The dietary consumption of grape and its products is associated with a lower incidence of degenerative diseases such as cardiovascular disease and certain types of cancers. Most recent interest has focused on the bioactive phenolic compounds in grape. Anthocyanins, flavanols, flavonols and resveratrol are the most important grape polyphenols because they possess many biological activities, such as antioxidant, cardioprotective, anticancer, anti-inflammation, antiaging and antimicrobial properties. This review summarizes current knowledge on the bioactivities of grape phenolics. The extraction, isolation and identification methods of polyphenols from grape as well as their bioavailability and potential toxicity also are included.
Anthocyanins (AC) are a group of water-soluble natural pigments found in various parts of higher plants. A very solid body of evidence indicates that these pigments possess properties potentially beneficial for human health thanks to different biological activities, and are able to protect against several human pathological conditions, including cardiovascular diseases. Many studies have highlighted that some health benefits of AC localize at the level of vessel endothelium, which contributes in multiple ways to vascular homeostasis, and also has an important functional role in the control of angiogenesis, inflammation, platelet aggregation, and vascular remodeling. Herein, we review the large existing literature concerning some of the molecular mechanisms that, beyond the antioxidant properties, may have a role in the effects of AC and AC-rich foods on vessel endothelium. For example, AC appears able to prevent peroxynitrite-mediated endothelial dysfunction in endothelial cells, not only due to their antioxidant activity, but also to their capability to regulate enzymes involved in NO activity. Furthermore, several evidences indicate that AC can prevent the expression of adhesion molecules and the adhesion of monocytes to ECs challenged by pro-inflammatory agents. Finally, the activity of AC on angiogenesis seems to involve their capability to modulate VEGF pathways. Dietary AC, despite their limited oral bioavailability and very low post-absorption plasma concentrations, may provide protection against oxidative stress-induced damage on vessel endothelium. However, the relationship between effective bioavailability and intracellular concentration of AC and their capability to protect vessel endothelium functions needs to be more deeply assessed.
Bergamot (Citrus bergamia Risso et Poiteau) fruits are characterized by a particularly high content and a unique composition of flavonoids, such as neoeriocitrin, neohesperidin, naringin, melitidin and brutieridin. Bergamot juice and its concentrate, highly enriched in polyphenols—here referred to as Bergamot Polyphenol Fraction (BPF)—has been evaluated in experimental and clinical studies. Studies performed in Italy and Australia showed that BPF treatment leads to an important reduction in lipid parameters in the blood of patients with hyperlipidemia ranging from 15 up to 40% for total cholesterol and cholesterol-LDL. A striking reduction (mean 41.0±2.6%) was also observed for plasma triglyceride levels, accompanied by a significant decrease in blood glucose (22.3±1.0%) in a subgroup of patients with metabolic syndrome. Although BPF cannot be proposed as a substitute for statins in patients at high risk of cardiovascular events, it offers an excellent alternative for low-risk and for statin-intolerant patients. The robust performance of BPF in clinical practice against cardiometabolic risk factors can be explained in the light of scientific evidence showing that bergamot flavonoids influence lipid and sugar metabolism acting as 3-hydroxy-3-methlglutaryl coenzyme A (HMG-CoA) reductase inhibitors and AMP kinase (AMPK) activators.
Iron deficiency is a serious health problem affecting people all over the globe, but mainly populations subsising on plant-based diets that are rich in compounds negatively influencing iron absorption. Polyphenols belong, together with phytic acid, to the major inhibitors of iron absorption. High concentrations of polyphenols can be found in numerous vegetables, legumes, fruits and beverages. The negative impact on iron bioavailability from these foods has largely been demonstrated in humans by iron isotope absorption studies; however, their impact on human iron status is still unclear. It is commonly assumed that, depending on their structure, polyphenols form insoluble complexes with iron in the gut and thereby inhibit its absorption. Recently, conducted Caco-2 cell studies suggest that polyphenols might increase apical iron uptake and that the inhibition is due to a decrease in basolateral exit. However, the complex formation of polyphenols and iron depends not only on polyphenol structure, but also on pH and the concentration of polyphenols and iron in the solution. Vitamin C and also EDTA, although the latter to a lesser extent, have been shown to protect iron against complex formation with polyphenols and increase its absorption. Adding these compounds to food, decreasing polyphenol activity, or reducing polyphenol concentration, are possible approaches to counteract the negative impact of polyphenols on iron bioavailability.
