Article

Inhibition of Angiotensin Converting Enzyme Activity by Flavanol-Rich Foods

February 2006
Journal of Agricultural and Food Chemistry 54(1):229-34

February 2006
54(1):229-34

DOI:10.1021/jf052263o

Source
PubMed

Authors:

Lucas Actis-Goretta

Nestlé S.A.

Cesar Fraga

Universidad de Buenos Aires

Angiotensin converting enzyme (ACE) activity was evaluated in the presence of flavanol-rich foods, i.e., wines, chocolates, and teas, and of purified flavonoids. All foods assayed inhibited ACE activity, red wines being more effective than white wine, and green tea more effective than black tea. The inhibition of ACE activity was associated with both phenolic and flavanol content in the foods. When isolated polyphenols were assayed, procyanidins (dimer and hexamer) and epigallocatechin significantly inhibited enzyme activity; similar concentrations of (+)-catechin, (-)-epicatechin, gallic acid, chlorogenic acid, caffeic acid, quercetin, kaempferol, and resveratrol were ineffective. When ACE activity was assayed in rat kidney membranes in the presence of chocolate extracts or purified procyanidins, it was observed that the inhibition depended on the chocolate content of flavanols and the number of flavanol units constituting the procyanidin. These experiments demonstrate that flavanols either isolated or present in foods could inhibit ACE activity. The occurrence of such inhibition in vivo needs to be determined, although is supported by the association between the consumption of flavanol-rich foods and reductions in blood pressure observed in several experimental models.

Identification and Molecular Docking Analysis of Angiotensin-Converting Enzyme Inhibitors from Finger Millet (Eleusine coracana)

Article

Full-text available

May 2024
PLANT FOOD HUM NUTR

Hypertension remains a significant global health concern, contributing significantly to cardiovascular diseases and mortality rates. The inhibition of angiotensin-converting enzyme (ACE) plays a crucial role in alleviating high blood pressure. We investigated the potential of finger millets (Eleusine coracana) as a natural remedy for hypertension by isolating and characterizing its ACE-inhibitory compound. First, we evaluated the ACE-inhibitory activity of the finger millet ethanol extract and subsequently proceeded with solvent fractionation. Among the solvent fractions, the ethyl acetate fraction exhibited the highest ACE inhibitory activity and was further fractionated. Using preparative high-performance liquid chromatography, the ethyl acetate fraction was separated into four subfractions, with fraction 2 (F2) exhibiting the highest ACE inhibitory activity. Subsequent 1 H-nuclear magnetic resonance (NMR) and 13 C-NMR analyses confirmed that the isolated compound from F2 was catechin. Furthermore, molecular docking studies indicated that catechin has the potential to act as an ACE inhibitor. These findings suggest that finger millets, particularly as a source of catechin, have the potential to be used as a natural antihypertensive.

Regular Consumption of Cocoa and Red Berries as a Strategy to Improve Cardiovascular Biomarkers via Modulation of Microbiota Metabolism in Healthy Aging Adults

Article

Full-text available

May 2023

The aim of the present study was to analyze the effects of cocoa flavanols and red berry anthocyanins on cardiovascular biomarkers, such as homocysteine, angiotensin-converting enzyme (ACE), nitric oxide (NO), flow-mediated vasodilation (FMD), blood pressure and lipid profile. Additionally, we aimed to ascertain their possible interactions with microbiota related metabolites, such as secondary bile acids (SBA), short-chain fatty acids (SCFA) and trimethylamine N-oxide (TMAO). A randomized, parallel-group study, single-blind for the research team, was performed on 60 healthy volunteers between the ages of 45 and 85, who consumed 2.5 g/day of cocoa powder (9.59 mg/day of total flavanols), 5 g/day of a red berry mixture (13.9 mg/day of total anthocyanins) or 7.5 g/day of a combination of both for 12 weeks. The group that had consumed cocoa showed a significant reduction in TMAO (p = 0.03) and uric acid (p = 0.01) levels in serum, accompanied by an increase in FMD values (p = 0.03) and total polyphenols. corrected by creatinine (p = 0.03) after the intervention. These latter values negatively correlated with the TMAO concentration (R = −0.57, p = 0.02). Additionally, we observed an increase in carbohydrate fermentation in the groups that had consumed cocoa (p = 0.04) and red berries (p = 0.04) between the beginning and the end of the intervention. This increase in carbohydrate fermentation was correlated with lower levels of TC/HDL ratio (p = 0.01), systolic (p = 0.01) and diastolic blood pressure (p = 0.01). In conclusion, our study showed a positive modulation of microbiota metabolism after a regular intake of cocoa flavanols and red berry anthocyanins that led to an improvement in cardiovascular function, especially in the group that consumed cocoa.

Bioavailability of Citrus Flavanones and Their Effect on Cardiovascular Health Biomarkers

Thesis

Full-text available

Jul 2015

Abdurrahman Sweidan

Consumption of flavanones has been associated with a reduction in risk of developing CVD, however flavanone bioavailability varies greatly in the population. The thesis aim was to investigate variations in absorption, as assessed by urinary excretion and, for the first time, the effect of commercially-available citrus supplements on CVD risk biomarkers. In study 1, 15 participants consumed orange juice (OJ; 500 ml: 8 mg naringenin, 42 mg hesperidin/100 ml) and/or soya-nuts (25g): 30 mg daidzein, 57 mg genistein/100 g). Urine was collected at 0, 0-4, 4-8, 8-12, 12-24 and 24-36 hr on each of three separate occasions; saliva was collected hourly (0-8 and 24 hr) after co-ingestion of OJ and soya�nuts. Daidzein was excreted to a greater extent than genistein (27-28% of dose ingested compared to 16-19%), whilst naringenin was excreted to a greater extent than hesperetin (9% vs 2.5-3%). There was a strong positive correlation between excretion of daidzein and genistein (r=0.72, p<0.01), and for hesperetin and naringenin (r=0.72, p< 0.01). Moreover, the amount of naringenin, and daidzein or genistein were correlated when co�ingested (r=0.73, p<0.01; r=0.49, p=0.05). No flavonoid was detected in saliva at any time point. In study 2, 23 overweight participants ingested citrus supplements (114 mg hesperidin) or a placebo daily for 28 days in a randomised, cross-over intervention. Urinary excretion (24 hr) was analysed by LC-MS to determine flavanone metabolite concentration at day-1 or day-28. Hesperetin-3ʹ-O-glucuronide, hesperetin-3ʹ-O-sulfate and hesperetin-7-O-glucuronide were quantified. Supplement flavanones had similar bioavailability to OJ, and there was no cumulative increase in excretion over 28 days. There was a non-significant decrease in blood pressure and fasting blood glucose after supplementation compared to placebo, however pulse amplitude tonometry was not affected. Augmentation index was reduced after supplementation compared to baseline. Although results from this thesis showed no significant change in CVD risk biomarkers, more work should verify the protective mechanism of hesperetin metabolites at different doses on vascular health

Effets d'une prise unique de flavanols du cacao sur la réactivité vasculaire périphérique chez des patients atteints de diabète de type 2

Thesis

Nov 2021

Anouk Tanghe

Type 2 diabetes mellitus (T2DM) represents 90 – 95 % of all diabetes cases and is characterized by β-cell dysfunction and insulin resistance leading to hyperglycemia. Hyperglycemia increases oxidative stress, inflammation, and orthosympatic activity and limits bioavailability of nitric oxide (NO), resulting in micro- (nephropathy, neuropathy, retinopathy) and macrovascular (cerebrovascular, cardiovascular, and peripheral artery disease) complications. These complications result in higher morbidity and mortality rates, decrease quality of life, and increase health economic burden. Increasing physical activity and a more balanced, healthy food intake are the first-line management. Herein, the promising vascular health benefits of nutraceuticals, like flavonoids and more specifically flavanols, have gained interest.Flavanols are natural substances present in several fruits, teas, red wines, beans, and predominantly in cocoa and are believed to beneficially affect human health. Based on epidemiological, in vitro-, animal-, and human studies, cocoa flavanols (CF) would have antioxidant properties, improve endothelial function, lower blood pressure (BP), and reduce inflammation. The mechanisms of action of CF are not yet completely understood, but it is believed that increasing NO bioavailability and –activity and antioxidative actions like inhibiting lipid peroxidation and nicotinamide adenine dinucleotide phosphate oxidase and scavenging free radicals play a key role.So far, research into the potential beneficial vascular health properties of CF in patients with diabetes mellitus (DM) is limited and demonstrated inconsistent results. However, based on the pathophysiology of diabetic vascular complications and the believed mechanisms of action of CF, one could assume that CF would exert vascular protection in T2DM subjects. Therefore, this doctoral research investigated whether CF exert vascular health benefits in patients with T2DM through the following 3 aims: (1) examine the evidence for CF-induced vascular health properties in patients with DM, (2) setup of a robust, standardized, clearly described trial protocol, and (3) investigate the acute effects of CF on peripheral vascular reactivity in patients with T2DM via execution of the described acute, randomized, double-blinded, placebo-controlled cross-over trial.First, we published a systematic review and meta-analysis on the vascular health effects of CF in patients with DM. We highlighted the need for more, robust, standardized research because of the high heterogeneity in administered intervention (dose, duration and frequency, nature of intervention), the studied population (age, sex, BMI, medical therapy, stage of disease), and measurement methods. Because of paucity of reports, we could only perform the meta-analysis on the mid/long-term effects of CF on blood pressure (BP) in patients with DM and mixed populations with increased cardiovascular risk. This meta-analysis indicated weak evidence for a reduction in diastolic BP (DBP) of, at best, 1 – 2 mmHg. No effect on systolic BP (SBP) was detected. Furthermore, CF effects on BP would be stronger in female, hypertensive, younger adults, providing a CF dose comprising at least 90 mg epicatechine (EC), and when ingested in 1 daily batch.Second, the protocol paper illustrating our setup acute, randomized, double-blinded, placebo-controlled cross-over trial was published. Here we thoroughly described our protocol trial in which we take into account the limitations in previous studies. We believe that acute studies in which subjects ingest a pure cocoa extract are the first step to gain insight in CF actions as possible confounding impact of additional fat, sugars, milk or other substances could mask/ counteract/ strengthen the effects of CF [...]

Food Containing Bioactive Flavonoids and Other Phenolic or Sulfur Phytochemicals With Antiviral Effect: Can We Design a Promising Diet Against COVID-19?

Article

Jun 2021

Since in late 2019, when the coronavirus 2 (SARS-CoV-2) pathogen of coronavirus disease 2019 (COVID-19) started to spread all over the world, causing the awful global pandemic we are still experiencing, an impressive number of biologists, infectious disease scientists, virologists, pharmacologists, molecular biologists, immunologists, and other researchers working in laboratories of all the advanced countries focused their research on the setting up of biotechnological tools, namely vaccines and monoclonal antibodies, as well as of rational design of drugs for therapeutic approaches. While vaccines have been quickly obtained, no satisfactory anti-Covid-19 preventive, or therapeutic approach has so far been discovered and approved. However, among the possible ways to achieve the goal of COVID-19 prevention or mitigation, there is one route, i.e., the diet, which until now has had little consideration. In fact, in the edible parts of plants supplying our food, there are a fair number of secondary metabolites mainly belonging to the large class of the flavonoids, endowed with antiviral or other health beneficial activities such as immunostimulating or anti-inflammatory action that could play a role in contributing to some extent to prevent or alleviate the viral infection and/or counteract the development of SARS induced by the novel coronavirus. In this review, a number of bioactive phytochemicals, in particular flavonoids, proven to be capable of providing some degree of protection against COVID-19, are browsed, illustrating their beneficial properties and mechanisms of action as well as their distribution in cultivated plant species which supply food for the human diet. Furthermore, room is also given to information regarding the amount in food, the resistance to cooking processes and, as a very important feature, the degree of bioavailability of these compounds. Concluding, remarks and perspectives for future studies aimed at increasing and improving knowledge and the possibility of using this natural complementary therapy to counteract COVID-19 and other viral pathologies are discussed.

Food Containing Bioactive Flavonoids and Other Phenolic or Sulfur Phytochemicals With Antiviral Effect: Can We Design a Promising Diet Against COVID-19?

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Jun 2021

Using polyphenols as a relevant therapy to diabetes and its complications, a review

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Diabetes is currently a worldwide health concern. Hyperglycemia, hypertension, obesity, and oxidative stress are the major risk factors that inevitably lead to all the complications from diabetes. These complications severely impact the quality of life of patients, and they can be managed, reduced, or even reverted by several polyphenols, plant extracts and foods rich in these compounds. The goal of this review is to approach diabetes not as a single condition but rather an interconnected combination of risk factors and complications. This work shows that polyphenols have multi target action and effects and they have been systematically proven to be relevant in the reduction of each risk factor and improvement of associated complication.

Hibiscus Acid Inhibitory Capacity of Angiotensin Converting Enzyme: an In Vitro and In Silico Study

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Dark chocolate intake and cardiovascular diseases: a Mendelian randomization study

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Previous intervention studies have shown some benefits of dark chocolate for the cardiovascular system, but it has not been established whether dark chocolate intake is associated with the risk of cardiovascular diseases (CVDs). To investigate the causality between dark chocolate intake and the risk of CVDs, a Mendelian randomization (MR) study was conducted. We obtained summary-level data on dark chocolate intake and CVDs from publicly available genome-wide association studies. In this MR study, the main approach was to use a fixed-effect model with inverse variance weighted (IVW) and evaluate the robustness of the results via sensitivity analysis. We found that dark chocolate intake was significantly associated with the reduction of the risk of essential hypertension (EH) (OR = 0.73; 95% CI 0.60–0.88; p = 1.06 × 10⁻³), as well as with the suggestive association to the reduced risk of venous thromboembolism (OR = 0.69; 95% CI 0.50–0.96; p = 2.81 × 10⁻²). However, no association was found between dark chocolate intake and the other ten CVDs. Our study provides evidence for a causality between dark chocolate intake and a reduced risk of EH, which has important implications for the prevention of EH in the population.

Hesperidin reduces serum levels of triglyceride after coronary artery bypass graft surgery

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Aug 2023

Hesperidin, as an antioxidant and anti‐inflammatory agent, has beneficial effects on cardiovascular diseases. This study aimed to determine the effects of hesperidin supplementation on inflammation, oxidative stress, and lipid profile in depressed coronary artery bypass graft surgery (CABG) patients. Eighty patients after coronary artery bypass graft surgery participated in this clinical trial and were randomly divided into two groups. The intervention group received 200 mg/d pure hesperidin supplement and the second group received placebo for 12 weeks. Both groups continued their usual diet. Serum concentrations of inflammatory and stress oxidative markers (hs‐CRP, P‐selectin, and ox‐LDL) were measured and compared at baseline and the end of the intervention. The changes in serum levels of triglyceride were significantly different between the two groups ( p < .05). HDL‐c significantly increased in groups but the differences between the two groups were not statistically significant ( p > .05). Hesperidin did not affect FBS, other lipid parameters, hs‐CRP, P‐selectin, and OX‐LDL ( p > .05). SBP and DBP differences were not statistically significant ( p > .05). After 12 weeks of intervention, hesperidin reduced serum levels of triglyceride in depressed post‐CABG patients.

