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Bioavailability and bioactivity of free ellagic acid compared to pomegranate juice.
Long, J, Guo, Y, Yang, J, Henning, SM, Lee, RP, Rasmussen, A, Zhang, L, Lu, QY, Heber, D, Li, Z
Food & function. 2019;(10):6582-6588
Abstract
Pomegranates are an excellent source of ellagic acid (EA), ellagitannins (ETs), anthocyanins and other phytochemicals. The health benefits of pomegranate (Pom) have been mainly related to its EA and ET content. The objective of the present study was to determine EA bioavailability and bioactivity from different sources such as pure/free or natural form (PomJ). This was a cross-over study with healthy volunteers consuming one dose of EA dietary supplement (500 mg free EA) vs. one serving of PomJ (237 mL, ∼120 mg of EA) in a random order. Our data showed that there was no difference in plasma EA concentration between PomJ and EA intake; however, urinary dimethylellagic acid glucuronide (DMEAG), normalized to creatinine, was significantly higher after the consumption of PomJ compared to EA. Plasma insulin at 1 h increased after PomJ consumption compared to the baseline while decreased after EA consumption compared to the baseline. Plasma glucose decreased below the baseline 2 h after the consumption of PomJ but not EA. Plasma leptin was significantly decreased at 1 and 2 h after PomJ and EA consumption. Plasma MCP1 decreased only after PomJ but not after pure EA consumption. To conclude, one serving of PomJ provided the same level of EA in blood, while the increase in phase II metabolism of EA and an acute suppression of plasma MCP1 were only observed after PomJ consumption, suggesting that other constituents present in PomJ, in addition to EA, are bioactive and likely play a role in regulating EA phase II metabolism.
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A Pilot Study of a Grape Seed Procyanidin Extract for Lung Cancer Chemoprevention.
Mao, JT, Lu, QY, Xue, B, Neis, P, Zamora, FD, Lundmark, L, Qualls, C, Massie, L
Cancer prevention research (Philadelphia, Pa.). 2019;(8):557-566
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Abstract
Grape seed procyanidin extract (GSE) had been reported to exert antineoplastic properties in preclinical studies. A modified phase I, open-label, dose-escalation clinical study was conducted to evaluate the safety, tolerability, MTD, and potential chemopreventive effects of leucoselect phytosome (LP), a standardized GSE complexed with soy phospholipids to enhance bioavailability, in heavy active and former smokers. Eight subjects ages 46-68 years were enrolled into the study and treated with escalating oral doses of LP for 3 months. Bronchoscopies with bronchoalveolar lavage and bronchial biopsies were performed before and after 3 months of LP treatment. Hematoxylin and eosin stain for histopathology grading and IHC examination for Ki-67 proliferative labeling index (Ki-67 LI) were carried out on serially matched bronchial biopsy samples from each subject to determine responses to treatment. Two subjects were withdrawn due to issues unrelated to the study medication, and a total of 6 subjects completed the full study course. In general, 3 months of LP, reaching the highest dose per study protocol was well tolerated and no dosing adjustment was necessary. Such a treatment regimen significantly decreased bronchial Ki-67 LI by an average of 55% (P = 0.041), with concomitant decreases in serum miR-19a, -19b, and -106b, which were oncomirs previously reported to be downregulated by GSE, including LP, in preclinical studies. In spite of not reaching the original enrollment goal of 20, our findings nonetheless support the continued clinical translation of GSE as an antineoplastic and chemopreventive agent against lung cancer.
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Grape Seed Procyanidin Extract Mediates Antineoplastic Effects against Lung Cancer via Modulations of Prostacyclin and 15-HETE Eicosanoid Pathways.
Mao, JT, Smoake, J, Park, HK, Lu, QY, Xue, B
Cancer prevention research (Philadelphia, Pa.). 2016;(12):925-932
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Abstract
Grape seed procyanidin extract (GSE) has been reported to exert antineoplastic properties via the inhibition of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) eicosanoid pathways. In addition, ample data link carcinogenesis to inflammatory events involving other major eicosanoid metabolic pathways, including prostacyclin (PGI2) and 15-hydroxyeicosatetraenoic acid (15-HETE). We therefore evaluated the effects of GSE on prostacyclin synthase (PTGIS)/PGI2 and 15-lipoxigenase-2 (15-LOX-2)/15-HETE productions by human lung premalignant and malignant cells and correlated the findings with antiproliferative or proapoptotic effects of GSE. The effects of GSE on PGI2 and 15-HETE productions by human bronchoalveolar lavage (BAL) cells ex vivo were also determined. We further evaluated the bioactivity of oral administration of leucoselect phytosome (a standardized GSE) in the lungs of subjects participating in a lung cancer chemoprevention trial, by comparing the antiproliferative effects of coculturing matched pre- versus posttreatment BAL fluids with lung premalignant and malignant cells. GSE significantly increased PGI2 (as measured by 6-keto PGF1α) and 15-HETE productions by these cells. Transfections of PTGIS or 15-LOX-2-specific siRNA partially abrogated the antiproliferative or proapoptotic effects of GSE in lung premalignant and malignant cells, respectively. GSE also increased PTGIS and inhibition of caspase-3, and transfection of 15-LOX-2 siRNA abrogated the GSE-induced apoptosis in A549 cells. In addition, culture supernatants from ex vivo GSE-treated baseline BAL cells, as well as BAL fluids from subjects treated with leucoselect phytosome, significantly decreased proliferations of lung premalignant and malignant cells. Our findings support the continued investigation of GSE as an anti-neoplastic and chemopreventive agent against lung cancer. Cancer Prev Res; 9(12); 925-32. ©2016 AACR.