Cancer remains a major health problem and is one of the leading causes of deaths worldwide. It is a complex disease which can originate from several causes, and genome-wide association studies have indicated already the existence of several genetic variants that might contribute to the initiation or the progression of the disease. More recently, chronic inflammatory responses and epigenetic modulations came into the picture, and are being envisioned as key players in the development of most human cancers. Nowadays, it is generally accepted that lifestyle, including nutrition, can tremendously influence the overall health conditions. Numerous clinical and epidemiological studies could underline the beneficial role of several nutritional compounds including polyphenols. The most studied and promising examples of these dietary polyphenols include epigallocatechin-3-gallate (EGCG) from green tea, genistein from soybean, resveratrol from grapes and curcumin from turmeric. In a given compound, dose- and cell type-dependent manner, anti-inflammatory as well as epigenetics-regulatory functions could be attributed to these polyphenolic compounds, allowing for a potential therapeutic value. In this review we discuss the potential chemopreventive effect exerted by nutritional intake of phytotherapeutic compounds, more specifically dietary polyphenols, in cancer development via their effects on inflammatory and epigenetic pathways.
Ulcerative colitis (UC) is an idiopathic disease of the intestine. The etiology ranges from immune dysfunction, bacterial infiltration, and genetics to environment. Several medications have been employed to treat UC, but most have several side effects. To counter this problem, alternate therapy has been employed, which includes the use of plant-derived phytochemicals that have been investigated. Reports indicate them to be effective in reducing the severity of symptoms associated with UC with concomitant reductions in several markers of inflammation. This chapter deals with polyphenols in the prevention of UC due to their widely accepted benefits and ease of availability. Polyphenols have several applications, ranging from industrial to household and recently in medicine. They have been implicated in the treatment of several diseases and disorders like hypertension, allergies, cancer, diabetes, inflammatory bowel disease, hypercholesterolemia, and several other metabolic and genetic disorders. Several polyphenols, including curcumin and their role in the different pathways leading to the inflammation and pathology of UC, are discussed in this chapter. Curcumin is an active compound found in the turmeric plant and has been found to reduce inflammation, ulcerations and prevent the formation of the pre-cancerous lesions. Clinical trials have shown that curcumin could prevent clinical relapse in patients with inflammatory bowel disease (IBD) with an additional benefit of free radical scavenging leading to reduced oxidative stress. Tea, native to China and Southeast Asia, has several active components like catechins, flavonols, gallic acids and theanine, which were found to be protective against colitis by downregulation of pro-inflammatory cytokines and COX-2. Grape seed polyphenols were also found to be effective in reducing the macroscopic and microscopic lesions of colitis, histological score and reducing translocation of NF-κB in the colon mucosa. Cocoa, another common beverage and the content of chocolate, was found to be protective when co-administered with dextran sodium sulfate (DSS) and decreased colon crypt damage and leucocyte infiltration. Resveratrol is another common polyphenol produced by plants under stress led by pathogenic attack like bacteria and fungi. It is widely accepted for its anti-inflammatory and anti-cancerous effects and has also been found to reduce the pathology of UC. It mediates its protective effects by decreasing neutrophil's percentage and downregulation of inflammatory markers with reduced myeloperoxidase (MPO) and lipid peroxidation in colon. It is mainly found in the skin of red grapes. Therefore, although the amount in red wine is insignificant, it is available commercially for use as a supplement. Quercetin, silymarin, kaempferol, ellagic acid, and rutoside are some of the other polyphenols discussed in this chapter. They were found to be effective in reducing the pathology and symptoms associated with UC. There are very few studies that indicate the adverse effects of these polyphenols, including the oral administration of 1% green tea polyphenols which increased kidney weight and decreased mRNA expression of HSPs and several antioxidant enzymes. There could be a few exceptions regarding the safety of the use of polyphenols as therapeutic agents in the treatment of UC, and hence more intensive research is needed to declare polyphenols, or any other phytochemicals obtained, as safe for medicinal use. Also, their dosage and the adverse effects of different polyphenols in different disease models need to be established with human studies before the declaration of their use in a particular disease.