Protective properties of AgNPs green-synthesized by Camellia sinensis on ovalbumin-induced allergic conjunctivitis

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The effects of hesperidin supplementation on cardiovascular risk factors in adults: a systematic review and dose–response meta-analysis

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Hesperidin is a naturally occurring bioactive compound that may have an impact on cardiovascular disease risks, but the evidence is not conclusive. To investigate further, this study aimed to explore the effects of hesperidin supplementation on cardiovascular risk factors in adults. A comprehensive search was conducted up to August 2022 using relevant keywords in databases such as Scopus, PubMed, Embase, Cochrane Library, and ISI Web of Science for all randomized controlled trials (RCTs). The results showed that hesperidin supplementation had a significant effect on reducing serum triglyceride (TG), total cholesterol (TC), low-density cholesterol (LDL), tumor necrosis factor-alpha (TNF-α), and systolic blood pressure (SBP), whereas weight was increased. However, no significant effect was observed on high-density cholesterol (HDL), waist circumference (WC), fasting blood glucose (FBG), insulin, homeostatic model assessment for insulin resistance (HOMA-IR), C-reactive protein (CRP), interleukin-6 (IL-6), body mass index (BMI), and diastolic blood pressure (DBP). The study also found that an effective dosage of hesperidin supplementation was around 1,000 mg/d, and a more effective duration of supplementation was more than eight weeks to decrease insulin levels. Furthermore, the duration of intervention of more than six weeks was effective in decreasing FBG levels.

Oenococcus oeni allows the increase of antihypertensive and antioxidant activities in apple cider

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This study aimed to investigate the impact of the malolactic fermentation (MLF) carried out by Oenococcus oeni on antihypertensive and antioxidant activities in cider. The MLF was induced using three strains of O. oeni. The modification in phenolic compounds (PCs) and nitrogen organic compounds, antioxidant, and antihypertensive activities were determined after MLF. Among the 17 PCs analyzed caffeic acid was the most abundant compound and phloretin, (−)-epicatechin, and myricetin were detected only in malolactic ciders, however, (−)-epigallocatechin was not detected after MLF. The evaluation of nitrogen organic compounds revealed a drop in total protein concentration (from 17.58 to 14.00 mg N/L) concomitantly with a significant release of peptide nitrogen (from 0.31 to a maximum value of 0.80 mg N/L) after MLF. In addition, an extracellular proteolytic activity was evidenced in all MLF supernatants. The FRAP activity increased reaching a maximum of 120.9 μmol FeSO4/mL and the ABTS radical-scavenging activity increased until 6.8 mmol ascorbic acid/L. Moreover, the angiotensin I-converting enzyme inhibitory activity reached a maximum value of 39.8%. The MLF conducted by O. oeni in ciders enables the increase of interesting biological activities and this finding could constitute a valuable tool to add value to final product.

Chocolate/cocoa and human health: a review

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May 2023
NETH J MED

Rabia Latif

Chocolate/cocoa has been known for its good taste and proposed health effects for centuries. Earlier, chocolate used to be criticised for its fat content and its consumption was a sin rather than a remedy, associated with acne, caries, obesity, high blood pressure, coronary artery disease and diabetes. Therefore, many physicians tended to warn patients about the potential health hazards of consuming large amounts of chocolate. However, the recent discovery of biologically active phenolic compounds in cocoa has changed this perception and stimulated research on its effects in ageing, oxidative stress, blood pressure regulation, and atherosclerosis. Today, chocolate is lauded for its tremendous antioxidant potential. However, in many studies, contradictory results and concerns about methodological issues have made it hard for health professionals and the public to understand the available evidence on chocolate’s effects on health. The purpose of this review is to interpret research done in the last decade on the benefits and risks of chocolate consumption.

Phytochemical Analysis and Habitat Suitability Mapping of Cardiocrinum cordatum (Thunb.) Makino Collected at Chiburijima, Oki Islands, Japan

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Nov 2022
MOLECULES

Cardiocrinum cordatum, known as ubayuri in Japan, has antihypertensive properties and has been shown to inhibit angiotensin-converting enzyme (ACE), which contributes to the production of angiotensin II, a hypotensive substance in the renin–angiotensin system. C. cordatum has been the subject of various studies as a useful plant and is applied as a functional food. Due to the limited distribution, loss of natural habitat by frequent natural disasters, and environmental conditions, the chemical content and biological activity of C. cordatum have been drastically affected. Obtaining a stable supply of Cardiocrinu cordatum material with high biological activity is still a challenge. Understanding the native habitat environment and suitable cultivation sites could help in solving this issue. Therefore, in the current study we investigated the effect of environmental parameters on the hypertensive and antioxidant activities of C. cordatum collected at Chiburijima, Oki Islands, Shimane Prefecture, Japan. We also predicted the habitat suitability of C. cordatum using a geographic information system (GIS) and MaxEnt model with various conditioning factors, including the topographic, soil, environmental, and climatic factors of the study area. A total of 37 individual plant samples along with soil data were collected for this study. In vitro assays of ACE inhibitory and antioxidant activity were conducted on the collected samples. The results show that plants at 14 out of 37 sites had very strong ACE inhibitory activity (IC50 < 1 mg mL−1). However, the collected plants showed no signs of strong antioxidant activity. Statistical analysis using analysis of variance (ANOVA) showed that BIO05 (F value = 2.93, p < 0.05), nitrate–nitrogen (F value = 2.46, p < 0.05), and silt (F value = 3.443, p < 0.05) significantly affected ACE inhibitory activity. On the other hand, organic carbon content (F value = 10.986, p < 0.01) was found to significantly affect antioxidant activity. The final habitat suitability map shows 3.3% very high and 6.8% high suitability regions, and samples with ACE inhibition activity were located within these regions. It is recommended further investigations and studies are conducted on C. cordatum in these locations. The prediction suitability model showed accuracy with AUC-ROC of 96.7% for the study area.

Acute Effects of Cocoa Flavanols on Blood Pressure and Peripheral Vascular Reactivity in Type 2 Diabetes Mellitus and Essential Hypertension

Article

Full-text available

Jun 2022

Background: Type 2 diabetes mellitus (T2DM) is associated with a high risk of vascular complications. Interestingly, cocoa flavanols (CF) can exert beneficial vascular effects in non-diabetic subjects. However, these effects have only been scarcely studied in T2DM. Therefore, we performed a study to assess the effects on vascular reactivity of a single dose of CF (790 mg) in T2DM and whether certain antihypertensive drugs may modulate these effects. Methods: 24 non-diabetic and 11 T2DM subjects were studied in a cross-over design. Fasting blood samples, blood pressure (BP), and arterial vasoreactivity (flow-mediated dilation) were assessed before and 70 min after capsule ingestion. Muscle microvascular reactivity was only assessed after capsule ingestion. Age, waist-to-hip ratio, BP at baseline, and the use of antihypertensive drugs were regarded as covariates in a mixed models analysis. Results: CF ingestion did not affect any parameter. However, independent of the type of capsules ingested, a decrease in diastolic BP by 3 mmHg (95% CI: −4.0; −2.0) and an increase in the change in brachial artery diameter (pre vs. post occlusion) by 0.06 mm (95% CI: 0.01; 0.12) were detected in the non-diabetic group, while they remained unchanged in the T2DM group. Conclusion: No beneficial effects of CF were detected on vascular reactivity parameters in T2DM and non-diabetic participants.

Acute Effects of Cocoa Flavanols on Blood Pressure and Peripheral Vascular Reactivity in Type 2 Diabetes Mellitus and Essential Hypertension

Article

Full-text available

Jun 2022

Danusa Dias Soares

Background: Type 2 diabetes mellitus (T2DM) is associated with a high risk of vascular complications. Interestingly, cocoa flavanols (CF) can exert beneficial vascular effects in non-diabetic subjects. However, these effects have only been scarcely studied in T2DM. Therefore, we performed a study to assess the effects on vascular reactivity of a single dose of CF (790 mg) in T2DM and whether certain antihypertensive drugs may modulate these effects. Methods: 24 non-diabetic and 11 T2DM subjects were studied in a cross-over design. Fasting blood samples, blood pressure (BP), and arterial vasoreactivity (flow-mediated dilation) were assessed before and 70 min after capsule ingestion. Muscle microvascular reactivity was only assessed after capsule ingestion. Age, waist-to-hip ratio, BP at baseline, and the use of antihypertensive drugs were regarded as covariates in a mixed models analysis. Results: CF ingestion did not affect any parameter. However, independent of the type of capsules ingested, a decrease in diastolic BP by 3 mmHg (95% CI: -4.0; -2.0) and an increase in the change in brachial artery diameter (pre vs. post occlusion) by 0.06 mm (95% CI: 0.01; 0.12) were detected in the non-diabetic group, while they remained unchanged in the T2DM group. Conclusion: No beneficial effects of CF were detected on vascular reactivity parameters in T2DM and non-diabetic participants.

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Tea (Camelliasinensis) is the world’s most widely consumed non-alcoholic beverage with essential economic and health benefits since it is an excellent source of polyphenols, catechins, amino acids, flavonoids, carotenoids, vitamins, and polysaccharides. The aim of this review is to summarize the main secondary metabolites in tea plants, and the content and distribution of these compounds in six different types of tea and different organs of tea plant were further investigated. The application of these secondary metabolites on food processing, cosmetics industry, and pharmaceutical industry was reviewed in this study. With the rapid advancements in biotechnology and sequencing technology, omics analyses, including genome, transcriptome, and metabolome, were widely used to detect the main secondary metabolites and their molecular regulatory mechanisms in tea plants. Numerous functional genes and regulatory factors have been discovered, studied, and applied to improve tea plants. Research advances, including secondary metabolites, applications, omics research, and functional gene mining, are comprehensively reviewed here. Further exploration and application trends are briefly described. This review provides a reference for basic and applied research on tea plants.

Quarter-Century Explorations of Bioactive Polyphenols: Diverse Health Benefits

Article

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Arthur J. Chu

Polyphenols, members of phytochemical superfamily rich in vegetables and fruits, include flavonoids, non-flavonoids, and phenolic acids. Their biological effects includes classical antioxidation (e.g., radical-scavenging, metal chelating, NOX inhibition, attenuation on mitochondrial respiration, inhibition on xanthine oxidase, and upregulations on endogenous antioxidant enzymes), multiple regulations on cell signaling (e.g., AMPK activation, SirT1 activation, eNOS activation, FOXO activation, NFκB inactivation, PI3K/AkT inhibition, mTORC1 inhibition, PKC inhibition, MAPK inhibition, ERK inhibition, JAK/STAT inhibition, IKK/JNK inhibition, PDE inhibition, β-catenin inactivation, downregulation on TLR expression, ACE inhibition, adiponectin elevation, attenuated ET-1 production, and K+ channel activation), and many other actions (e.g., inhibition on α-glucosidase, anticoagulation, γ-secretase inhibition, monoamine oxidase inhibition, LPL upregulation, ANGPTL4 suppression, upregulation on paraoxonase 1, PAI-1 downregulation, tPA upregulation, immunoregulation, epigenetic modulation, and altered gut microbiota). Such multi- targeting and functions exhibiting antioxidative stress and antiinflammation as major pillars along with many other antagonisms could not only afford healthy polyphenols suitable supplements for promoting health, but also advance them to therapeutic applications. This review aims to translate diverse polyphenolic biochemical actions to clinical applications in fighting against non-communicable diseases such as CVD, cancer, diabetes, obesity, neurodegeneration, inflammatory diseases (e.g., IBD, IBS, NAFLD, etc.), AMD, allergy, and autoimmunity as well as communicable infection (e.g., bacteria, fungal, and viral).

Citation: molecules Flavanols from Nature: A Phytochemistry and Biological Activity Review

Article

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Jan 2022
MOLECULES

Flavanols, a common class of secondary plant metabolites, exhibit several beneficial health properties by acting as antioxidant, anticarcinogen, cardioprotective, anti-microbial, anti-viral, and neuroprotective agents. Furthermore, some flavanols are considered functional ingredients in dairy products. Based on their structural features and health-promoting functions, flavanols have gained the attention of pharmacologists and botanists worldwide. This review collects and summarizes 121 flavanols comprising four categories: flavan-3-ols, flavan-4-ols, isoflavan-4-ols, and flavan-3,4-ols. The research of the various structural features and pharmacological activities of flavanols and their derivatives aims to lay the groundwork for subsequent research and expect to provide mentality and inspiration for the research. The current study provides a starting point for further research and development.

In silico study of potential immunonutrient-based sports supplements against COVID-19 via targeting ACE2 inhibition using molecular docking and molecular dynamics simulations

Article

Dec 2021

Use of some sports supplements can inhibit angiotensin-converting enzyme II (ACE2), a receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as reviewed through molecular docking and sequent molecular dynamics (MD) simulations against this condition. The crystal structures of ACE2 receptors of SARS-CoV-2 and SARS-CoV, applied in docking analysis, were taken from the Protein Data Bank (PDB). The receptors were then prepared using the Molecular Operating Environment (MOE), as a drug-discovery software platform for docking. Supplements such as quercetin and beta glucan (β-glucan) were the top docked compounds to ACE2 receptor though they strongly interacted with CoV target protein. The study data showed that immune responses to immunonutrient-based sports compounds (viz. quercetin and β-glucan) in Coronavirus disease 2019 (COVID-19) were essential in mounting successful immune responses by athletes. While awaiting the development of an effective vaccine, there is a need to focus on immunonutrient-based sports supplements as preventive and therapeutic options that can be implemented in a safe and quick manner to bolster immune responses in athletes. Communicated by Ramaswamy H. Sarma

Epicatechin is a promising novel inhibitor of SARS-CoV-2 entry by disrupting interactions between angiotensin-converting enzyme type 2 and the viral receptor binding domain: A computational/simulation study

Article

Dec 2021
COMPUT BIOL MED

Angiotensin-converting enzyme 2 (ACE2) is the first target of SARS-CoV-2 and a key functional host receptor through which this virus hooks into and infects human cells. The necessity to block this receptor is one of the essential means to prevent the outbreak of COVID-19. This study was conducted to find out the most eligible natural compound to suppress ACE2 to counterfeit its interaction with the viral infection. To do this, the most known compounds of sixty-six Iraqi medicinal plants were generated and retrieved from PubChem database. After preparing a library for Iraqi medicinal plants, 3663 unique ligands’ conformers were docked to ACE2 using the GLIDE tool. Results found that twenty-three compounds exhibited the highest binding affinity with ACE2. The druglikeness and toxicity potentials of these compounds were evaluated using SwissADME and Protox servers respectively. Out of these virtually screened twenty-three compounds, epicatechin and kempferol were predicted to exert the highest druglikeness and lowest toxicity potentials. Extended Molecular dynamics (MD) simulations showed that ACE2-epicatechin complex exhibited a slightly higher binding stability than ACE2-kempferol complex. In addition to the well-known ACE2 inhibitors that were identified in previous studies, this study revealed for the first time that epicatechin from Hypericum perforatum provided a better static and dynamic inhibition for ACE2 with highly favourable pharmacokinetic properties than the other known ACE2 inhibiting compounds. This study entailed the ability of epicatechin to be used as a potent natural inhibitor that can be used to block or at least weaken the SARS-CoV-2 entry and its subsequent invasion. In vitro experiments are required to validate epicatechin effectiveness against the activity of the human ACE2 receptor.