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Comparison of effects of 18F-FDG PET-CT and MRI in identifying and grading gliomas.
Song, PJ, Lu, QY, Li, MY, Li, X, Shen, F
Journal of biological regulators and homeostatic agents. 2016;(3):833-838
Abstract
Glioma is the most common type of brain tumor. Malignant gliomas tend to have an increasingly higher incidence and are difficult to treat. Therefore, an accurate diagnosis of the grade of glioma before surgery is very important for planning surgery and determining prognosis. To compare the values of 18F-deoxyglucose positron emission tomography/computer tomography (18F-FDG PET-CT) and magnetic resonance imaging (MRI) for identifying and grading gliomas, we selected 70 patients who were diagnosed as having a primary glioma or suspected glioma at the Peoples Hospital of Liaocheng in Shandong, China, and divided them into an observation group, which was examined by 18F-FDG PET-CT and a control group, which was examined by MRI. Image analysis, visual semi-quantitative analysis and qualitative analysis, follow-up and pathological results of the two groups were compared. Specificity, accuracy and sensitivity of brain MRI and PET-CT in grading the gliomas were calculated, and the results obtained were processed by Chi-squared test. Standard uptake value (SUV), SUVcorrect and L/WM (SUVmax ratio of a lesion to normal white matters in the opposite side) of FDG in the different grades of glioma were analyzed by single-factor variance analysis. Postoperative pathological detection confirmed 47 cases of glioma; the sensitivity, specificity and accuracy of PET-CT in grading glioma were all higher than those of MRI (P less than 0.05); the correlation between SUV and glioma grade, between SUVcorrect and glioma grade, and between L/WM and glioma had significant difference (P less than 0.05). Thus, it was concluded that 18F-FDG PET-CT performs better in diagnosing gliomas than MRI and is also more suitable for identifying different grades of glioma.
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Pomegranate extract induces ellagitannin metabolite formation and changes stool microbiota in healthy volunteers.
Li, Z, Henning, SM, Lee, RP, Lu, QY, Summanen, PH, Thames, G, Corbett, K, Downes, J, Tseng, CH, Finegold, SM, et al
Food & function. 2015;(8):2487-95
Abstract
The health benefits of pomegranate (POM) consumption are attributed to ellagitannins and their metabolites, formed and absorbed in the intestine by the microbiota. In this study twenty healthy participants consumed 1000 mg of POM extract daily for four weeks. Based on urinary and fecal content of the POM metabolite urolithin A (UA), we observed three distinct groups: (1) individuals with no baseline UA presence but induction of UA formation by POM extract consumption (n = 9); (2) baseline UA formation which was enhanced by POM extract consumption (N = 5) and (3) no baseline UA production, which was not inducible (N = 6). Compared to baseline the phylum Actinobacteria was increased and Firmicutes decreased significantly in individuals forming UA (producers). Verrucomicrobia (Akkermansia muciniphila) was 33 and 47-fold higher in stool samples of UA producers compared to non-producers at baseline and after 4 weeks, respectively. In UA producers, the genera Butyrivibrio, Enterobacter, Escherichia, Lactobacillus, Prevotella, Serratia and Veillonella were increased and Collinsella decreased significantly at week 4 compared to baseline. The consumption of pomegranate resulted in the formation of its metabolites in some but not all participants. POM extract consumption may induce health benefits secondary to changes in the microbiota.
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Raw garlic consumption as a protective factor for lung cancer, a population-based case-control study in a Chinese population.
Jin, ZY, Wu, M, Han, RQ, Zhang, XF, Wang, XS, Liu, AM, Zhou, JY, Lu, QY, Zhang, ZF, Zhao, JK
Cancer prevention research (Philadelphia, Pa.). 2013;(7):711-8
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Abstract
Protective effect of garlic on the development of cancer has been reported in the in vitro and in vivo experimental studies; however, few human epidemiologic studies have evaluated the relationship. A population-based case-control study has been conducted in a Chinese population from 2003 to 2010, with the aim to explore the association between raw garlic consumption and lung cancer. Epidemiologic data were collected by face-to-face interviews using a standard questionnaire among 1,424 lung cancer cases and 4,543 healthy controls. Unconditional logistic regression was used to estimate adjusted ORs and their 95% confidence intervals (CI), and to evaluate ratio of ORs (ROR) for multiplicative interactions between raw garlic consumption and other risk factors. After adjusting for potential confounding factors, raw garlic consumption of 2 times or more per week is inversely associated with lung cancer (OR = 0.56; 95% CI, 0.44-0.72) with a monotonic dose-response relationship (Ptrend < 0.001). Furthermore, strong interactions at either additive and/or multiplicative scales were observed between raw garlic consumption and tobacco smoking [synergy index (SI) = 0.70; 95% CI, 0.57-0.85; and ROR = 0.78; 95% CI, 0.67-0.90], as well as high-temperature cooking oil fume (ROR = 0.77; 95% CI, 0.59-1.00). In conclusion, protective association between intake of raw garlic and lung cancer has been observed with a dose-response pattern, suggesting that garlic may potentially serve as a chemopreventive agent for lung cancer. Effective components in garlic in lung cancer chemoprevention warrant further in-depth investigation.