyoxalase 2 (Glo2) is an ancient enzyme belonging to the glyoxalase system involved in the detoxification of glycolysis-derived methylglyoxal. However, emerging evidence suggests that Glo2 may have also nonenzymatic roles in some malignant cells. In the present study, we evaluated whether and how Glo2 participated in the proapoptotic effects of OP in NSCLC A549 cells. Our results indicate that OP is able to induce apoptosis in A549 cells through the upregulation of mitochondrial Glo2 (mGlo2), mediated by the superoxide anion and Akt signaling pathway. Moreover, our data shows that the proapoptotic role of mGlo2, observed following OP exposure, occurs via the interaction of mGlo2 with the proapoptotic Bax protein. Conversely, OP does not alter the behavior of nonmalignant human BEAS-2B cells or mGlo2 expression, thus suggesting a specific anticancer role for this bioactive compound in NSCLC. Our data identify a novel pathway through which OP exerts a proapoptotic effect in NSCLC and suggest, for the first time, a novel, nonenzymatic antiapoptotic role for this ancient enzyme in NSCLC.

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PMID: 

Int J Clin Pediatr Dent. 2019 Mar-Apr;12(2):133-138. PMID: 31571786

Abstract Title: 

Effect of Green Tea Extract Mouthwash on SalivaryCounts in a Group of Preschool Children: AnStudy.

Abstract: 

Aim: This study was conducted to evaluate the effectiveness of green tea mouthwash on the salivary level ofin the preschool children.Materials and methods: In this randomized controlled clinical trial, 40 cooperative children (4-5 years old) were divided into two groups. The study group included 20 children who did the routine tooth brushing 3 times/day, and then green tea extract mouthwash (8 mL/day) 2 times/day for 4 weeks. The control group included other 20 children who did the routine tooth brushing as the study group but did not use any green tea extract mouthwash. The quantitative microbiological laboratory cultivation method ofwas carried out for each child at the baseline, after 2 weeks, and after 4 weeks of the study period.Results: Statistically, the results showed that there was a statistically significant difference in the mean logcounts between the study and control groups in both follow-up periods after 2 weeks and after 4 weeks. Also, there were statistically significant mean percentage decreases in logcounts for the two groups.Conclusion: The use of green tea mouthwash showed promising results in reducing the cariogenic salivarycounts.Clinical significance: Green tea extract mouthwash is a nontoxic and safe, particularly for children. Catechins, the main bioactive ingredient of green tea, show an antibacterial action; thus, it has a promising effect in decreasing the count of salivaryand in the prevention of dental caries.How to cite this article: Salama MT, Alsughier ZA. Effect of Green Tea Extract Mouthwash on SalivaryCounts in a Group of Preschool Children: AnStudy. Int J Clin Pediatr Dent 2019;12(2):133-138.

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PMID: 

Mol Nutr Food Res. 2019 Oct 1:e1900811. Epub 2019 Oct 1. PMID: 31574193

Abstract Title: 

Green Tea Extract Treatment in Obese Mice with Nonalcoholic Steatohepatitis Restores the Hepatic Metabolome in Association with Limiting Endotoxemia-TLR4-NFκB-Mediated Inflammation.

Abstract: 

SCOPE: Catechin-rich green tea extract (GTE) alleviates nonalcoholic steatohepatitis (NASH) by lowering endotoxin-TLR4 (Toll-like receptor-4)-NFκB (nuclear factor kappa-B) inflammation. This study aimed to define altered MS-metabolomic responses during high-fat (HF)-induced NASH that are restored by GTE utilizing livers from an earlier study in which GTE decreased endotoxin-TLR4-NFκB liver injury.METHODS AND RESULTS: Mice are fed a low-fat (LF) or HF diet for 12 weeks and then randomized to LF or HF diets containing 0% or 2% GTE for an additional 8 weeks. Global MS-based metabolomics and targeted metabolite profiling of catechins/catechin metabolites are evaluated. GTE in HF mice restores hepatic metabolites implicated in dyslipidemia insulin resistance, and inflammation. These include 122 metabolites: amino acids, lipids, nucleotides, vitamins, bile acids, flavonoids, xenobiotics, and carbohydrates. Hepatic amino acids, B-vitamins, and bile acids are inversely correlated with biomarkers of insulin resistance, liver injury, steatosis, and inflammation. Further, phosphatidylcholine metabolites are positively correlated with biomarkers of liver injury and NFκB inflammation. Thirteen catechin metabolites are identified in livers of GTE-treated mice, mostly as phase II conjugates of parental catechins or microbial-derived valerolactones.CONCLUSION: The defined anti-inflammatory/metabolic interactions advance an understanding of the mechanism by which GTE catechins protect against NFκB-mediated liver injury in NASH.

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PMID: 

Arch Ital Urol Androl. 2019 Oct 2 ;91(3). Epub 2019 Oct 2. PMID: 31577096

Abstract Title: 

Green tea catechins for chemoprevention of prostate cancer in patients with histologically-proven HG-PIN or ASAP. Concise review and meta-analysis.

