Flavonoids, a group of natural substances with variable phenolic structures, are found in fruits, vegetables, grains, bark, roots, stems, flowers, tea and wine. These natural products are well known for their beneficial effects on health and efforts are being made to isolate the ingredients so called flavonoids. Flavonoids are now considered as an indispensable component in a variety of nutraceutical, pharmaceutical, medicinal and cosmetic applications. This is attributed to their anti-oxidative, anti-inflammatory, anti-mutagenic and anti-carcinogenic properties coupled with their capacity to modulate key cellular enzyme function. Research on flavonoids received an added impulse with the discovery of the low cardiovascular mortality rate and also prevention of CHD. Information on the working mechanisms of flavonoids is still not understood properly. However, it has widely been known for centuries that derivatives of plant origin possess a broad spectrum of biological activity. Current trends of research and development activities on flavonoids relate to isolation, identification, characterisation and functions of flavonoids and finally their applications on health benefits. Molecular docking and knowledge of bioinformatics are also being used to predict potential applications and manufacturing by industry. In the present review, attempts have been made to discuss the current trends of research and development on flavonoids, working mechanisms of flavonoids, flavonoid functions and applications, prediction of flavonoids as potential drugs in preventing chronic diseases and future research directions.

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Flavonoids: an overview

https://jeffreydachmd.com/wp-content/uploads/2015/01/Molecular-targets-of-dietary-agents-prevention-cancer-aggarwal-2006.pdf

Molecular targets of dietary agents for prevention and therapy of cancer

Polyphenols, including flavonoids, phenolic acids, proanthocyanidins and resveratrol, are a large and heterogeneous group of phytochemicals in plant-based foods, such as tea, coffee, wine, cocoa, cereal grains, soy, fruits and berries. Growing evidence indicates that various dietary polyphenols may influence carbohydrate metabolism at many levels. In animal models and a limited number of human studies carried out so far, polyphenols and foods or beverages rich in polyphenols have attenuated postprandial glycemic responses and fasting hyperglycemia, and improved acute insulin secretion and insulin sensitivity. The possible mechanisms include inhibition of carbohydrate digestion and glucose absorption in the intestine, stimulation of insulin secretion from the pancreatic β–cells, modulation of glucose release from the liver, activation of insulin receptors and glucose uptake in the insulin-sensitive tissues, and modulation of intracellular signalling pathways and gene expression. The positive effects of polyphenols on glucose homeostasis observed in a large number of in vitro and animal models are supported by epidemiological evidence on polyphenol-rich diets. To confirm the implications of polyphenol consumption for prevention of insulin resistance, metabolic syndrome and eventually type 2 diabetes, human trials with well-defined diets, controlled study designs and clinically relevant end-points together with holistic approaches e.g., systems biology profiling technologies are needed.

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Impact of dietary polyphenols on carbohydrate metabolism.

The health benefits of green tea for a wide variety of ailments, including different types of cancer, heart disease, and liver disease, were reported. Many of these beneficial effects of green tea are related to its catechin, particularly (-)-epigallocatechin-3-gallate, content. There is evidence from in vitro and animal studies on the underlying mechanisms of green tea catechins and their biological actions. There are also human studies on using green tea catechins to treat metabolic syndrome, such as obesity, type II diabetes, and cardiovascular risk factors. Long-term consumption of tea catechins could be beneficial against high-fat diet-induced obesity and type II diabetes and could reduce the risk of coronary disease. Further research that conforms to international standards should be performed to monitor the pharmacological and clinical effects of green tea and to elucidate its mechanisms of action.