Polyphenols are among the most abundant and beneficial antioxidants in nature. This review examines the virtues of various polyphenols and recommends quercetin dihydrate flavonoid and soluble orthoproanthocyanidin (OPC) flavanol, with or without ellagic acid, as the dream team that supports safer, and more effective, protection from free radical damage. The discussion includes tests of antioxidant potency such as ORAC and surveys the research evidence on functional benefits of these nutrients. Key predictive biomarkers are reviewed that can be used as valuable tools in clinical assessment of risk and resilience. Biochemical individuality supports supplement use in physiologically meaningful amounts for each individual, monitored through predictive biomarker lab tests to determine individual need. Predictive biomarker tests are more helpful when interpreted or referenced to best outcome goal values.
Green tea is credited to be the second most consumed beverage in the world after water and is one of the most ancient and popular therapeutic beverages. Green tea contains high concentrations of catechins and its regular consumption has long been associated with myriad health benefits against a wide array of diseases that include diabetes, inflammation, clastogenesis, vomiting, diarrhea, cardiac ailments and several types of cancer. More recently, a large number of scientific studies with experimental animals have shown that tea reduces liver injury caused by alcohol, carbon tetrachloride, ischemic-reperfusion, lead, viral hepatitis, phenobarbitol, microcystin, azathioprine, galactosamine and lipopolysaccharide. Additionally, studies have also shown that tea prevents chemical-induced hepatocarcinogenesis. This review summarizes the results related to the hepatoprotective properties of tea and emphasizes the aspects that warrant future research to establish its activity and utility in humans.
The Kingdom of Saudi Arabia is situated largely in a desert biome. The native flora contributes many plants utilized in traditional medicine systems. These herbal remedies are often used as complements or alternatives to allopathic medicine. Unfortunately, in keeping with worldwide trends, the incidence and prevalence of chronic diseases such as type 2 diabetes mellitus, and cancers in Saudi Arabia has been increasing. Thus, herbal remedies continue to be utilized for their purported role in prevention and treatment of diseases. Also, there is growing scientific inquiry regarding the secondary metabolite (natural product) profiles and activities of plants that show therapeutic promise. Two members of the Capparidaceae plant family (Capparis spinosa L. and Capparis decidua (Forssk.) Edgew.) are discussed in regard to secondary metabolites and activities relevant to diabetes. The Asclepiadaceae family members Calotropis procera (Aiton) Dryand. and Caralluma tuberculata N.E.Br. are discussed in regard to relevant natural products and activities with relevance to cancer.
Epidemiological studies have shown that the consumption of green tea is associated with the prevention of many types of cancer, including breast, lung, colon and prostate cancers. Polyphenols are major bioactive constituents of green tea that possess anticancer activities. The molecular basis of the anticancer effects of green tea polyphenols is still under investigation. Research is largely focused on particular types of cancers and their underlying mechanisms. Green tea polyphenols appear to prevent many types of cancers through numerous mechanisms, including redox reactivity, protein binding, and synergism with commonly used cancer therapies. The variable results of chemoprevention by green tea polyphenols may be due, in part, to differences in metabolism of these bioactive components. Studies in this area are largely focused on understanding and modulating the bioavailability of green tea polyphenols. Until the bioavailability and toxicological issues of these compounds are better understood, a moderate view regarding their consumption is suggested.
