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Chemopreventive and anticancer activity of flavonoids and its possibility for clinical use by combining with conventional chemotherapeutic agents.
Kikuchi, H, Yuan, B, Hu, X, Okazaki, M
American journal of cancer research. 2019;9(8):1517-1535
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Novel therapies for cancer treatment using herbs and edible components of plants are continuously being studied as an adjunct to conventional cancer therapies: antitumor drugs and radiation. Resistance to drugs, and tumour recurrence rates suggest that new therapies are needed. This 2019 review discusses the possible strategy of combining flavonoids, nutraceuticals and conventional chemotherapeutic agents to minimise adverse effects, and improve quality of life of patients undergoing traditional treatments. Flavonoids, such as EGCG, Quercetin, Luteolin, Glabridin and Naringin demonstrate several clinically interesting mechanisms: anti-angiogenic and anti-metastatic properties, apoptosis and autophagy promoting activities, and immunomodulatory effects. On the downside there are questions over the low bioavailability of flavonoids from foods. The widely accepted consensus is that combination treatments which embrace novel therapies alongside traditional treatment are clinically safe. The interest in flavonoids is principally for improving chemotherapy sensitivity and minimizing the adverse side effects of these treatments. The molecular mechanisms underlying flavonoids multiple pharmacological effects make them a potential adjunctive agent for cancer chemoprevention although more clinical trials are needed.
Abstract
Cancer is a diverse class of diseases characterized by uncontrolled cell growth with the potential to invade and spread to other parts of the body, and continues to be one of the leading causes of death worldwide. Conventional cancer treatment modalities include antitumor drugs, surgical resection, locally targeted therapies such as radiation therapy. Along with improved understanding of the molecular pathogenesis of various cancers, generation and the use of smart targeted anti-cancer drugs have been challenged. The need for novel therapeutic strategies remains paramount given the sustained development of drug resistance, tumor recurrence, and metastasis. Development of new strategies aimed at improving chemotherapy sensitivity and minimizing the adverse side effects is thus essential for obtaining satisfied therapeutic outcomes for patients and enhancing their quality of life. Emerging evidence has reported that many cancer patients use either herbs employed in complementary therapies or dietary agents that influence cellular signaling worldwide. Numerous components of edible plants, collectively termed phytochemicals that have beneficial effects for health, are being reported increasingly in the scientific literature. Of those, flavonoids have attracted much attention by virtue of its wide variety of biological functions including antioxidant, anti-inflammatory, and anticancer activity. In this review, we highlight the molecular mechanisms underlying its multiple pharmacological effects, especially focusing on cancer chemoprevention. We further discuss possible strategies to develop anticancer therapy by combining flavonoids nutraceuticals and conventional chemotherapeutic agents. We also highlight numerous pharmacokinetic challenges such as bioavailability, drug-drug interactions, which are still fundamental questions concerning its future clinical application.
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Potential Factors Influencing the Effects of Anthocyanins on Blood Pressure Regulation in Humans: A Review.
Vendrame, S, Klimis-Zacas, D
Nutrients. 2019;11(6)
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Anthocyanins (ACNs) are plant compounds belonging to the flavonoid group of polyphenols and are naturally occurring in a number of foods. They are responsible for the red, blue and purple pigmentation within plant foods, such as blueberries and raspberries and are known to contain therapeutic compounds. Several studies have investigated the anti-inflammatory, antioxidant and blood pressure modulation properties within ACNs, however, results for blood pressure modulation, unlike those for anti-inflammatory and antioxidant properties have been mixed and less consistent. This paper reviews 66 human intervention trials exploring the effects of various forms of ACNs, like whole berries, concentrates and freeze-dried powders in order to identify the singular variables related to blood pressure modulation in order to further investigate. Having looked at a number of variables within the trials, researchers concluded that ACNs do in fact contain blood pressure lowering properties, but further research into varying factors including dose effect, synergistic effects, absorption and metabolism and the functionality of the individuals gut microbiota is needed to clarify results further.
Abstract
Dietary intake of anthocyanins (ACNs) is associated with a reduced risk of cardiovascular and coronary heart disease. While the anti-inflammatory, antioxidant, and lipid-lowering effects of ACN consumption have been consistently reported, their effect(s) on blood pressure regulation is less consistent and results from human studies are mixed. The objective of this review is attempting to identify potential patterns which may explain the variability in results related to blood pressure. To do so, we review 66 human intervention trials testing the effects on blood pressure of purified ACN or ACN-rich extracts, or whole berries, berry juices, powders, purees and whole phenolic extracts, from berries that are rich in ACN and have ACNs as predominant bioactives. Several factors appear to be involved on the mixed results reported. In particular, the baseline characteristics of the population in terms of blood pressure and total flavonoid intake, the dose and duration of the intervention, the differential effects of individual ACN and their synergistic effects with other phytochemicals, the ACN content and bioavailability from the food matrix, and individual differences in ACN absorption and metabolism related to genotype and microbiota enterotypes.