/pdf/beneficial-effects-of-green-tea-a-literature-review-3bxfzgkbiy.pdf

Beneficial effects of green tea: A literature review

Prevention of cancer through dietary intervention recently has received an increasing interest, and dietary polyphenols have become not only important potential chemopreventive, but also therapeutic, natural agents. Polyphenols have been reported to interfere at the initiation, promotion and progression of cancer. They might lead to the modulation of proteins in diverse pathways and require the integration of different signals for the final chemopreventive or therapeutic effect. Polyphenols have been demonstrated to act on multiple key elements in signal transduction pathways related to cellular proliferation, differentiation, apoptosis, inflammation, angiogenesis and metastasis; however, these molecular mechanisms of action are not completely characterized and many features remain to be elucidated. The aim of this review is to provide insights into the molecular basis of potential chemopreventive and therapeutic activities of dietary polyphenols with emphasis in their ability to control intracellular signalling cascades considered as relevant targets in a cancer preventive approach.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/mnfr.200700326

Cancer chemoprevention and chemotherapy: Dietary polyphenols and signalling pathways

As the prevalence of type 2 diabetes mellitus is increasing at an alarming rate, effective nutritional and exercise strategies for the prevention of this disease are required. Specific dietary components with antidiabetic efficacy could be one aspect of these strategies. This study investigated the antidiabetic effects of the most abundant green tea catechin, epigallocatechin gallate (EGCG, TEAVIGO), in rodent models of type 2 diabetes mellitus and H4IIE rat hepatoma cells. We assessed glucose and insulin tolerance in db/db mice and ZDF rats after they ingested EGCG. Using gene microarray and real-time quantitative RT-PCR we investigated the effect of EGCG on gene expression in H4IIE rat hepatoma cells as well as in liver and adipose tissue of db/db mice. EGCG improved oral glucose tolerance and blood glucose in food-deprived rats in a dose-dependent manner. Plasma concentrations of triacylglycerol were reduced and glucose-stimulated insulin secretion was enhanced. In H4IIE cells, EGCG downregulated genes involved in gluconeogenesis and the synthesis of fatty acids, triacylgycerol, and cholesterol. EGCG decreased the mRNA expression of phosphoenolpyruvate carboxykinase in H4IIE cells as well as in liver and adipose tissue of db/db mice. Glucokinase mRNA expression was upregulated in the liver of db/db mice in a dose-dependent manner. This study shows that EGCG beneficially modifies glucose and lipid metabolism in H4IIE cells and markedly enhances glucose tolerance in diabetic rodents. Dietary supplementation with EGCG could potentially contribute to nutritional strategies for the prevention and treatment of type 2 diabetes mellitus.

Epigallocatechin Gallate Supplementation Alleviates Diabetes in Rodents

A major component in green tea, epigallocatechin-3-gallate (EGCG), is reported to interfere with different steps of a number of inflammatory pathways. After oral administration, EGCG is retained in the gastrointestinal tract, where it is thought to exert preventive functions against inflammatory bowel disease and colon cancer. In this study, the human colon adenocarcinoma cell lines HT29 and T84 were used to investigate the effect of EGCG on intestinal inflammation. HT29 and T84 cells were stimulated with tumor necrosis factor (TNF)-alpha to induce the inflammatory condition and to trigger the inflammatory cascade in vitro and treated with EGCG to study its effect on inflammatory processes. The secretion of the chemokines interleukin (IL)-8, macrophage inflammatory protein (MIP)-3alpha, and prostaglandin E2 (PGE2) was determined by enzyme-linked immunosorbent assay. The gene expression level was measured by quantitative real-time polymerase chain reaction. Treatment of TNF-alpha-stimulated HT29 cells with EGCG dose-dependently inhibited the synthesis of IL-8, MIP-3alpha, and PGE2. Treatment with EGCG also inhibited the production of IL-8 and MIP-3alpha in TNF-alpha-stimulated T84 cells. Gene expression analysis in both HT29 and T84 cells revealed that EGCG down-regulates genes involved in inflammatory pathways. This study shows that EGCG acts broadly on the production of chemokines and PGE2 in the chemokine and eicosanoid pathways of colon epithelial cells. Therefore, EGCG might prove useful for the prevention and/or attenuation of colonic disorders.

Epigallocatechin-3-gallate impairs chemokine production in human colon epithelial cell lines.