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Blood pressure disorder causes serious diseases in the cardiovascular system such as arterial hypertension. According to the World Health Organization, an estimated 1.13 billion people worldwide have hypertension, and most of them (two-thirds) live in low- and middle-income countries. It is poorly controlled and constitutes one of the leading causes of premature death. In Africa, nearly 40% of adults in many countries have high blood pressure, but most wouldn't even know it. In 2019, Algeria announced that 24% of the population suffers from the arterial hypertension and around 72% of those who were tested positive had not received treatment. Among the processes related to hypertension, the angiotensin converting enzyme I (ACE) plays an important role in the regulation of the blood pressure. The talk about the high potential of the hawthorn and rosemary plants to treat hypertension was so spread in the Algerian culture, which prompted to study the molecules of these plants and descript they behavior with the angiotensin-converting enzyme by calculating energy affinity. Using molecular docking approach, identification and evaluation of the inhibitory potential of ACE by selected herbs was attempted. In addition, and in order to identify the most suitable molecules which can be developed to oral drugs considering their adsorption, distribution, metabolism, and excretion (ADME), Lipinski’s rules were applied using free SwissADME tool. Our study provides clearer insight interaction properties of known putative inhibitors of ACE such as Caffeic acid, Quercetin, Luteolin, Eugenol, Rosmaquinone, and Rosmaquinone β, which may be developed into drugs after in-vitro and in-vivo tests and also encourage use of medicinal herbs for treatment of arterial hypertension.

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Harvesting, storage, postharvest management, and marketing of Hibiscus sabdariffa

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Full-text available

Jan 2021

Roselle (Hibiscus sabdariffa) is a useful plant with different parts utilized in several ways. The useful parts include leaves and tender shoots, stems, calyces, and seeds. They are sources of anthocyanins, flavonoids, polyphenols, organic acids, and fiber which are single-stand products, and beverages and medicinal products are obtained from them. Some products of Roselle include sauces, vegetable salads, fruit salads, creams, perfumes, marmalade, seasoning products, fibers, spices, sauces, and vegetable oils. Harvesting and postharvest procedures have a profound influence on the qualities of harvested Roselle produce: this ranges from harvesting time and standard postharvest processing procedures. Furthermore, postharvest handling has an influence on the storage time and marketability of Roselle products. However, there are huge knowledge gaps on the appropriate procedures in harvesting and processing Roselle produce. This chapter explores knowledge on harvesting, storage, postharvest management, and marketing of useful parts of Roselle (Hibiscus sabdariffa), where we focus on leaves, tender shoots, stems, calyces, and seeds. It combines information from a wide range of literature sources from several countries practicing Roselle cultivation.

Food use of whole and extracts of Hibiscus sabdariffa

Chapter

Full-text available

Jan 2021

The international demand for Hibiscus sabdariffa is high due to its valuable health properties derived from the polyphenols content available in different parts of the plant but mainly in the fruit calyx. In this chapter review, we discuss how the Roselle plant and its extracts can be used as food and raw materials in food, pharmaceuticals, and agricultural applications for health and economic benefits. The versatility of Roselle continues to attract significant research work toward the development of value-added products.

Measurement and maintenance of Hibiscus sabdariffa quality

Chapter

Full-text available

Jan 2021

The consumption of nutraceutical foods, like Roselle extracts (Hibiscus sabdariffa) from calyces and other parts, positively influences human health and prevents several diseases. This is partly due to the activities of anthocyanins, which contain appealing colorants. Also, Roselle calyces contain substantial amounts of phytochemicals, including phenolics and flavonoids. These bioactive compounds have functional applications such as antihypertensive, antioxidants, and hyperlipidemia and against low-density lipoprotein oxidation. However, they exhibit sensitivity in ultraviolet rays, high temperatures, and oxygen, which affect the quality and consequently the longevity. Furthermore, these substances deteriorate fast when subjected to varying internal and external conditions, particularly during the preparation of certain products. Therefore, to avoid quality loss and extend the shelf life of Roselle products available, various processing techniques have been proposed. This chapter reports several processing options, including heating, encapsulation, acidification, and carrier agents, for the purposes of maintaining the quality of Roselle products and quality measurement indices. Most measurement methods are explored; emphasis is given to spectrophotometric methods, particularly 1,1-diphenyl-2-picrylhydrazyl since it is simple to use.

Fruit Juices: Are They Helpful or Harmful? An Evidence Review

Article

Full-text available

May 2021

Dietary guidelines often deal with 100% fruit juice (FJ) inconsistently because it represents a source of free sugars. However, FJ also provides bioavailable micronutrients and plant bioactives at levels similar to those found in whole fruits. The present review weighs up the evidence from high-quality studies investigating a potential health harm for FJ against evidence from studies which indicate a potential health benefit. The findings reveal that FJ consumption, at moderate intakes consistent with the dietary guidelines for the US and some European countries (75–224 mL daily), does not increase the risk of obesity, type 2 diabetes, cardiovascular disease or poor glycaemic control. In contrast, regular consumption of FJ—even up to 500 mL per day in short-to-medium-term studies—appears to confer a health benefit in terms of vascular function and reduced blood pressure. Emerging evidence for cognitive health benefits requires further investigation in human trials. Observational studies report associations between FJ and nutrient adequacy and suggest that FJ consumption is associated with reduced risk of stroke. In conclusion, FJ appears to offer more benefit than risk and there appears to be no justification for discouraging FJ within a balanced diet for children and adults.

Senkung des Blutdrucks in Ruhe und bei Belastung durch regelmäßigen Schokoladenkonsum

Article

Full-text available

May 2021

Einleitung: Der Blutdruck (BD) kann neben einer medikamentösen Therapie auch durch nichtmedikamentöse Maßnahmen wie Sport und Gewichtsreduktion günstig beeinflusst werden. Ob auch durch polyphenolreiche dunkle Schokolade ein günstiger Effekt auf die BD Regulation erzielt werden kann, sollte in der folgenden Studie untersucht werden. Da insbesondere auch der BD bei Belastung, unabhängig vom BD in Ruhe, besser mit Endorganveränderungen sowie zukünftiger kardiovaskulärer Morbidität und Mortalität assoziiert ist, wurde die Wirkung dunkler Schokolade auf das BD-Verhalten nicht nur in Ruhe, sondern insbesondere auch während körperlicher Belastung untersucht. Methodik: 34 normotensive, gesunde Männer (40 ± 12 Jahre) nahmen täglich 100 g Bitterschokolade (Kakaoanteil 70 %) über einen Zeitraum von 6 Wochen ein. Der BD wurde vor Studienbeginn und nach 6 Wochen in Ruhe sowie während und nach standardisierter submaximaler Belastung auf dem Fahrradergometer (50–100 Watt, Steigerungsstufen 10 Watt/ Minute) gemessen. Ergebnisse: Nach der 6-wöchigen Schokoladeneinnahme waren der systolische und diastolische BD in Ruhe niedriger (127 ± 9/84 ± 9 mmHg) als bei der Eingangsuntersuchung (130 ± 11/87 ± 9 mmHg). Während der Ergometrie (100 Watt) war eine Senkung des systolischen BD von 167 ± 17 auf 162 ± 18 mmHg (p = 0,001) und des diastolischen BD von 87 ± 10 auf 83 ± 11 mmHg (p = 0,011) zu verzeichnen. Das Körpergewicht war nach dem Beobachtungszeitraum unverändert, Schlussfolgerung: Durch regelmäßige Einnahme polyphenolreicher dunkler Schokolade kann nicht nur der BD in Ruhe, sondern insbesondere auch während einer Belastung selbst bei Normotonikern weiter gesenkt werden. Potenzielle Nebenwirkungen wie Gewichtszunahme und Verschlechterung des Lipid- und Glukosestoffwechsels wurden nicht gefunden.

Acute Effects of Cocoa Flavanols on Blood Pressure and Peripheral Vascular Reactivity in Type 2 Diabetes Mellitus and Essential Hypertension: A Protocol for an Acute, Randomized, Double-Blinded, Placebo-Controlled Cross-Over Trial

Article

Full-text available

Mar 2021

Introduction: Patients with type 2 diabetes mellitus are at high risk to develop vascular complications resulting in high morbidity and mortality. Cocoa flavanols are promising nutraceuticals with possible beneficial vascular effects in humans. However, limited research is currently available on the vascular effects in a diabetic population with inconsistent results. Possible reasons for this inconsistency might be heterogeneity in the given intervention (dose per time and day, single dose vs. split-dose, placebo formula) and the studied population (blood pressure at baseline, duration of diabetes, use of vasoactive antihypertensive and antidiabetic drugs, sex). Therefore, we aimed to develop a randomized, double-blinded, placebo-controlled cross-over trial to investigate whether cocoa flavanols have an acute impact on blood pressure and vascular reactivity in patients with type 2 diabetes with and without arterial hypertension. Methods and Analysis: We will include participants in four groups: (i) patients with type 2 diabetes without arterial hypertension, (ii) patients with type 2 diabetes with arterial hypertension and 1 antihypertensive drug, (iii) non-diabetic participants with essential hypertension and 1 antihypertensive drug, and (iv) healthy controls. All participants will complete the same protocol on both testing days, consuming high-flavanol cocoa extract (790 mg flavanols) or placebo. Macrovascular endothelial function (flow-mediated dilation) and blood pressure will be measured before and after capsule ingestion. Forearm muscle vasoreactivity (near-infrared spectroscopy) and brachial artery blood flow (echo-doppler) will be assessed in response to a dynamic handgrip exercise test after capsule ingestion. Data will be analyzed with a random intercept model in mixed models. Clinical Trial Registration: www.Clinicaltrials.gov , identifier: NCT03722199.

Impact of cocoa flavanols on human health

Article

Mar 2021
FOOD CHEM TOXICOL

Cocoa is a source of flavanols, and these phenolic compounds exert beneficial effects on health and aging, and reduce the risk of suffering chronic diseases (cardiovascular diseases, metabolic disorders, cancer). An increasing body of evidence has emerged to suggest that cocoa flavanols potentially are important chemopreventive natural agents. This review summarizes human studies from the past two decades, providing data related to the effects derived from cocoa intake on health and disease. Most human studies have reported beneficial effects of cocoa consumption on health and chronic diseases; however, outcomes are not unequivocal. Review of human studies enable to identify different mechanisms of action for cocoa, although they are not fully understood at present. In addition, it remains unclear whether cocoa consumption should be recommended to healthy subjects or to patients and what is the appropriate dosage or duration of cocoa consumption. Elucidation of information regarding these crucial issues could lead to cocoa use as an approach for decreasing the risk of certain chronic diseases, as well as improving health and quality of life.

A Review on Recent Developments and Applications of Nanozymes in Food Safety and Quality Analysis

Article

Full-text available

Aug 2021
FOOD ANAL METHOD

Food is intricate, and food quality and safety are indispensable elements. With the rising public demands for safe and nutritious food products, a range of innovative, interdisciplinary, and multidimensional concepts have emerged in the last few decades. Nanozymes, apart from their therapeutic efficacies, are gaining increasing interest in safety and quality monitoring in the agri-food sector. These enzyme-mimetic nanomaterials are proven to detect and monitor food safety in real-time with high selectivity, stability, reliability, and recyclability. Nanozymes sourced from various nanomaterials like carbon, metal, and their oxides, metal-organic frameworks, and others offer several advantages over natural enzymes in food-based applications. Apart from real-time monitoring, these are also known for their robustness to harsh food processing environments, ease of production, and smooth and facile surface modifications. Nanozymes undergo single and multiple enzyme pathways during food analysis applications, facilitating the on-demand tailorable activity. In this context, this review briefly summarizes the working strategies and factors affecting the catalytic activity of nanozymes; the emphasis is placed on the detection of targeted analytes in the food matrix using nanozymes. Interdisciplinary tools, combined with nanozymes that aid in developing rapid on-spot identification, including spectroscopies, smartphones, electrochemiluminescence, and ELISA, are elucidated systematically. Evidenced by the rising number of nanozyme-based publications, many of the practical gaps in food analysis are narrowed. Simultaneously, some challenges like variations in recognition-to-signal patterns, optimization of nanozymes, and reproducibility of methodology need to be addressed in the future.

Evaluation of blood pressure lowering effects of cocoa flavanols in diabetes mellitus: A systematic review and meta-analysis

Article

Full-text available

Apr 2021

In healthy people, cocoa-derived flavanols (CF) improve blood pressure (BP). This meta-analysis investigates whether CF also affect BP in diabetic patients. PubMed, Web of Science, and Embase were consulted to retrieve eligible randomized controlled trials. A random-effects model and the Grades of Recommendation, Assessment, Development and Evaluation (GRADE)-approach were used for analyses and quality of evidence respectively. Of 267 citations, 11 trials were identified, studying either type 2 diabetic populations only (subgroup A) or type 2 diabetic patients plus non-diabetic subjects with increased cardiovascular risk (subgroup B1) or type 1 plus type 2 diabetic patients (subgroup B2). Mid/long-term CF consumption decreased BP slightly, however, only reaching statistical significance for diastolic BP in subgroup B1 (-1.89 mmHg, 95% CI: −3.24, −0.54, I² = 55%). Considerable heterogeneity between studies and low quality of evidence caused poor quality evidence of minimal effects of CF ingestion on BP in diabetic patients.