Abstract: 

A focused, single outcome meta-analysis on the protective role of extracts of green tea catechins against prostate cancer. Randomized, placebo-controlled studies enrolling patients with a histologically confirmed diagnosis of high-grade Prostate Intraepithelial Neoplasia or Atypical Small Acinar proliferation but no prostate cancer were included. Meta-analysis for binary data was performed using Mantel-Haenszel statistics, using a random-effects model. Heterogeneity was investigated by calculating the I2. Four studies matched the inclusion criteria for the review. The pooled population was 223 patients; 114 and 109 patients were randomized to catechin and placebo groups, respectively. Nine cases of prstate cancer occurred in the catechin arm (7.9%), and 24 cases were reported in the placebo arm (22%). Pooled analysis resulted in a significant reduction of cancer risk in favor of the catechin arm (risk-ratio = 0.41; 95% CI: 0.19- 0.86; I2 = 0). In conclusion, our data suggest that the intake of concentrated green tea catechin preparations may confer a significant protective effect to carriers of early neoplastic lesions in the prostate. The quality of the evidence is moderate, and additional, largescale studies are warranted to substantiate these preliminary findings.

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PMID: 

Nutr Res Pract. 2019 Oct ;13(5):393-398. Epub 2019 Jul 26. PMID: 31583058

Abstract Title: 

Tea consumption is associated with a reduced risk of coronary heart disease in female but not male populations in Guangzhou, China.

Abstract: 

BACKGROUND/OBJECTIVES: The association between tea consumption and risk of coronary heart disease (CHD) remains controversial. This study aimed to determine whether tea consumption has an effect on CHD risk in Chinese adults.SUBJECTS/METHODS: In this hospital-based case-control study, 267 cases of CHD and 235 non-CHD controls were enrolled. Blood samples from all cases were examined. Cardiac function indices (left ventricular ejection fraction, left ventricular end-diastolic dimension, lactate dehydrogenase, and creatine kinase of the muscle or brain type), blood lipid index (high-density lipoprotein cholesterol), and blood coagulation function indices (fibrinogen and activated partial thromboplastin time) were recorded. Tea consumption of study participants was assessed by a specifically designed questionnaire. The baseline characteristics of the study populations were recorded, and CHD-related biomarkers were detected. Differences in baseline characteristics of the study participants were examined using t-tests for continuous variables and chi-squared tests for categorical variables. Unconditional logistic regression was used to measure the association between tea and CHD.RESULTS: There were significant differences in cardiac function indices, blood lipid index, and blood coagulation indices between CHD cases and controls (6 days/week was beneficial for CHD prevention (adjusted OR = 0.183, 95% CI: 0.049-0.679,= 0.0112). When analyzed according to the duration of tea consumption, the risk of CHD was reduced in participants who had been drinking tea for 10-20 years (adjusted OR = 0.360, 95% CI: 0.137-0.946,= 0.0382).CONCLUSIONS: Tea consumption is associated with a reduced risk of CHD in female but not male populations in Guangzhou.

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PMID: 

Phytother Res. 2019 Apr ;33(4):901-909. Epub 2019 Feb 3. PMID: 30714232

Abstract Title: 

The nitrergic neurotransmission contributes to the anxiolytic-like effect of Citrus sinensis essential oil in animal models.

Abstract: 

Citrus fragrances have been used in aromatherapy for the treatment of anxiety, and the essential oil of Citrus sinensis (sweet orange) has shown promising results, although its mechanism of action was not known. The objective of this study was to evaluate the involvement of nitric oxide (NO) neurotransmission in the anxiolytic-like effect of C. sinensis essential oil. Swiss male mice were submitted to 15 min of C. sinensis essential oil inhalation (1%, 2.5%, 5%, and 10%) and tested in the marble-burying test, neophobia-induced hypophagia, and light/dark test. Locomotor activity was evaluated in an automated locomotor activity box. Thecoadministration of C. sinensis essential oil with L-arginine (200 mg/kg, i.p.), an NO precursor, was used for the behavioral evaluation of nitrergic system mediation. Additionally, the NO synthase activity was measured by nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) analysis in the cerebral cortex. C. sinensis essential oil exerted anxiolytic-like effect at dose that did not change locomotor activity. Moreover, L-arginine pretreatment prevented this anxiolytic-like effect on marble-burying test. Finally, C. sinensis essential oil reduced the NADPH-d positive cells. Thus, the nitrergic neurotransmission plays a relevant role in the anxiolytic-like effect C. sinensis essential oil.

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PMID: 

Nutr Neurosci. 2019 Oct 11:1-15. Epub 2019 Oct 11. PMID: 31603034

Abstract Title: 

Flavanol-rich lychee fruit extract substantially reduces progressive cognitive and molecular deficits in a triple-transgenic animal model of Alzheimer disease.

Abstract: 

Effective treatment to prevent or arrest the advance of Alzheimer disease (AD) has yet to be discovered. We investigated whether Oligonol, an FDA-approved flavanol-rich extract prepared from lychee fruit and green tea, exerted beneficial effects relevant to AD in a triple transgenic male mouse model of AD (3×Tg-AD). At 9 months of age, untreated 3×Tg-AD mice vs. wild-type (WT) controls displayed cognitive deficits in behavioral assays and, at 12 months, elevated levels of hippocampal amyloid beta-protein (Aβ), amyloid precursor protein (APP), tau phosphorylation, and pro-inflammatory cytokines. 3×Tg-AD mice given Oligonol showed fewer cognitive deficits and attenuated pathological indices at 12 months. Oligonol treatment of 3×Tg-AD mice modulated expression of some critical brain proteins that involve multiple pathways relevant to mitochondrial dysfunction, proteasomal failure, endoplasmic reticulum (ER) stress and synaptic impairment. Together, these results demonstrate that continuous Oligonol treatment attenuates AD-like pathology and cognitive impairment of 3×Tg-AD mice and set the stage for clinical trials of this flavanol-rich plant extract in patients with early AD.

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