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Dietary phytochemicals in breast cancer research: anticancer effects and potential utility for effective chemoprevention.
Kapinova, A, Kubatka, P, Golubnitschaja, O, Kello, M, Zubor, P, Solar, P, Pec, M
Environmental health and preventive medicine. 2018;23(1):36
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Bioactive phytochemicals are continually being studied for their role in cancer prevention with increasing evidence for flavonoids, carotenoids, phenolic acids, and organosulfur compounds (found in cruciferous vegetables). This 2018 review explores the protective effects of a broad spectrum of plant-derived substances. In total, more than 5000 individual phytochemicals have been identified in plant-derived foods, such as fruits, vegetables, and grains. These bioactive compounds have been shown to have antitumor activity, reduce inflammation, induce apoptosis (cell death), inhibit the proliferation of aggressive tumour cells, and impact on metastasis (migration of cancer cells). Specifically, in breast cancer, a few studies have examined phytochemicals on cancer stem cells (the originating tumour cells) and found that curcumin, genistein, indol-3-carbinol, c-phycocyanin, resveratrol, and quercetin downregulated their activity. Systematic reviews of dietary patterns and breast cancer show vegetables, and especially fibre, to be consistently protective against reduced risk of mammary carcinogenesis. Dietary polyphenols are considered a cost-effective approach to cancer care however there is still a lack of evidence due to the complex nature of combined phytochemicals versus isolated agents. Wholefood consumption is considered to improve bioavailability compared to supplementation however phytochemicals are a low-dose component of foods. There is also concern that some phytochemicals may act as carcinogens or tumour promoters (for example, beta-carotene). More clinical trials are required to fully understand phytochemicals and breast cancer care.
Abstract
Cancerous tissue transformation developing usually over years or even decades of life is a highly complex process involving strong stressors damaging DNA, chronic inflammation, comprehensive interaction between relevant molecular pathways, and cellular cross-talk within the neighboring tissues. Only the minor part of all cancer cases are caused by inborn predisposition; the absolute majority carry a sporadic character based on modifiable risk factors which play a central role in cancer prevention. Amongst most promising candidates for dietary supplements are bioactive phytochemicals demonstrating strong anticancer effects. Abundant evidence has been collected for beneficial effects of flavonoids, carotenoids, phenolic acids, and organosulfur compounds affecting a number of cancer-related pathways. Phytochemicals may positively affect processes of cell signaling, cell cycle regulation, oxidative stress response, and inflammation. They can modulate non-coding RNAs, upregulate tumor suppressive miRNAs, and downregulate oncogenic miRNAs that synergically inhibits cancer cell growth and cancer stem cell self-renewal. Potential clinical utility of the phytochemicals is discussed providing examples for chemoprevention against and therapy for human breast cancer. Expert recommendations are provided in the context of preventive medicine.
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Spices and Atherosclerosis.
Tsui, PF, Lin, CS, Ho, LJ, Lai, JH
Nutrients. 2018;10(11)
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Cardiovascular disease (CVD) is one of the leading causes of death and disability in the world. Atherosclerosis, characterised by the accumulation of fat and inflammation in blood vessels, is the main feature of CVD. Common spices such as pepper, ginger, garlic, onion, cinnamon and chilli may have effects on the initiation and development of atherosclerosis. In this review, the authors focused on the potential protective effects of spices, in atherosclerosis and CVD. Most studies to date have been carried out either in cell culture or in animals. These have revealed various potential mechanisms by which spices exert their beneficial effects, including anti-oxidant, anti-atherogenic, anti-coagulant, anti-inflammatory and cholesterol-lowering properties. There are some human studies evaluating the effects of spices on high blood pressure. Although saffron, turmeric, and chilli pepper had no effect on blood pressure, cinnamon demonstrated significant blood pressure lowering effects in patients with diabetes. Garlic has been shown to have the potential to reduce blood pressure in patients with high blood pressure. These studies provide information on the beneficial roles of spices in reducing cardiovascular risk factors. The types of spices consumed vary across cultures, and currently there are no available population studies showing that consumption of spices is associated with reduction of CVD nor any recommendations for the amounts of spices to be consumed. The authors conclude that the consumption of spices should be encouraged across countries to promote good health.
Abstract
Cardiovascular disease is one of the leading causes of death and disability in the world. Atherosclerosis, characterized by lipid accumulation and chronic inflammation in the vessel wall, is the main feature of cardiovascular disease. Although the amounts of fruits and vegetables present in the diets vary by country, diets, worldwide, contain large amounts of spices; this may have positive or negative effects on the initiation and development of atherosclerosis. In this review, we focused on the potential protective effects of specific nutrients from spices, such as pepper, ginger, garlic, onion, cinnamon and chili, in atherosclerosis and atherosclerotic cardiovascular disease. The mechanisms, epidemiological analysis, and clinical studies focusing on a variety of spices are covered in this review. Based on the integrated information, we aimed to raise specific recommendations for people with different dietary styles for the prevention of atherosclerotic cardiovascular disease through dietary habit adjustments.