Effect of Tomato, Lycopene and Related Products on Blood Pressure: A Systematic Review and Network Meta-Analysis

Article

Feb 2021
PHYTOMEDICINE

Background A number of randomized controlled trials (RCTs) have been conducted to evaluate the hypotensive effects of tomato, lycopene, and related products. However, the findings were conflicting, partly due to differences in the types of products investigated. Therefore, this study aimed to assess and compare the hypotensive effects of different tomato-related preparations through a network meta-analysis based on randomized controlled trials. Study design A systematic review and network meta-analysis. Methods A network meta-analysis based on a systematic review of RCTs comparing the effect of various tomato, lycopene and related products versus placebo on blood pressure in adults was performed. PubMed, EMBASE, SCOPUS, and Clinicaltrial.gov databases were searched up to October 2020 without language restrictions. The primary outcomes were systolic and diastolic blood pressure. Mean differences (MDs) along with 95% confidence intervals (CIs) were estimated and pooled using a random-effects model. Heterogeneity was assessed using the global inconsistency test. Results A total of 11 studies including six forms of tomato, lycopene and related products met the inclusion criteria. Among these trials, eight (N = 617) and seven trials (N = 501) were included in the analysis of systolic (SBP) and diastolic blood pressure (DBP) outcomes, respectively. The standardized tomato extract (STE) significantly decreased SBP compared to placebo, with a pooled MD (95% CI) of –5.89 (–9.13 to –2.64) mmHg. The effect on DBP was not significant, with a pooled MD (95% CI) of –3.51 (–7.39 to 0.38) mmHg. Subgroup analysis in hypertensive patients showed that STE significantly reduced both SBP and DBP with pooled MDs (95% CIs) of –8.09 (–11.52 to –4.67) and –4.25 (–6.97 to –1.53) mmHg, respectively, compared to placebo. Other forms of tomato, including other dose ranges of standardized tomato extract, tomato-containing diet, lycopene-free preparation, and synthetic lycopene, did not show consistent and significant effects on either SBP or DBP in all analyses. Conclusion Standardized tomato extract (STE) significantly decreased SBP compared to placebo in a mixed population of healthy volunteers and hypertensive patients. The BP-lowering effect was more pronounced among hypertensive patients. No significant BP effects were seen with other forms of tomato, lycopene and related products in the overall population or any subgroup of the population.

Caffeic Acid Modulates Processes Associated with Intestinal Inflammation

Article

Full-text available

Feb 2021

Caffeic acid is one of the most abundant hydroxycinnamic acids in fruits, vegetables, and beverages. This phenolic compound reaches relevant concentrations in the colon (up to 126 µM) where it could come into contact with the intestinal cells and exert its anti-inflammatory effects. The aim of this investigation was to study the capacity of caffeic acid, at plausible concentrations from an in vivo point of view, to modulate mechanisms related to intestinal inflammation. Consequently, we tested the effects of caffeic acid (50-10 µM) on cyclooxygenase (COX)-2 expression and prostaglandin (PG)E2, cytokines, and chemokines (IL-8, monocyte chemoattractant protein-1 -MCP-1-, and IL-6) biosynthesis in IL-1β-treated human myofibroblasts of the colon, CCD-18Co. Furthermore, the capacity of caffeic acid to inhibit the angiotensin-converting enzyme (ACE) activity, to hinder advanced glycation end product (AGE) formation, as well as its antioxidant, reducing, and chelating activity were also investigated. Our results showed that (i) caffeic acid targets COX-2 and its product PGE2 as well as the biosynthesis of IL-8 in the IL-1β-treated cells and (ii) inhibits AGE formation, which could be related to (iii) the high chelating activity exerted. Low anti-ACE, antioxidant, and reducing capacity of caffeic acid was also observed. These effects of caffeic acid expands our knowledge on anti-inflammatory mechanisms against intestinal inflammation.

Phenolic Compounds in Plant Materials: Problems and New Analytical Solutions

Chapter

Jun 2017

The improvement of the functional condition of micro-vascular endothelium among the aged people with metabolic syndrome under quercetin influence

Article

Oct 2020

The Aim of study is the impact of course application of quercetin on the functional state of the endothelium of the microvessels in elderly people with metabolic syndrome. Materials and methods. We examined 110 patients (55 primary and 55 control patients) with metabolic syndrome (MS). Patients in the main group (n = 55) received quercetin ("Kvertin", chewing tablets manufactured by PJSC "Borshchagovsky KFZ", 80 mg 3 times a day) during 3 months. The control group patients (n = 55) received placebo tablets. The volume velocity of skin blood flow in the region of the middle third of the inner surface of the forearm was determined using the laser doppler flowmetry (LDP) on the apparatus BLF-21D (Transonic Systems Inc, USA). The functional state of the endothelium of microvessels was examined in a sample with post-exclusive hyperemia by clamping shoulder vessels of with a cuff for 3 minutes, in which the pressure exceeded the systolic blood pressure of the subject by 50 mm Hg. Blood pressure was measured by the Erkameter 3000 (Germany) mercury sphygmomanometer on the shoulder artery in accordance with ESH recommendations. Results. In the group of patients receiving quercetin, when performing a test with post-occlusive hyperemia, there was a statistically significant increase in the maximum volumetric velocity of the skin blood flow and the duration of the recovery period, the volumetric velocity of the skin blood flow to the initial level, which indicates an improvement in the vasomotor function of the microvessel endothelium. Improvement of the functional state of the endothelium occurred in 38 of 55 patients (69%) examined and was accompanied by a significant decrease in the level of systolic and diastolic blood pressure. Patients in the control group showed no improvement in the indices of vasomotor function of the microvessel endothelium. Conclusions. Course application of quercetin improves the functional state of the endothelium of microvessels, which helps to lower blood pressure in patients with metabolic syndrome. Key words: metabolic; syndrome; quercetin; functional state of the endothelium; arterial pressure

Flavan‐3‐ols: Catechins and Proanthocyanidins

Chapter

Dec 2020

This chapter comprehensively summarizes the most recent evidence regarding one of the largest and most representative flavonoid subclasses, namely flavan‐3‐ols. Flavan‐3‐ol monomers and polymers have been found to be present in several fruits, vegetables, and seeds and in widely consumed beverages, such as tea, red wine, and chocolate. For this reason, numerous epidemiological and in vivo studies have been performed in order to elucidate whether the intake of these compounds may play a role in protection from cardiovascular, neurological, and metabolic diseases. Thus, although the literature has focused on the molecular actions of the flavan‐3‐ols present in planta, more recent studies of absorption, distribution, metabolism, and excretion have revealed that flavan‐3‐ols undergo an extensive rearrangement along the lower gastrointestinal tract. Actually, microbial and hepatic processes lead mainly to the release into the bloodstream and tissues of smaller and more polar metabolites, like phenyl‐γ‐valerolactones, phenylvaleric and phenylpropionic acids and their conjugates, which might be the real biological effectors in certain (patho)physiological scenarios. In conclusion, the main goal of the chapter is to give an overview of the most recent findings on flavan‐3‐ol bioavailability and health effects, highlighting the metabolic fate of these compounds, a key aspect for the design and conduction of in vivo studies aiming at addressing the health effects attributed to flavan‐3‐ols and/or their metabolites.

Vegetable Oils in Pharmaceutical Industry

Chapter

Jan 2024

Effect of Coffee-Corn Mix on Hypertensive Mice on Biomarkers of Nitric Oxide, eNOS, Sodium, and ACE Serum Levels

Article

Aug 2023

Hypertension is a major determinant of morbidity and mortality worldwide. Hypertension is the most common cause of death in Southeast Asia. The pathophysiology of hypertension is complex and not fully understood. Increased oxidative stress is considered one of the main mechanisms involved in the pathogenesis of endothelial dysfunction leading to hypertension. Therefore, antioxidant therapy can be an alternative option to prevent endothelial damage and hypertension. Robusta coffee and corn are high sources of antioxidants. This study aimed to analyze the effect of the coffee-corn mixture on NO, eNOS, sodium, and ACE serum levels in hypertensive rats. This research is an experimental laboratory study with a post-test only control group design. Robusta coffee and yellow corn samples were roasted at 180°C for 10 minutes. Rats were induced by DOCA salt and given a mixture of coffee-corn in a ratio of 75%: 25% and 50%: 50% for two weeks. After treatment, the levels of NO, eNOS, ACE, and F2-isoprostane from blood serum were measured. The results showed that there was no significant difference in serum Nitric Oxide levels in the negative, positive control group and the treatment group after treatment. There was a significant increase in eNOS levels and a significant decrease in serum sodium, ACE, and F2-isoprostane levels in the negative, positive, and treatment groups. In the path analysis, it was found that the administration of the coffee-corn mixture (50%:50%) can reduce blood pressure through two pathways, namely a decrease in the level of F2-isoprostane, which causes a decrease in sodium levels and a direct decrease in sodium levels.

Enhanced antihypertensive potential of fermented pomegranate juice: The contribution of phenolic compounds biotransformation and the resultant angiotensin-I-converting enzyme inhibition mechanism

Article

Oct 2022
FOOD CHEM

Current research on plant food-derived phenolic compounds as angiotensin-I-converting enzyme (ACE) inhibitors has been well documented. Pomegranate juice (PJ) has been reported positively contributed to ACE inhibition. Microbial fermentation is a preferable technique to regulate the biotransformation of phenolic compounds and their bioaccessibility, therefore promoting the ACE inhibitory activity in plant food with antihypertension potential. In this study, the remarkable improvements of ACE inhibitory activity and antioxidant capacity in Lactobacillus plantarum fermented PJ were observed. A consecutive study of phenolic compounds biotransformation, ACE inhibition kinetics and structure-activity relationship were performed. This study firstly highlights the relationship between the enhanced ACE inhibitory activity in fermented PJ and the biotransformation of phenolic compounds, providing a new way to reinforce plant food ACE inhibition potential by microbial fermentation.

The effect of nigella supplementation on blood pressure: A systematic review and dose-response meta-analysis

Article

Aug 2022

This study was performed to assess the effect of nigella supplementation on blood pressure levels among the adult population. A comprehensive search was carried out through PubMed, Scopus, Web of Science, and Cochrane Library by using relevant keywords to find out the randomized clinical trials evaluating the effect of nigella administration on systolic blood pressure (SBP) and diastolic blood pressure (DBP). A random-effect model was applied to achieve the overall effect size. Subgroup analysis and meta-regression were used to explore the source of heterogeneity and the effects of the possible moderators. Of the twenty-two trials that were eligible for the present study, seventeen studies consisting of 1048 participants were included in the meta-analysis. The results indicated that nigella administration could significantly reduce both SBP (−4.58 mmHg; 95%CI: −6.22, −2.94) and DBP (−3.08 mmHg; 95%CI: −4.62, −1.55). Subgroup analysis did not show any superiority between subgroups of variables. Dose-response analysis detected a nonlinear association between dose and duration of administration and change in blood pressure outcomes, highlighting that maximum SBP and DBP reduction was experienced at 2000 mg/day and 8 weeks of nigella administration, respectively. The present study suggests that nigella supplementation can be beneficial for managing blood pressure.

Antioxidant and Angiotensin-Converting Enzyme Inhibitory Activities of Fractionated Extract of Combretum micranthum Leaves

Article

Full-text available

Jul 2022
J Biol Sci

IDENTIFIKASI POTENSI SENYAWA ISOFLAVON DAN QUERCETIN DAN PERBANDINGAN IKATAN TERHADAP ACE (ANGIOTENSIN-CONVERTING ENZYME) MENGGUNAKAN STUDI IN SILICO

Article

Jan 2022

Prevalensi hipertensi di Indonesia tergolong tinggi, sekitar 29,1% pada laki-laki dan perempuan sebesar 26,6%. Penderita hipertensi di Jawa Timur juga tergolong tinggi, sebanyak 31.789 orang. Solusi alternatif dalam penelitian ini, memanfaatkan isoflavon dan quercetin sebagai antihipertensi. Isolavon dan quercetin merupakan seyawa fenolik yang mampu berikatan dengan Angiotensin Converting Enzyme(ACE) dan mempengaruhi tekanan darah. Penelitian ini mengidentifikasi potensi senyawa isoflavon dan quercetin serta perbandingan ikatan antara isoflavon dan quercetin terhadap ACE dengan menggunakan perangkat lunak Hex 8. Penelitian ini adalah deskriptif kuantitatif dengan penelusuran melalui metode in silico (pengunduhan molekul dan penambatan molekul) secara komputerisasi. Softwareatau aplikasi yang digunakan pada penelitian ini adalah pass server dan HEX 8.0. Hasil visualisasi penambatan molekul ditampilkan dengan perangkat lunak Discovery Studio. Hasil penelitian ini menunjukkan bahwa senyawa quercetin dan isoflavone berpotensi sebagai vasoprotektor. Energi penambatan molekul Isoflavon terhadap ACE sebesar -194,66 kkal.mol. Quercetin sebesar -236,47 kkal.mol, Captopril sebesar -494.56 kkal/mol. Energi penambatan ligan isoflavon dan quercetin terhadap ACE (Angiotensin Converting Enzyme) lebih besar daripada penambatan ligan Captopril terhadap ACE (Angiotensin Converting Enzyme). Hasil penelitian ini memberi harapan potensi penggunaan senyawa ligan sebagai antihipertensi namun memerlukan penelitian lebih lanjut.

ESTRATÉGIAS NUTRICIONAIS NO COMBATE À DEPRESSÃO

Chapter

Jan 2022

Medicinal and therapeutic potential of Roselle (Hibiscus sabdariffa)

Chapter

Jan 2021

The Roselle (Hibiscus sabdariffa) is being extensively used in folk medicine owing to its rich phytochemical profile including polyphenols, especially anthocyanins, organic acids, and polysaccharides, thereby offering greater prospects in therapeutic and medicinal uses. The Roselle infusions or decoctions present significant therapeutic options against various degenerative ailments such as hyperlipidemia, hypertension, diabetics, cancer, hepatoprotection, nephroprotection, and many others. The previous work supports the scientific hypothesis that Roselle plant enriched with bioactive constituents plays an imperative role in the management of degenerative and chronic diseases that are associated with oxidative stress. However, well-designed animal and human studies are underway to precisely quantify the therapeutic potential of purified phytochemical preparations. This work aims to review and document the scientific evidence about the potential therapeutic uses of the Roselle plant.