The antioxidant activity of tocopherols in vegetable oils was shown to chiefly depend on the amount and the tocopherol homolog present. However, the most effective ratio of tocopherol homologs with regard to the antioxidant capacity has not been elucidated so far. The present study analyzed the effect of different tocopherol concentrations, homologs and ratios of homologs on markers of lipid oxidation in the most commonly consumed vegetable oils (canola, sunflower, soybean oil) stored in a 12 h light/dark cycle at 22 ± 2 °C for 56 days under retail/household conditions. After 56 days of storage, the α-tocopherol-rich canola and sunflower oil showed the strongest rise in lipid peroxides, yielding 25.1 ± 0.03 meq O2/kg (+25.3-fold) and 24.7 ± 0.05 meq O2/kg (+25.0-fold), respectively. ESR experiments, excluding effects of the oils’ matrices and other minor constituents, confirmed that a food representative tocopherol ratio of (γ + δ)/α = 4.77, as represented in soybean oil, led to a more pronounced delay of lipid oxidation than a lower ratio in canola (1.39) and sunflower oil (0.06). An optimum (γ + δ)/α -tocopherol ratio contributing to the oxidative quality of vegetable oils extending their shelf life has to be investigated.

https://www.mdpi.com/1420-3049/23/1/206/pdf/1

Contribution of the Ratio of Tocopherol Homologs to the Oxidative Stability of Commercial Vegetable Oils

Genistein, an isoflavone and phytoestrogen predominantly found in soy, is considered a potentially safe therapeutic option to prevent postmenopausal bone loss. A novel purified product consisting of 99.4% synthetic genistein aglycone was investigated in a phase 1 clinical study to assess safety and tolerability in healthy volunteers as well as to obtain pharmacokinetic data. Single oral doses of 30, 60, 150, or 300 mg were administered to 40 healthy volunteers in this prospective, randomized, open-label and sequential-group study. Tolerability of the different genistein doses was very good. No clinically significant effects on vital signs, ECG, and clinical laboratory parameters were observed. Genistein was rapidly absorbed and the kinetic profiles revealed a one-peak plasma concentration-time course. Mean Cmax values of 252.0, 605.0, 1518.0, and 1808.0 ng/mL were observed after 4.0 to 6.0 hours. The mean terminal elimination half-lives were calculated to be7.7, 7.5, 8.1, and 10.2 hours resulting in mean AUCs0-∞ of 2761.8, 8022.3, 21655.0, and 27537.8 ngxhr/mL. Linear regression of the dosenormalized AUCs0-∞ was not significantly different from zero, whereas the analysis for Cmax showed significance. Based on consecutive administration of single oral doses of genistein, dose linearity was assumed for extent of absorption [AUC0-∞] for all doses (30–300 mg) and for rate of absorption (Cmax) up to 150 mg. At the highest dose the intestinal rate of absorption of genistein seemed to be limited. Genistein was safe and well tolerated in the dose range investigated and showed nearly dose-linear pharmacokinetic characteristics.

Safety, tolerability, and pharmacokinetics of single ascending doses of synthetic genistein (Bonistein) in healthy volunteers.

A composition, useful in the prevention of osteoporosis, wherein said composition comprises (a) least one isoflavone and/or isoflavone glycoside, preferably genistein and/or genistin; (b) at least one polyunsaturated fatty acid; (c) optionally vitamin D, and /or one or more derivatives thereof and /or vitamin K and/or one or more derivatives thereof; and (d) optionally adjuvants and excipients in quantities as required, preferably within the range of 0.1 to 20 % by weight, based on the total weight of the composition. Dietary compositions and galenical forms made therefrom and the use of said compositions for preventing osteoporosis and stimulating osteogenesis in mammals.

Christoph Riegger

Papers

Epigallocatechin Gallate Supplementation Alleviates Diabetes in Rodents

Epigallocatechin-3-gallate impairs chemokine production in human colon epithelial cell lines.

Contribution of the Ratio of Tocopherol Homologs to the Oxidative Stability of Commercial Vegetable Oils

Safety, tolerability, and pharmacokinetics of single ascending doses of synthetic genistein (Bonistein) in healthy volunteers.

Composition for the prevention of osteoporosis comprising a combination of isoflavones and polyunsaturated fatty acids