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Could gestational diabetes mellitus be managed through dietary bioactive compounds? Current knowledge and future perspectives.
Santangelo, C, Zicari, A, Mandosi, E, Scazzocchio, B, Mari, E, Morano, S, Masella, R
The British journal of nutrition. 2016;115(7):1129-44
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Gestational diabetes mellitus (GDM) is the most common metabolic disorder during pregnancy. Women with GDM are at a high risk of developing type 2 diabetes (T2D) later in life. Moreover, uncontrolled GDM is linked with a detrimental intra-uterine environment, which leads to foetal complications and an increased risk for the child of developing obesity and metabolic disorders. The aim of the review is to examine the current knowledge and issues about the impact of dietary polyphenols on the mechanisms and/or factors regulating glucose homeostasis, inflammation and adipose tissue function in metabolic alterations linked with GDM. Moreover, this study also reviews the role of Omega-3 fatty acids in pregnancy. The study is a descriptive review based on several studies. Literature data is mainly derived from in vitro and animal models. In vitro and animal studies show that almost all subclasses of flavonoids, stilbene RSV and some olive oil phenolic compounds, interact and modulate several molecular pathways regulating insulin. Obesity worsens GDM with increased risk of developing metabolic disorders in both mother and offspring later in life. The adoption of healthy lifestyle, with adherence to a healthy dietary pattern, has positive effects on the prevention and management of diabetes.
Abstract
Gestational diabetes mellitus (GDM) is a serious problem growing worldwide that needs to be addressed with urgency in consideration of the resulting severe complications for both mother and fetus. Growing evidence indicates that a healthy diet rich in fruit, vegetables, nuts, extra-virgin olive oil and fish has beneficial effects in both the prevention and management of several human diseases and metabolic disorders. In this review, we discuss the latest data concerning the effects of dietary bioactive compounds such as polyphenols and PUFA on the molecular mechanisms regulating glucose homoeostasis. Several studies, mostly based on in vitro and animal models, indicate that dietary polyphenols, mainly flavonoids, positively modulate the insulin signalling pathway by attenuating hyperglycaemia and insulin resistance, reducing inflammatory adipokines, and modifying microRNA (miRNA) profiles. Very few data about the influence of dietary exposure on GDM outcomes are available, although this approach deserves careful consideration. Further investigation, which includes exploring the 'omics' world, is needed to better understand the complex interaction between dietary compounds and GDM.
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Effect of Flavonoids on Upper Respiratory Tract Infections and Immune Function: A Systematic Review and Meta-Analysis.
Somerville, VS, Braakhuis, AJ, Hopkins, WG
Advances in nutrition (Bethesda, Md.). 2016;7(3):488-97
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Upper respiratory tract infections (URTIs) are common and include sinusitis, tonsillitis, pharyngitis, otitis media, laryngitis, and the “common cold”. More than 90% of URTIs are cause by viruses. Flavonoids are found in many plant foods and have a range of physiologic effects in humans, including antiviral, anti-inflammatory, cytotoxic, antimicrobial, and antioxidant. The purpose of this systematic review and meta-analysis of 14 randomised controlled trials was to investigate the efficacy of flavonoids on URTIs and immune function. The authors found that flavonoids decrease URTI incidence by 33% compared with controls with no increase in adverse effects. There was also a non-significant decrease in URTI severity and duration with the flavonoid intervention. The meta-analysis demonstrated that differences between flavonoids and control for all immune biomarkers were clinically irrelevant. The authors therefore suggest that flavonoids do not attenuate URTI incidence by altering immune function but by an antiviral mechanism. They call for further research to establish the optimal dose and type of flavonoids.
Abstract
Previous research on animals indicates flavonoid compounds have immunomodulatory properties; however, human research remains inconclusive. The aim of this systematic review was to assess the efficacy of dietary flavonoids on upper respiratory tract infections (URTIs) and immune function in healthy adults. A created search strategy was run against Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and EMBASE classic, CINAHL, and AMED. The returned studies were initially screened, and 2 reviewers independently assessed the remaining studies for eligibility against prespecified criteria. Fourteen studies, of 387 initially identified, were included in this review, and the primary outcome measure was the effect of flavonoids on URTI incidence, duration, and severity. Of the included studies, flavonoid supplementation ranged from 0.2 to 1.2 g/d. Overall, flavonoid supplementation decreased URTI incidence by 33% (95% CI: 31%, 36%) compared with control, with no apparent adverse effects. Sick-day count was decreased by 40% with flavonoid supplementation, although unclear. Differences in bio-immune markers (e.g., interleukin-6, tumor necrosis factor-α, interferon-γ, neutrophils) were trivial between the intervention and control groups during the intervention and after exercise when a postintervention exercise bout was included. These findings suggest that flavonoids are a viable supplement to decrease URTI incidence in an otherwise healthy population.