Antihypertensive Potential of Plant Foods: Research Progress and Prospect of Plant-Derived Angiotensin-Converting Enzyme Inhibition Compounds

Article

May 2021

Cocoa and Insulin Resistance: Protective Effects on Metabolic Syndrome

Chapter

Oct 2015

Quercetin and Its Metabolites Inhibit Recombinant Human Angiotensin-Converting Enzyme 2 (ACE2) Activity

Article

Full-text available

Nov 2020
J AGR FOOD CHEM

Angiotensin-converting enzyme 2 (ACE2) is a host receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Inhibiting the interaction between the envelope spike glycoproteins (S-proteins) of SARS-CoV-2 and ACE2 is a potential antiviral therapeutic approach, but little is known about how dietary compounds interact with ACE2. The objective of this study was to determine if flavonoids and other polyphenols with B-ring 3′,4′-hydroxylation inhibit recombinant human (rh)ACE2 activity. rhACE2 activity was assessed with the fluorogenic substrate Mca-APK(Dnp). Polyphenols reduced rhACE2 activity by 15−66% at 10 μM. Rutin, quercetin-3-O-glucoside, tamarixetin, and 3,4-dihydroxyphenylacetic acid inhibited rhACE2 activity by 42−48%. Quercetin was the most potent rhACE2 inhibitor among the polyphenols tested, with an IC50 of 4.48 μM. Thus, quercetin, its metabolites, and polyphenols with 3′,4′-hydroxylation inhibited rhACE2 activity at physiologically relevant concentrations in vitro.

Complementary and Alternative Medicine Use in Hypertension: The Good, the Bad, and the Ugly: Hypertension Treatment From Nature – Myth or Fact?

Chapter

Jan 2019

Thirty six percent of people in USA and Canada regularly use complementary and alternative medicine (CAM) for the prevention and treatment of different diseases, including hypertension. Generally, majority of the hypertensive patients do not disclose the use of such remedies, and also health care providers do not usually ask their hypertensive patients if they use CAM. The widespread consumption of CAM in hypertension requires clear understanding of their underlying mechanism of action, efficacy and safety. This chapter will provide a comprehensive list of CAM commonly used by Americans for the prevention and treatment of hypertension as well as their postulated mechanism of action. Modulation of drug metabolizing enzymes and their safety will also be covered along with the clinical consequences, i.e. drug-herb or herb-disease interactions. patients and healthcare providers should also be careful with using CAM therapies, because not only is there minimal evidence that several CAM products work to treat hypertension, but their safety hasn't been well-established.

KINSELLA JE: Inhibition of oxidation of human low - density lipoprotein by phenolic substances in red wine

Article

Full-text available

Feb 1993

The "French paradox" (apparent compatibility of a high fat diet with a low incidence of coronary atherosclerosis) has been attributed to the regular drinking of red wine. However, the alcohol content of wine may not be the sole explanation for this protection. Red wine also contains phenolic compounds, and the antioxidant properties of these may have an important role. In in-vitro studies with phenolic substances in red wine and normal human low-density lipoprotein (LDL) we found that red wine inhibits the copper-catalysed oxidation of LDL. Wine diluted 1000-fold containing 10 mumol/L total phenolics inhibited LDL oxidation significantly more than alpha-tocopherol. Our findings show that the non-alcoholic components of red wine have potent antioxidant properties toward oxidation of human LDL.

Molecular Cloning of Human Testicular Angiotensin-Converting Enzyme: The Testis Isozyme is Identical to the C-Terminal Half of Endothelial Angiotensin-Converting Enzyme

Article

Full-text available

Nov 1989

Angiotensin-converting enzyme (ACE; EC 3.4.15.1) is a zinc-containing dipeptidyl carboxypeptidase widely distributed in mammalian tissues and is thought to play a critical role in blood pressure regulation. Testis contains a unique, androgen-dependent ACE isozyme of unknown function. We have determined the cDNA sequence for human testicular ACE; it encodes a protein that is identical, from residue 37 to its C terminus, to the second half or C-terminal domain of the endothelial ACE sequence [Soubrier, F., Alhenc-Gelas, F., Hubert, C., Allegrini, J., John, M., Tregear, G. & Corvol, P. (1988) Proc. Natl. Acad. Sci. USA 85, 9386-9390]. The full-length human testis ACE cDNA was constructed from a composite of cloned cDNAs, obtained by a combination of (i) immunoscreening and hybridization screening of a human testicular cDNA library in lambda gt11 and (ii) hybridization screening of human testis cDNAs constructed with ACE-specific primers and amplified by the polymerase chain reaction. The protein sequence inferred consists of a 732-residue preprotein including a 31-residue signal peptide. The mature polypeptide has a molecular weight of 80,073. The testis enzyme contains the second of the two putative metal-binding sites (His-Glu-Met-Gly-His) identified in endothelial ACE. This indicates that the functionally active catalytic site is within the C-terminal domain of the endothelial enzyme, accounting for the previous finding that these two structurally dissimilar isozymes are virtually identical catalytically. Of 22 testis ACE cDNAs cloned and sequenced, 3 have unique 5' regions, consisting of inserted, deleted, or substituted sequences up to 328 base pairs long, which have apparently arisen by alternative pre-mRNA splicing.

Frankel EN, Kanner J, German JB, Parks E, Kinsella JE. Inhibition of oxidation of human low-density lipoprotein by phenolic substances in red wine. Lancet 341, 454-457

Article

Full-text available

Mar 1993

Identification of Procyanidins in Cocoa (Theobroma cacao) and Chocolate Using High Performance Liquid Chromatography/Mass Spectrometry

Article

Full-text available

Feb 1999

Monomeric and oligomeric procyanidins present in cocoa and chocolate were separated and identified using a modified normal-phase high-performance liquid chromatography (HPLC) method coupled with on-line mass spectrometry (MS) analysis using an atmospheric pressure ionization electrospray chamber. The chromatographic separation was achieved using a silica stationary phase in combination with a gradient ascending in polarity. This qualitative report confirms the presence of a complex series of procyanidins in raw cocoa and certain chocolates using HPLC/MS techniques. Although both cocoa and chocolate contained monomeric and oligomeric procyanidin units 2-10, only use of negative mode provided MS data for the higher oligomers (i.e., >pentamer). Application of this method for qualitative analysis of proanthocyanidins in other food products and confirmation of this method as a reliable quantitative tool for determining levels of procyanidins in cocoa, chocolate, and other food products are currently being investigated.

Middleton Jr E, Kandaswami C & Theoharides TC: The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease and cancer. Pharmacol. Rev. 52, 673-751

Article

Full-text available

Jan 2001

Flavonoids are nearly ubiquitous in plants and are recognized as the pigments responsible for the colors of leaves, especially in autumn. They are rich in seeds, citrus fruits, olive oil, tea, and red wine. They are low molecular weight compounds composed of a three-ring structure with various substitutions. This basic structure is shared by tocopherols (vitamin E). Flavonoids can be subdivided according to the presence of an oxy group at position 4, a double bond between carbon atoms 2 and 3, or a hydroxyl group in position 3 of the C (middle) ring. These characteristics appear to also be required for best activity, especially antioxidant and antiproliferative, in the systems studied. The particular hydroxylation pattern of the B ring of the flavonoles increases their activities, especially in inhibition of mast cell secretion. Certain plants and spices containing flavonoids have been used for thousands of years in traditional Eastern medicine. In spite of the voluminous literature available, however, Western medicine has not yet used flavonoids therapeutically, even though their safety record is exceptional. Suggestions are made where such possibilities may be worth pursuing.

Nijveldt RJ, van Nood E, van Hoorn DEC, Boelens PG, van Norren K, van Leeuwen PAMFlavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr 74: 418-425

Article

Full-text available

Nov 2001

The aim of this review, a summary of the putative biological actions of flavonoids, was to obtain a further understanding of the reported beneficial health effects of these substances. Flavonoids occur naturally in fruit, vegetables, and beverages such as tea and wine. Research in the field of flavonoids has increased since the discovery of the French paradox,ie, the low cardiovascular mortality rate observed in Mediterranean populations in association with red wine consumption and a high saturated fat intake. Several other potential beneficial properties of flavonoids have since been ascertained. We review the different groups of known flavonoids, the probable mechanisms by which they act, and the potential clinical applications of these fascinating natural substances.

Procyanidin dimer B2 [epicatechin-(4β-8)-epicatechin] in human plasma after the consumption of a flavanol-rich cocoa–

Article

Full-text available

Nov 2002

Epidemiologic studies have linked flavonoid-rich foods with a reduced risk of cardiovascular mortality. Some cocoas are flavonoid-rich and contain the monomeric flavanols (-)-epicatechin and (+)-catechin and oligomeric procyanidins formed from these monomeric units. Both the monomers and the oligomers have shown potential in favorably influencing cardiovascular health in in vitro and preliminary clinical studies. Although previous investigations have shown increasing concentrations of (-)-epicatechin in human plasma after cocoa consumption, no information is available in the published literature regarding the presence of procyanidins in human plasma. This study sought to determine whether procyanidins can be detected and quantified in human plasma after acute consumption of a flavanol-rich cocoa. Peripheral blood was obtained from 5 healthy adult subjects before (baseline, 0 h) and 0.5, 2, and 6 h after consumption of 0.375 g cocoa/kg body wt as a beverage. Plasma samples were analyzed for monomers and procyanidins with the use of reversed-phase HPLC with coulometric electrochemical array detection and liquid chromatography-tandem mass spectrometry. Procyanidin dimer, (-)-epicatechin, and (+)-catechin were detected in the plasma of human subjects as early as 0.5 h (16 +/- 5 nmol/L, 2.61 +/- 0.46 micro mol/L, and 0.13 +/- 0.03 micro mol/L, respectively) after acute cocoa consumption and reached maximal concentrations by 2 h (41 +/- 4 nmol/L, 5.92 +/- 0.60 micro mol/L, and 0.16 +/- 0.03 micro mol/L, respectively). Dimeric procyanidins can be detected in human plasma as early as 30 min after the consumption of a flavanol-rich food such as cocoa.

Maintenance of Normal Blood Pressure and Renal Functions Are Independent Effects of Angiotensin-converting Enzyme

Article

Full-text available

Jul 2003

Angiotensin-converting enzyme (ACE) is expressed in many tissues, including vasculature and renal proximal tubules, and its genetic ablation in mice causes abnormal renal structure and functions, hypotension, and male sterility. To test the hypothesis that specific physiological functions of ACE are mediated by its expression in specific tissues, we generated different mouse strains, each expressing ACE in only one tissue. Here, we report the properties of two such strains of mice that express ACE either in vascular endothelial cells or in renal proximal tubules. Because of the natural cleavage secretion process, both groups also have ACE in the serum. Both groups were as healthy as wild-type mice, having normal kidney structure and fluid homeostasis, though males remained sterile, because they lack ACE expression in sperm. Despite equivalent serum ACE and angiotensin II levels and renal functions, only the group that expressed ACE in vascular endothelial cells had normal blood pressure. Expression of ACE, either in renal proximal tubules or in vasculature, is sufficient for maintaining normal kidney functions. However, for maintaining blood pressure, ACE must be expressed in vascular endothelial cells. These results also demonstrate that ACE-mediated blood pressure maintenance can be dissociated from its role in maintaining renal structure and functions.

Dietary flavanols and procyanidin oligomers from cocoa (Theobroma cacao) inhibit platelet function

Article

Full-text available

Jul 2003

Flavonoids may be partly responsible for some health benefits, including antiinflammatory action and a decreased tendency for the blood to clot. An acute dose of flavanols and oligomeric procyanidins from cocoa powder inhibits platelet activation and function over 6 h in humans. This study sought to evaluate whether 28 d of supplementation with cocoa flavanols and related procyanidin oligomers would modulate human platelet reactivity and primary hemostasis and reduce oxidative markers in vivo. Thirty-two healthy subjects were assigned to consume active (234 mg cocoa flavanols and procyanidins/d) or placebo (< or = 6 mg cocoa flavanols and procyanidins/d) tablets in a blinded parallel-designed study. Platelet function was determined by measuring platelet aggregation, ATP release, and expression of activation-dependent platelet antigens by using flow cytometry. Plasma was analyzed for oxidation markers and antioxidant status. Plasma concentrations of epicatechin and catechin in the active group increased by 81% and 28%, respectively, during the intervention period. The active group had significantly lower P selectin expression and significantly lower ADP-induced aggregation and collagen-induced aggregation than did the placebo group. Plasma ascorbic acid concentrations were significantly higher in the active than in the placebo group (P < 0.05), whereas plasma oxidation markers and antioxidant status did not change in either group. Cocoa flavanol and procyanidin supplementation for 28 d significantly increased plasma epicatechin and catechin concentrations and significantly decreased platelet function. These data support the results of acute studies that used higher doses of cocoa flavanols and procyanidins.

Vascular Effects of Cocoa Rich in Flavan-3-Ols

Article

Full-text available

Sep 2003
J Am Med Assoc

Chocolate and Blood Pressure in Elderly Individuals with Isolated Systolic Hypertension [5]

Article

Full-text available

Sep 2003
J Am Med Assoc

Tea Intake Is Inversely Related to Blood Pressure in Older Women

Article

Full-text available

Sep 2003

Tea is rich in polyphenols, which have activities consistent with blood pressure-lowering potential. The effects of long-term regular ingestion of tea on blood pressure remain uncertain. We investigated the relationships of tea intake and a biomarker of exposure to tea-derived polyphenols (4-O-methylgallic acid) with blood pressure in a cross-sectional study of 218 women > 70 y old. Clinic blood pressures were measured and tea intake was assessed using a 24-h dietary recall; 4-O-methylgallic acid was measured for the same period in a 24-h urine sample. Mean (95% CI) daily tea intake was 525 (475, 600) mL. Mean systolic and diastolic blood pressures were 138.1 (135.6, 140.6) and 73.5 (72.1, 74.9) mm Hg. Higher tea intake and higher 4-O-methylgallic acid excretion were associated with significantly lower systolic (P = 0.002 and P = 0.040, respectively) and diastolic (P = 0.027 and P < 0.001, respectively) blood pressures. A 250 mL/d (1 cup) increase in tea intake was associated with a 2.2 (0.8, 3.6) mm Hg lower systolic blood pressure and a 0.9 (0.1, 1.7) mm Hg lower diastolic blood pressure. The observed associations for both tea intake and 4-O-methylgallic acid are consistent with the hypothesis that long-term regular ingestion of tea may have a favorable effect on blood pressure in older women.

Metabolism of dietary procyanidins in rats

Article

Full-text available

Nov 2003
FREE RADICAL BIO MED

Procyanidins are major dietary polyphenols made of elementary flavan-3-ol (epi)catechin units. They have antioxidant properties and may contribute to health benefits in humans, but little is known about their metabolic fate. We compared here the metabolism of procyanidin dimer B3, trimer C2, and polymer isolated from willow tree catkins to that of catechin monomer in rats. These compounds were administered in the rat diet (0.1%, w/w) for 5 d and their metabolites estimated in 24 h urine. In rats fed procyanidins, neither parent compound nor catechin derivatives could be detected in contrast to animals fed catechin monomer, which excreted large amounts of catechin and its 3'-O-methylated form (25.7 +/- 0.6%). On the other hand, 16 metabolites of microbial origin were detected and identified as phenylvaleric, phenylpropionic, phenylacetic, and benzoic acid derivatives. Their total yields significantly decreased from the catechin monomer (10.6 +/- 1.1%) to the procyanidin dimer (6.5 +/- 0.2%), trimer (0.7 +/- 0.1%), and polymer (0.5 +/- 0.1%). Therefore, the degree of procyanidin polymerization has a major impact on their fate in the body characterized by a poor absorption through the gut barrier and a limited metabolism by the intestinal microflora as compared to catechin. This will have to be considered to explain the health effects of procyanidins. The contribution of their microbial metabolites should also be further investigated.

The effects of plant flavonoids on mammalian cells: Implications for inflammation, heart disease and cancer

Article

Jan 2002

Flavonoids: A review of probable mechanisms of action and potential applications

Article

Oct 2001

[19] Astacin

Article

Dec 1995

Levels of Flavan3-ols in French Wines

Article

Oct 1999

French wines are abundant sources of phenolic compounds. The content of several catechins, i.e., (+)-catechin, (-)-epicatechin, dimers B1, B2, B3, and B4, trimers C1, and trimer 2 (T2), of 160 French wines was determined by HPLC with UV detection. Red wines (n = 95) were found to have high levels of catechins, ranging from 32.8 to 209.8 mg/L (mean concentration 114.5 mg/L) for (+)catechin, from 22.1 to 130.7 mg/L (mean concentration 75.7 mg/L) for (-)-epicatechin, from 7.8 to 39.1 mg/L (mean concentration 25.4 mg/L) for B1, from 18.3 to 93 mg/L (mean concentration 47.4 mgn) for B2, from 21.4 to 215.6 mg/L (mean concentration 119.6 mg/L) for B3, from 20.2 to 107.2 mg/L (mean concentration 81.9 mg/l) for B4, from 8.6 to 36.9 mg/L (mean concentration 26.3 mg/L) for C1, and from 26.7 to 79.3 mg/L (mean concentration 67.1 mg/L) for T2. White and rose wines (n. = 57 and n = 8) were found to have low levels of (+)-catechin (mean concentrations 9.8 and 10.6 mg/L, respectively) and (-)-epicatechin (mean concentrations 5.3 and 6.5 mg/L, respectively). These data provide a basis for the epidemiological evaluation of catechin intake by the consumption of French wine.

Angiotensin-Converting Enzyme in Epithelial and Neuroepithelial Cells

Article

Jul 1983
NEUROENDOCRINOLOGY

Angiotensin-converting enzyme (CE) occurs in three types of cell:endothelial, epithelial, and neuroepithelial. In all three, it appears to be bound to plasma membrane. With antisera to the human enzyme, CE is demonstrated in paraffin sections on the apical surface of epithelial cells in the proximal tubule of the kidney, the mucosa of the small intestine, the syncytial trophoblast of the placenta, and the choroid plexus. Epithelial CE is characteristically found on microvillous surfaces in contact with an effluent, well placed to act on substrate in flux. In the brain, CE occurs in nerve fibers and terminals, mainly mesiobasally and in basal ganglia. Mesiobasal CE coincides with other components of the renin-angiotensin system (RAS) in the choroid/ventricular fluid, the subfornical organ, and the magnocellular neurosecretory system of the hypothalamus. Extrapyramidal CE, however, may not be related to the RAS. In the substantia nigra and the globus pallidus, the enzyme has the same cellular distribution as two putative neuromodulators, substance P and enkephalin, the latter a known substrate of CE.

Method for Measuring Antioxidant Activity and Its Application to Monitoring the Antioxidant Capacity of Wines

Article

Feb 1999

A novel method for measuring the antioxidant activity using N,N-dimethyl-p-phenylenediamine (DMPD) was developed. The radical cation of this compound gives a stable colored solution and a linear inhibition of color formation can be observed in the presence of 0.2−11 μg of TROLOX. The experimental protocol, which is rapid and inexpensive, ensures sensitivity and reproducibility in the measure of antioxidant activity of hydrophilic compounds. The effectiveness of the DMPD method on real foods was verified by evaluating the antioxidant ability of wine samples coming from different areas of Campania, Italy. Antioxidant capacity of wines is strictly related to the amount of phenolic compounds. The results obtained by the DMPD method are very similar to those obtained on the same samples when the radical cation of 2,2‘-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) (Miller et al., 1996) was used. Keywords: Antioxidant activity; DMPD; radical cation; ABTS; wine

Critical Factors of Vanillin Assay for Catechins and Proanthocyanidins

Article

Sep 1998

Several parameters mostly affecting the precision and accuracy of vanillin assay were reexamined and optimized. The reexamination was performed both by vanillin reaction with catechins and by vanillin reaction with purified proanthocyanidins. In addition to the acid nature and concentration, the reaction time, the temperature, and the vanillin concentration, other factors such as the water content, the presence of interfering substances, and the standard utilized, for both vanillin reaction with catechins and vanillin reaction with proanthocyanidins, were also important. However, the kinetics of the two types of reactions were markedly different. For estimating accurately catechins or proanthocyanidins that exist simultaneously in plant tissues, it is necessary to preliminarily separate them from each other. Keywords: Catechins; proanthocyanidins; vanillin assay

A Critical Evaluation of the Vanillin Reaction as an Assay for Tannin in Sorghum Grain

Article

May 1978

Several parameters of the vanillin assay were examined to determine which must be most closely controlled to ensure accuracy and reproducibility. A 20-min extraction in methanol was found to be adequate. When corrected for background color, the modified vanillin assay was found to give nearly identical values with those obtained with the regular vanillin assay, except with group II sorghum. The reactions of tannin and catechin, the usual standard, with vanillin were found to differ markedly in reaction kinetics. Assays of purified tannin showed that use of catechin equivalents overestimates tannin content The assay was found to be extremely temperature dependent. Revised procedures for the vanillin assay are presented which give excellent reproducibility.

Antioxidant Capacities and Phenolics Levels of French Wines from Different Varieties and Vintages

Article

Jun 2001

Phenolics from grapes and wines can play a role against oxidation and development of atherosclerosis. Levels of phenolics, major catechins [(+)-catechin, (−)-epicatechin, procyanidin dimers B1, B2, B3, and B4], phenolic acids (gallic acid and caffeic acid), caftaric acid, malvidin-3-glucoside, peonidin-3-glucoside, and cyanidin-3-glucoside were quantified by HPLC with UV detection for 54 French varietal commercial wines taken from southern France to study the antioxidant capacity and the daily dietary intake of these compounds for the French population. The highest antioxidant capacity was obtained with red wines and ranged from 12.8 mmol/L (Grenache) to 25.2 mmol/L (Pinot Noir). For white wines, Chardonnay enriched in phenolics by special wine-making was found to have an antioxidant capacity of 13.8 mmol/L, comparable to red wine values. For red wines classified by vintages (1996−1999) antioxidant capacities were 20 mmol/L and then decreased to 13.4 mmol/L for vintages 1995−1991. Sweet white wines have 1.7 times more antioxidant capacity (3.2 mmol/L) than dry white wines (1.91 mmol/L). On the basis of a still significant French wine consumption of 180 mL/day/person, the current daily intake of catechins (monomers and dimers B1, B2, B3, and B4) averaged 5 (dry white wine), 4.36 (sweet white wines), 7.70 (rosé wines), 31.98 (red wines), and 66.94 (dry white wine enriched in phenolic) mg/day/resident for the French population. Red wine, and particularly Pinot Noir, Egiodola, Syrah, Cabernet Sauvignon, and Merlot varieties, or Chardonnay enriched in phenolics during wine-making for white varieties contribute to a very significant catechin dietary intake. Keywords: Wine; phenolics; antioxidant capacity; levels; varieties; vintages

Angiotensin I converting enzyme in human intestine and kidney

Article

Jan 1986

The localization of immunoreactive angiotensin I-converting enzyme (ACE) has been investigated at the optical and ultrastructural level with anti-human ACE antibodies in the human kidney and small intestine. In both tissues ACE was found in blood vessels and in extravascular situation in the absorptive epithelial cells of intestinal mucosa and renal proximal tubules. Ultrastructural immunohistochemistry showed that in intestinal and renal proximal tubular cells ACE was prominent in microvilli and brush borders. In the kidney ACE was also present on the basolateral part of the plasmalemmal membrane, where it may contribute to the regulation of angiotensin II-dependant absorption processes. Intracellular positivities were also observed inside the renal vascular endothelial and proximal tubular cell in endoplasmic reticulum and nuclear envelope reflecting the synthesis and the cellular processing of ACE. The intestinal microvascular endothelium was strongly labeled suggesting that the mesenteric circulation is an important site for the production of angiotensin II. Vascular endothelial ACE was also detected in the peritubular but not glomerular capillaries of the kidney.

Catechin Contents of Foods Commonly Consumed in The Netherlands. 2. Tea, Wine, Fruit Juices, and Chocolate Milk

Article

Nov 1999

Catechins, compounds that belong to the flavonoid class, are potentially beneficial to human health. To enable an epidemiological evaluation of catechins, data on their contents in foods are required. HPLC with UV and fluorescence detection was used to determine the levels of (+)-catechin, (−)-epicatechin, (+)-gallocatechin (GC), (−)-epigallocatechin (EGC), (−)-epicatechin gallate (ECg), and (−)-epigallocatechin gallate (EGCg) in 8 types of black tea, 18 types of red and white wines, apple juice, grape juice, iced tea, beer, chocolate milk, and coffee. Tea infusions contained high levels of catechins (102−418 mg of total catechins/L), and tea was the only beverage that contained GC, EGC, ECg, and EGCg in addition to (+)-catechin and (−)-epicatechin. Catechin concentrations were still substantial in red wine (27−96 mg/L), but low to negligible amounts were found in white wine, commercially available fruit juices, iced tea, and chocolate milk. Catechins were absent from beer and coffee. The data reported he...

Evidence for health benefits of plant phenols: Local or systemic effects?

Article

Jul 2001

Peter C H Hollman

Plant phenols are mostly products of the phenylpropanoid pathway and comprise a large variety of compounds: cinnamic acids, benzoic acids, flavonoids, proanthocyanidins, stilbenes, coumarins, lignans and lignins. They are strong antioxidants and might prevent oxidative damage to biomolecules such as DNA, lipids and proteins which play a role in chronic diseases such as cancer and cardiovascular disease. Plant phenols may interfere with all stages of the cancer process, potentially resulting in a reduction of cancer risk. Only flavonols have been investigated in observational studies. Five out of seven studies showed an inverse association of flavonol intake with subsequent cardiovascular disease (CVD). A protective effect against cancer was only found in one out of four studies. Thus the epidemiological evidence does not yet allow a firm decision on the involvement of flavonols in the aetiology of either CVD or cancer. The epidemiology of flavonols points to a systemic effect. The epidemiology of tea, as a rich source of various phenols, shows inconsistent data for colon cancer, which also does not support a local effect of plant phenols. The absorption and bioavailability of plant phenols have been inadequately studied. Dietary flavonoids were thought to be poorly absorbed because of their presence as β‐glycosides (conjugates of sugars). However, conjugation with glucose enhanced human absorption. Flavonoids and other plant phenols are extensively metabolised by colonic bacteria: the ring structure is cleaved, giving a range of phenolic acids which are then absorbed. Human studies showed that only about 1% of a well‐absorbed flavonoid was excreted with an intact flavonoid backbone into urine. Major questions to be answered are whether the effective concentrations found in in vitro systems really reflect physiological concentrations. © 2001 Society of Chemical Industry

Angiotensin I converting enzyme in human intestine and kidney. Ultrastructural immunohistochemical localization

Article

Feb 1986
Histochemistry

The localization of immunoreactive angiotensin I-converting enzyme (ACE) has been investigated at the optical and ultrastructural level with anti-human ACE antibodies in the human kidney and small intestine. In both tissues ACE was found in blood vessels and in extravascular situation in the absorptive epithelial cells of intestinal mucosa and renal proximal tubules. Ultrastructural immunohistochemistry showed that in intestinal and renal proximal tubular cells ACE was prominent in microvilli and brush borders. In the kidney ACE was also present on the basolateral part of the plasmalemmal membrane, where it may contribute to the regulation of angiotensin II-dependent absorption processes. Intracellular positivities were also observed inside the renal vascular endothelial and proximal tubular cell in endoplasmic reticulum and nuclear envelope reflecting the synthesis and the cellular processing of ACE. The intestinal microvascular endothelium was strongly labeled suggesting that the mesenteric circulation is an important site for the production of angiotensin II. Vascular endothelial ACE was also detected in the peritubular but not glomerular capillaries of the kidney.

Spectrophotometric Assay and Properties of the Angiotensin-Converting Engyme of Rabbit Lung

Article

Aug 1971
BIOCHEM PHARMACOL

A sensitive, fixed-time, spectrophotometric assay for angiotensin-converting enzyme measures the rate of production of hippuric acid from hippuryl-L-histidyl-L-leucine (HHL). The angiotensin-converting enzyme from rabbit lung acetone powder extract, when assayed by this method, is optimally active at pH 8.1 to 8.3 at a chloride ion concentration of 300 mM and an HHL concentration of 5–10 mM; the Km for HHL is 2–6 mM. The enzyme was inhibited by metal-chelating agents, heavy metal salts and certain peptides. The most effective inhibitors were EDTA; CdBr2; angiotensin II; bradykinin; and a pentapeptide, L-pyroglutamyl-L-lysyl-L-tryptophyl-L-alanyl-L-proline, a component of Bothrops jararaca venom. Enzyme inhibited by 0.1 mM EDTA was completely reactivated after removal of EDTA by dialysis but, after prolonged dialysis of the enzyme against 1 mM EDTA, reactivation could only be achieved by addition of metal ions: MnCI2 (40%), ZnCl2 (100%) or Co(NO3)2 (160%). The angiotensin-converting enzyme of rabbit lung is a stable, chloride ion-activated metalloenzyme, similar to both the angiotensin-converting enzyme and kininase II of plasma.

Effect of some drugs on thromboplastin (Factor III) activity of human monocytes in vitro

Article

Feb 1980
BIOCHEM PHARMACOL

Thromboplastin activity was induced in isolated human monocytes in vitro by lectins, immune complexes, endotoxins and the ionophore A 23187. The effect of promethazine, dexamethasone, cyclic AMP analogues, indomethacin and acetylsalicylic acid on the activity increase induced by the various stimulating agents was investigated. Dexamethasone had a significant inhibitory effect on endotoxin- and lectin-induced increase of thromboplastin activity. Cyclic AMP analogues inhibited the increase induced by immune complexes and also had a small but significant inhibitory effect on the endotoxin-induced increase, Promethazine enhanced the activity induced by endotoxin and by lectins. Indomethacin and acetylsalicylic acid had no effect at the concentrations used. Cytotoxic and generally activating effects of the compounds tested were monitored by determining the release of lactate dehydrogenase, lysozyme and β-glucuronidase.

Angiotensin I converting enzyme (Kininase II) of the brush border of human and swine intestine

Article

Jul 1980
BIOCHEM PHARMACOL

Mucosal brush border of human and swine small intestine is rich in angiotensin I converting enzyme or kininase II (ACE). The brush border of the intestinal mucosa was purified by centrifugation over a discontinuous glycerol gradient. Transmission electron micrographs showed that 90 per cent of the isolated vesicles had a trilaminar membrane structure and glycocalyx, characteristic of intestinal brush border. No significant contamination by other subcellular particles was evident. In the final purified preparation, the brush border marker enzymes sucrase, trehalase and alkaline phosphatase were enriched 23-, 18- and 17-fold from human intestine and 27-, 26- and 20-fold from swine tissue. ACE was highly concentrated in the human and swine brush border. The specific activity of ACE in the human and swine brush border fractions was enriched 17- and 7.6-fold over the crude homogenate. Kininase activity was demonstrated by bioassay. Captopril, the orally active specific inhibitor of ACE, inhibited the enzyme; its I50 was 3 × 10−9. Antibody to swine kidney ACE cross-reacted with swine intestinal enzyme as shown in rocket immunoelectrophoresis, indicating that the enzymes from kidney and from intestine have common antigenic determinants and that the enzyme is concentrated on the brush border membrane. Because of the abundant presence of ACE in the intestine, interference in the functions of this enzyme may occur with chronic captopril therapy.

Sensitive method for quantitation of angiotensin I-converting enzyme (ACE) activity in tissue

Article

Oct 1995
BIOCHEM PHARMACOL

A novel sensitive and specific method for the measurement of tissue angiotensin-converting enzyme (ACE) activity utilizing HPLC is described. ACE activity was determined in detergent-extracted canine hearts utilizing the synthetic ACE-specific substrate hippuryl histidyl leucine (HHL), both in the presence and the absence of the site-specific inhibitor captopril. Tissue ACE activity was quantitated from the moles of hippuric acid (HA) formed, in time-fixed assays, utilizing HPLC separation of HA from HHL and UV-spectrophotometry for quantitation of HA as in the standard Cushman and Cheung assay (Cushman DW and Cheung HS, Biochem Pharmacol 20: 1637-1648, 1971). Separation of HA from HHL was performed by reverse phase HPLC on a phenyl silica gel column with an eluent consisting of 20% acetonitrile in 0.1 M aqueous ammonium phosphate buffer, pH 6.8. After the standard liquid/liquid extraction procedure with ethyl acetate, HPLC analysis revealed the presence of unreacted substrate, HHL, in amounts comparable to the product of interest, HA, in the final assay; moreover, the amount of HA formed did not fall completely to zero in the presence of captopril. Regional studies of canine cardiac ACE activity utilizing the HPLC-based assay and the standard assay method showed a significantly higher ACE activity in the right ventricle compared with the left ventricle (2.37 +/- 0.7 vs 1.24 +/- 0.18 mU/g, P < 0.05 [N = 6], respectively) in the HPLC-based assay, but no difference in right and left ventricular ACE activities by the standard assay (0.25 +/- 0.08 vs 0.31 +/- 0.09 mU/g [N = 6], respectively). Kinetic studies utilizing the HPLC-based assay coupled with the use of captopril showed Km (1.34 +/- 0.08 mM) and Vmax (36.8 +/- 11.5 x 10(-10) M/min) values in agreement with those in the literature. Our results demonstrate that the application of HPLC to the standard Cushman and Cheung assay improves the sensitivity and specificity of the standard assay and enables the use of much smaller amounts (approximately 4 vs approximately 400 mg for the Cushman and Cheung assay) of tissue for ACE activity assay.

Beyond alcohol: Beverage consumption and cardiovascular mortality

Article

Jul 1995
CLIN CHIM ACTA

This paper reviews epidemiological investigations which have identified an inverse relationship between alcohol consumption and death from coronary heart disease: evidence from studies of mixed populations as well as of single-sex populations have, on the whole, demonstrated that this relationship is independent of sex or age. This 'cardioprotective effect' of alcohol can be explained, at least in part, by ethanol-related increases in high density lipoprotein cholesterol and reduced platelet coagulability. With certain beverages, especially red wine, phenolic compounds may provide additional protection by altering eicosanoid metabolism in favour of increased prostacyclin and decreased thromboxane synthesis, as well as antioxidant functions which prevent the peroxidation of low-density lipoprotein. Trans-resveratrol, a tri-hydroxy stilbene present in the skins of specific grape cultivars, is a constituent of certain red wines which may play a crucial role in modulating lipoprotein metabolism, eicosanoid synthesis, oxidation and coagulation. Preliminary studies using the human hepatoma cell line HepG2 are described, demonstrating that this compound has no effect upon cell viability or overall protein synthesis in these cells, and at high concentrations DNA synthesis as measured by radioactive thymidine incorporation is enhanced. Reduced intracellular concentration and secretion of apolipoprotein B have been shown to occur in response to resveratrol although a clear dose-dependency has not yet been demonstrated. The mechanisms underlying these changes as well as the effects upon the synthesis and secretion of other apolipoproteins are under active investigation in our laboratory.

[18] Peptidyl dipeptidase A: Angiotensin I-converting enzyme

Article

Feb 1995
METHOD ENZYMOL

This chapter discusses the tissue distribution and the substrate specificity of peptidyl-dipeptidase A/angiotensin I-converting enzyme. Angiotensin I-Converting Enzyme (ACE) is a zinc metallopeptidase that belongs to the gluzincin family (clan MA) of metalloproteases of which thermolysin is the prototype. ACE cleaves the C-terminal dipeptide from angiotensin I to produce the potent vasopressor octapeptide angiotensin II and inactivates bradykinin by the sequential removal of two C-terminal dipeptides. In addition to these two main physiological substrates, which are involved in blood pressure regulation and water and salt metabolism, ACE cleaves C-terminal dipeptides from various oligopeptides with a free C-terminus. ACE is also able to cleave a C-terminal dipeptide-amide. The maximum expression of ACE occurs during the acrosome phase in murine species. ACE is exclusively produced in haploid germ cells and belongs to the group of proteins whose expression during definite maturation steps of spermiogenesis appears to be correlated with the unique process of germ cell differentiation. The inactivation of the ACE gene by homologous recombination leads to homozygous male mice with markedly reduced blood pressure, severe renal abnormalities and severely reduced fertility.

Does Wine Work

Article

Feb 1995

David M. Goldberg

(+)-Catechin Prevents Human Plasma Oxidation

Article

Mar 1998
FREE RADICAL BIO MED

Based on the recognized capacity of (+)-catechin (CTCH) to prevent free radical-mediated damage in different biological systems, its role in the protection of human plasma from oxidation was investigated. Samples of human blood plasma were incubated with 50 mM AAPH [2,2'-azobis-(2-amidinopropane) clorhidrate] or AMVN [2,2'-azobis(2,4-valeronitrile)], in the absence or the presence of CTCH (0.01 to 1 mM). Lipid oxidation was evaluated measuring the formation of 2-thiobarbituric acid reactive substances (TBARS). Alpha-tocopherol (AT), beta-carotene (BC), and CTCH were measured by reverse phase HPLC with electrochemical detection. TBARS formation was dependent on incubation time and on the nature of the azocompound, yielding 4.8 +/- 0.9, and 14.9 +/- 3.4 microM MDA, after 4 h, in AAPH and AMVN-exposed plasma, respectively. Plasma AT and BC were extensively depleted under these oxidant conditions. The addition of CTCH prevented or delayed the formation of TBARS, and the depletion of AT and BC in a dose dependent manner. This antioxidant effect was dependent on the concentration of CTCH and on the physical characteristics of the radical initiator. CTCH supplementation modified not only the lag time for the antioxidants depletion, but also the consumption rate. These results indicate that CTCH was an effective antioxidant in human blood plasma, delaying the consumption of endogenous lipid soluble antioxidants (AT and BC) and inhibiting lipid oxidation.

Levels of flavan-3-ols in French wines

Article

Nov 1999

French wines are abundant sources of phenolic compounds. The content of several catechins, i.e., (+)-catechin, (-)-epicatechin, dimers B1, B2, B3, and B4, trimers C1, and trimer 2 (T2), of 160 French wines was determined by HPLC with UV detection. Red wines (n = 95) were found to have high levels of catechins, ranging from 32.8 to 209.8 mg/L (mean concentration 114.5 mg/L) for (+)-catechin, from 22.1 to 130.7 mg/L (mean concentration 75.7 mg/L) for (-)-epicatechin, from 7.8 to 39.1 mg/L (mean concentration 25.4 mg/L) for B1, from 18.3 to 93 mg/L (mean concentration 47.4 mg/L) for B2, from 21.4 to 215.6 mg/L (mean concentration 119.6 mg/L) for B3, from 20.2 to 107.2 mg/L (mean concentration 81.9 mg/l) for B4, from 8.6 to 36.9 mg/L (mean concentration 26.3 mg/L) for C1, and from 26.7 to 79.3 mg/L (mean concentration 67.1 mg/L) for T2. White and rosé wines (n = 57 and n = 8) were found to have low levels of (+)-catechin (mean concentrations 9.8 and 10.6 mg/L, respectively) and (-)-epicatechin (mean concentrations 5.3 and 6.5 mg/L, respectively). These data provide a basis for the epidemiological evaluation of catechin intake by the consumption of French wine.

Liquid chromatographic determination of hippuric acid for the evaluation of ethacrynic acid as angiotensin converting enzyme inhibitor

Article

Jun 1999
J PHARMACEUT BIOMED

A rapid, simple and interference-free method is described to evaluate the inhibitory effects of organic compounds on the activity of angiotensin converting enzyme irrespective of their acid-base properties. The assay is based on the high performance liquid chromatographic separation of the synthetic substrate hippuryl-L-histidyl-L-leucine, the hydrolysis product hippuric acid and the test compound. Using the new method, the diuretic drug ethacrynic acid was found to act as an inhibitor for the enzyme in a non competitive mode.

Catechin Contents of Foods Commonly Consumed in The Netherlands. 2. Tea, Wine, Fruit Juices, and Chocolate Milk

Article

Jun 2000

Catechins, compounds that belong to the flavonoid class, are potentially beneficial to human health. To enable an epidemiological evaluation of catechins, data on their contents in foods are required. HPLC with UV and fluorescence detection was used to determine the levels of (+)-catechin, (-)-epicatechin, (+)-gallocatechin (GC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECg), and (-)-epigallocatechin gallate (EGCg) in 8 types of black tea, 18 types of red and white wines, apple juice, grape juice, iced tea, beer, chocolate milk, and coffee. Tea infusions contained high levels of catechins (102-418 mg of total catechins/L), and tea was the only beverage that contained GC, EGC, ECg, and EGCg in addition to (+)-catechin and (-)-epicatechin. Catechin concentrations were still substantial in red wine (27-96 mg/L), but low to negligible amounts were found in white wine, commercially available fruit juices, iced tea, and chocolate milk. Catechins were absent from beer and coffee. The data reported here provide a base for the epidemiological evaluation of the effect of catechins on the risk for chronic diseases.

Procyanidin Content and Variation in Some Commonly Consumed Foods

Article

Sep 2000

Procyanidins are a subclass of flavonoids found in commonly consumed foods that have attracted increasing attention due to their potential health benefits. However, little is known regarding their dietary intake levels because detailed quantitative information on the procyanidin profiles present in many food products is lacking. Therefore, the procyanidin content of red wine, chocolate, cranberry juice and four varieties of apples has been determined. On average, chocolate and apples contained the largest procyanidin content per serving (164.7 and 147.1 mg, respectively) compared with red wine and cranberry juice (22.0 and 31.9 mg, respectively). However, the procyanidin content varied greatly between apple samples (12.3-252.4 mg/serving) with the highest amounts on average observed for the Red Delicious (207.7 mg/serving) and Granny Smith (183.3 mg/serving) varieties and the lowest amounts in the Golden Delicious (92.5 mg/serving) and McIntosh (105.0 mg/serving) varieties. The compositional data reported herein are important for the initial understanding of which foods contribute most to the dietary intake of procyanidins and may be used to compile a database necessary to infer epidemiological relationships to health and disease.

Plant-derived phenolic antioxidants

Article

Dec 2000

Antioxidant nutrients are important for limiting damaging oxidative reactions in cells, which may predispose to the development of major clinical conditions such as heart disease and cancer. There is great interest in the possibility that the antioxidant potential of plant-derived phenolic compounds, such as flavonoids, may reduce the risk of developing these conditions. Antioxidant effectiveness in vivo depends on the bioavailability of these compounds, which was assumed to be low. However, recent studies with improved methodology indicate that some plant phenolics appear in plasma and body tissues and, thus, may be important nutritional antioxidants. However, this cannot be established with certainty until their effects on biomarkers of oxidative stress are established.

Quantitative Analysis of Flavan-3-ols in Spanish Foodstuffs and Beverages

Article

Dec 2000

An HPLC method, using detection after postcolumn derivatization with p-dimethylaminocynnamaldehyde (DMACA), was developed for the quantitative analysis of individual flavanols in food. This method was applied to flavanol determination in 56 different kinds of Spanish food products, including fruit, vegetables, legumes, beverages (cider, coffee, beer, tea, and wine), and chocolate. The determined compounds corresponded to the catechins and proanthocyanidin dimers and trimers usually present in food and, therefore, they were representative of the flavanols of low degree of polymerization consumed with the diet. The data generated could be used for calculation of the dietary intake of either individual or total flavanols, which would allow the further establishment of epidemiological correlations with the incidence of chronic diseases. Similar flavanol profiles were found in the different samples of a similar type of product, even though important variations could exist in the concentrations of total and individual flavanols among them. This was attributed to factors such as sample origin, stage of ripeness, post-harvesting conservation, and processing. Total flavanol contents varied from nondetectable in most of the vegetables to 184 mg/100 g found in a sample of broad bean. Substantial amounts were also found in some fruits, such as plum and apple, as well as in tea and red wine. Epicatechin was the most abundant flavanol, followed by catechin and procyanidin B2. In general, catechins were found in all the flavanol-containing products, but the presence of gallocatechins was only relevant in pomegranate, broad bean, lentil, grape, wine, beer, and tea, and most of the berries. Galloyled flavanols were only detected in strawberry, medlar, grape, and tea.

Short- and Long-Term Black Tea Consumption Reverses Endothelial Dysfunction in Patients With Coronary Artery Disease

Article

Aug 2001
CIRCULATION

Background: Epidemiological studies suggest that tea consumption decreases cardiovascular risk, but the mechanisms of benefit remain undefined. Endothelial dysfunction has been associated with coronary artery disease and increased oxidative stress. Some antioxidants have been shown to reverse endothelial dysfunction, and tea contains antioxidant flavonoids. Methods and Results-- To test the hypothesis that tea consumption will reverse endothelial dysfunction, we randomized 66 patients with proven coronary artery disease to consume black tea and water in a crossover design. Short-term effects were examined 2 hours after consumption of 450 mL tea or water. Long-term effects were examined after consumption of 900 mL tea or water daily for 4 weeks. Vasomotor function of the brachial artery was examined at baseline and after each intervention with vascular ultrasound. Fifty patients completed the protocol and had technically suitable ultrasound measurements. Both short- and long-term tea consumption improved endothelium- dependent flow-mediated dilation of the brachial artery, whereas consumption of water had no effect (P<0.001 by repeated-measures ANOVA). Tea consumption had no effect on endothelium-independent nitroglycerin-induced dilation. An equivalent oral dose of caffeine (200 mg) had no short-term effect on flow-mediated dilation. Plasma flavonoids increased after short- and long-term tea consumption. Conclusions: Short- and long-term black tea consumption reverses endothelial vasomotor dysfunction in patients with coronary artery disease. This finding may partly explain the association between tea intake and decreased cardiovascular disease events.

Wine Polyphenols Decrease Blood Pressure, Improve NO Vasodilatation, and Induce Gene Expression

Article

Sep 2001
Hypertension

The effects of short-term oral administration of red wine polyphenolic compounds on hemodynamic parameters and on vascular reactivity were investigated in rats. Endothelial function and vascular smooth muscle contractility were studied in association with the induction of gene expression in the vascular wall. Rats were treated daily for 7 days by intragastric administration of either 5% glucose or red wine polyphenolic compounds (20 mg/kg). Administration of these compounds produced a progressive decrease in systolic blood pressure, which became significantly different on day 4. Aortas from rats treated with red wine polyphenolic compounds displayed increased endothelium-dependent relaxation to acetylcholine that was related to increased endothelial NO activity and involved a mechanism sensitive to superoxide anion scavengers. However, no increase in whole-body oxidative stress has been observed in rats treated with red wine polyphenolic compounds, as shown by plasma glutathione assay. Also, in the aorta, red wine polyphenolic compounds increased the expression of cyclooxygenase-2 and increased the release of endothelial thromboxane A(2), which compensated for the extraendothelial NO-induced hyporeactivity in response to norepinephrine, resulting from enhanced inducible NO synthase expression. The present study provides evidence that short-term oral administration of red wine polyphenolic compounds produces a decrease in blood pressure in normotensive rats. This hemodynamic effect was associated with an enhanced endothelium-dependent relaxation and an induction of gene expression (of inducible NO synthase and cyclooxygenase-2) within the arterial wall, which together maintain unchanged agonist-induced contractility. These effects of red wine polyphenolic compounds may be a potential mechanism for preventing cardiovascular diseases.

Extraction of Phenolics and Changes in Antioxidant Activity of Red Wines during Vinification

Article

Jan 2002

The moderate consumption of alcoholic beverages has been associated with protection against the development of coronary heart disease. Although alcohol itself can help prevent coronary heart disease through a number of mechanisms, red wine appears to offer protection above and beyond that attributable to alcohol alone. Red wine is a complex fluid containing grape, yeast, and wood-derived phenolic compounds, the majority of which have been recognized as potent antioxidants. The aim of this study was to investigate the major phenolic contributors to the antioxidant activity of wine. To this end, four wines were followed during the first 7-9 days of vinification. Individual phenolic compounds were quantified by HPLC, and antioxidant activity was determined by electron spin resonance spectroscopy. The extraction of the phenolics was found to be influenced by vinification procedure, grape quality, and grape variety. Although fermenting wines reached a total phenolic content comparable to that of a bottled wine after 9 days of vinification, the antioxidant activity was significantly lower than that of a finished wine. This suggests that the larger polyphenolic complexes and condensation products that appear during aging make a sizable contribution to the overall antioxidant activity of red wines.

Evidence that the antioxidant flavonoids in tea and cocoa are beneficial for cardiovascular health

Article

Mar 2002

Epidemiologic studies suggest an inverse association of tea consumption with cardiovascular disease. The antioxidant effects of flavonoids in tea (including preventing oxidative damage to LDL) are among the potential mechanisms that could underlie the protective effects. Other possible mechanisms include attenuating the inflammatory process in atherosclerosis, reducing thrombosis, promoting normal endothelial function, and blocking expression of cellular adhesion molecules. Cocoa and chocolate can also be rich sources of flavonoids. Flavanols and procyanidins isolated from cocoa exhibit strong antioxidant properties in-vitro. In acute feeding studies, flavanol-rich cocoa and chocolate increased plasma antioxidant capacity and reduced platelet reactivity. Based on limited data, approximately 150 mg of flavonoids is needed to trigger a rapid antioxidant effect and changes in prostacyclin. Some dose-response evidence demonstrates an antioxidant effect with approximately 500 mg flavonoids. Brewed tea typically contains approximately 172 mg total flavonoids per 235 ml (brewed for 2 min); hence, consumption of 1 and 3.5 cups of tea would be expected to elicit acute and chronic physiologic effects, respectively. Chocolate is more variable with some products containing essentially no flavonoids (0.09 mg procyanidin/g), whereas others are high in flavonoids (4 mg procyanidin/g). Thus, approximate estimates of flavonoid rich chocolate needed to exert acute and chronic effects are 38 and 125 g, respectively. Collectively, the antioxidant effects of flavonoid-rich foods may reduce cardiovascular disease risk.

Tea Flavonoids: Bioavailability In Vivo and Effects on Cell Signaling Pathways In Vitro

Article

Jan 2002

The elucidation of the potential health benefits of tea beverage continues to be a focus of research in many laboratories. Beneficial effects of tea have been particularly evident in animal tumorigenesis models, with green and black tea frequently demonstrating similar effectivity. Human data are now emerging to support a beneficial role for tea in cardiovascular disease, but the data with respect to cancer risk at various sites remain inconclusive. The constituent flavonoids of green and black tea beverage are known to be potent antioxidants, and although this may be a major factor in explaining their biological activity, it appears that the gallated flavonoids in particular (e.g., epigallocatechin gallate and the gallated theaflavins) impact on a wide range of molecular targets that influence cell growth and more specifically pathways such as those involving angiogenesis. Data on the pharmacokinetic properties of tea flavonoids, primarily on the catechins and therefore related most closely to green tea, have provided indications of the plasma levels and circulating molecular forms that may be expected in humans following tea consumption. The structural complexity of black tea flavonoids, in particular the thearubigins, has hindered efforts to describe their bioavailability and to perform mechanistic studies. Recent studies on the effects of catechins and theaflavins on growth factor-, nuclear factor-kappaB-, and stress-mediated signal transductions are described in this review, where possible in relation to their bioavailability in vivo. These studies indicate that effects that may be relevant to both cancer and atherosclerosis are often observed at tea flavonoid levels that could realistically be encountered in vivo. However, more studies need to be performed using those molecular forms of tea flavonoids (methylated, sulfated, and glucuronidated conjugates) that are the major circulating species encountered following tea consumption. Such studies, combined with further human epidemiological and interventional data, should ultimately elucidate the full beneficial potential of tea beverage on human health.

Study of Catechin and Xanthine Tea Profiles as Geographical Tracers

Article

Apr 2002

The contents of gallic acid, epigallocatechin gallate, epigallocatechin, epicatechin, epicatechin gallate, catechin, caffeine, theophylline, and theobromine were determined in a set of 45 tea samples, including fermented (black and red) and nonfermented (green) teas of different geographical origins (i.e., China, Japan, Kenya, Sri Lanka, and India). A reversed-phase high performance liquid chromatographic method with gradient elution and photometric detection at 275 nm was used to carry out the analysis. Before the HPLC determination, an extraction step was developed using a mixture of acetonitrile and water (60:40, v/v). Pattern recognition techniques involving principal component analysis (PCA) and linear discriminant analysis (LDA) were applied to differentiate the tea samples according to their geographical origins. Catechins, gallic acid, and tea alkaloids are adequate chemical descriptors to distinguish between fermented and nonfermented tea samples cultivated in different geographical areas.

Vascular and cardiac benefits of angiotensin receptor blockers

Article

Nov 2002
AM J MED

Ernesto L. Schiffrin

Angiotensin II not only is a vasoconstrictor, but it also affects cell growth and apoptosis, inflammation, fibrosis, and coagulation. Blockade of the renin-angiotensin system, either with inhibitors of the generation of angiotensin (angiotensin-converting enzyme [ACE] inhibitors) or with blockers of angiotensin receptors, reduces blood pressure and inhibits other pathophysiological actions. These other effects provide benefits in coronary heart disease, heart failure, diabetic nephropathy, and stroke beyond blood pressure reduction. These benefits were first demonstrated with ACE inhibitors. However, the mechanism of action of angiotensin receptor blockers, which block angiotensin II stimulation at the angiotensin type 1 receptor but not at the type 2 receptor, may have advantages, particularly for endothelial dysfunction and vascular remodeling, as well as cardiac and renal protection. Recent multicenter trials suggest that ACE inhibitors and angiotensin receptor blockers may reduce morbidity and mortality associated with cardiovascular and renal disease beyond blood pressure reduction. Several studies with different angiotensin receptor blockers, including comparisons with ACE inhibitors, are under way, and should provide further guidance for their clinical use.

Flavan-3-ols and procyanidins protect liposomes against lipid oxidation and disruption of the bilayer

Article

Feb 2003
FREE RADICAL BIO MED

The antioxidant activity and the membrane effects of the flavanols (-)-epicatechin, (+)-catechin, and their related oligomers, the procyanidins, were evaluated in liposomes composed by phosphatidylcholine:phosphatidylserine (60:40, molar ratio). When liposomes were oxidized with a steady source of free radicals, the flavanols and procyanidins (25 microM monomer equivalents) inhibited oxidation in a manner that was related to procyanidin chain length. Flavanols and procyanidins did not influence membrane fluidity or lipid lateral phase separation. However, flavanols and procyanidins induced a decrease in the membrane surface potential and protected membranes from detergent-induced disruption. These effects were dependent on flavonoid concentration, procyanidin chain length, and membrane composition. Flavanol- and procyanidin-induced inhibition of lipid oxidation was correlated with their effect on membrane surface potential and integrity. These results indicate that the interaction of flavanols and procyanidins with phospholipid head groups, particularly with those containing hydroxyl groups, is associated with a reduced rate of membrane lipid oxidation. Thus, flavanols and procyanidins can potentially reduce oxidative modifications of membranes by restraining the access of oxidants to the bilayer and the propagation of lipid oxidation in the hydrophobic membrane matrix.

Determination of Tea Components with Antioxidant Activity

Article

Aug 2003

Levels of essential elements with antioxidant activity, as well as catechins, gallic acid, and caffeine levels, in a total of 45 samples of different teas commercialized in Spain have been evaluated. Chromium, manganese, selenium, and zinc were determined in the samples mineralized with HNO(3) and V(2)O(5), using ETAAS as the analytical technique. The reliability of the procedure was checked by analysis of a certified reference material. Large variations in the trace element composition of teas were observed. The levels ranged from 50.6 to 371.4 ng/g for Cr, from 76.1 to 987.6 microg/g for Mn, from 48.5 to 114.6 ng/g for Se, and from 56.3 to 78.6 ng/g for Zn. The four major catechins [(-)-epigallocatechin gallate (EGCG), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), and (-)-epicatechin (EC)], gallic acid (GA), and caffeine were simultaneously determined by a simple and fast HPLC method using a photodiode array detector. In all analyzed samples, EGCG ranged from 1.4 to 103.5 mg/g, EGC from 3.9 to 45.3 mg/g, ECG from 0.2 to 45.6 mg/g, and EC ranged from 0.6 to 21.2 mg/g. These results indicated that green tea has a higher content of catechins than both oolong and fermented teas (red and black teas); the fermentation process during tea manufacturing reduces the levels of catechins significantly. Gallic acid content ranged from 0.039 to 6.7 mg/g; the fermentation process also elevated remarkably gallic acid levels in black teas (mean level of 3.9 +/- 1.5 mg/g). The amount of caffeine in the analyzed samples ranged from 7.5 to 86.6 mg/g, and the lower values were detected in green and oolong teas. This study will be useful for the appraisal of trace elements and antioxidant components in various teas, and it will also be of interest for people who like drinking this beverage.

Cocoa Has More Phenolic Phytochemicals and a Higher Antioxidant Capacity than Teas and Red Wine

Article

Dec 2003

Black tea, green tea, red wine, and cocoa are high in phenolic phytochemicals, among which theaflavin, epigallocatechin gallate, resveratrol, and procyanidin, respectively, have been extensively investigated due to their possible role as chemopreventive agents based on their antioxidant capacities. The present study compared the phenolic and flavonoid contents and total antioxidant capacities of cocoa, black tea, green tea, and red wine. Cocoa contained much higher levels of total phenolics (611 mg of gallic acid equivalents, GAE) and flavonoids (564 mg of epicatechin equivalents, ECE) per serving than black tea (124 mg of GAE and 34 mg of ECE, respectively), green tea (165 mg of GAE and 47 mg of ECE), and red wine (340 mg of GAE and 163 mg of ECE). Total antioxidant activities were measured using the 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays and are expressed as vitamin C equivalent antioxidant capacities (VCEACs). Cocoa exhibited the highest antioxidant activity among the samples in ABTS and DPPH assays, with VCEACs of 1128 and 836 mg/serving, respectively. The relative total antioxidant capacities of the samples in both assays were as follows in decreasing order: cocoa > red wine > green tea > black tea. The total antioxidant capacities from ABTS and DPPH assays were highly correlated with phenolic content (r2 = 0.981 and 0.967, respectively) and flavonoid content (r2 = 0.949 and 0.915). These results suggest that cocoa is more beneficial to health than teas and red wine in terms of its higher antioxidant capacity.

Inhibition of Angiotensin Converting Enzyme Activity by Flavanol-Rich Foods

Abstract

No full-text available

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