As flavonoids and stilbenes are typical examples of polyphenolic compounds in nature, their potentials for human health benefits have been widely known as anti-inflammatory, anticancer, and antiviral agents, as well as antioxidants. In addition to drug development, their application as coloring agents, cosmetic materials, and dietary supplements have resulted in great interest in the mass production of flavonoids and stilbenes through various methodologies. Production in recombinant microorganisms provides an attractive alternative to plant extraction and chemical synthesis due to increased cost and time efficiency. Microbes can be engineered to produce complex structures from simple, inexpensive precursors under standardized control. As metabolic engineering methods and strategies continue to develop and diversify, production yields of target molecules continue to improve. This chapter describes the importance of the pharmacological properties of flavonoids and stilbenes and discusses strategies for their biosynthesis in microorganisms using metabolic engineering techniques.
Green tea (Camellia sinensis) is a widely consumed beverage that has shown preventive effects against chronic diseases including cancer. Green tea polyphenols are believed to be responsible for this cancer preventive effect and modulation of redox activity has been suggested as a potential mechanism of action. Data from various laboratories have suggested that green tea polyphenols can act as direct antioxidants by scavenging reactive oxygen species or chelating transition metals; as potent pro-oxidants which generate reactive oxygen species via a transition metal catalyzed reaction; or indirectly to modulate redox status by upregulating of phase II and antioxidant enzymes. Considerable data has been generated using in vitro systems, but these results must be interpreted with caution because of the relatively high oxygen concentrations available in vitro compared to in vivo. In the present review, we discuss the available data regarding the pro-oxidant and antioxidant effects of tea polyphenols and provide suggestions for future research.
Since oxidative stress is a causal factor in many chronic and degenerative pathologies, considerable effort has been made to find antioxidant compounds that prevent the onset of these diseases and counteract their progression. In fact, numerous polyphenols possess radical scavenging/antioxidant activity, especially when studied in cell-free systems as well as in cells in vitro, or even in vivo. Polyphenols—natural compounds with variable phenolic structures—are common in vegetables, fruit, grain, bark, roots, tea and wine. All polyphenols contain one or more aromatic rings with more than one hydroxyl group. They are generally classified into four different groups, depending on the number of phenol rings and chemical groups bound to the rings: flavonoids, phenolic acids, stilbenes, and lignans. This chapter reviews recent work on the capacity of polyphenols to protect cells against oxidative insult.
Flaxseed, a small brown seed produced from the blue flowers of the flax crop Linum usitatissimum, is the richest plant source of omega-3-poly unsaturated fatty acid (n-3 PUFA); i.e., α-linolenic acid (ALA) and lignan secoisolariciresinol diglucoside (SDG). In 1956, Bakke and Klosterman (Bakke JE, Klosterman HJ. A new diglucoside from flaxseed. Proc Natl Acad Sci USA 1956;10:18–21) originally isolated SDG from flaxseed. Other phenolics in flaxseed are, for example, coumaric, caffeic, ferulic and sinapic acids. Flaxseed has gained much importance in recent times as an ethnomedicine due to its wide pharmacological actions mainly due to lipid-lowering action, which is attributed to SDG lignan. Flax lignan has been reported for its preventative action in various cardiovascular complications such as atherosclerosis, hyperlipidemia, ischemia, hypertension and cardiotoxicity by preclinical and clinical studies. There have not, so far, been sufficient studies on the toxicity profile of flaxseed. However, caution is suggested for consuming flaxseed by pregnant women.
Hypertension is a major public health problem, and a leading cause of premature death and disability in both developed and developing countries, affecting one-quarter of the world’s adult population. It is also one of the main cardiovascular risk factors in the elderly. The first steps for the management of hypertension involve following a healthy diet, and modifying lifestyle, including smoking cessation, moderate alcohol consumption, sodium intake restriction, weight reduction, and regular physical activity. Several observational and intervention studies have found an inverse association between the risk of cardiovascular disease and the consumption of polyphenol-rich foods and beverages such as cocoa, fruit and vegetables, tea, virgin olive oil, and wine. This paper reviews the recent clinical and epidemiological studies on the relationship between polyphenol intake and blood pressure, as well as the plausible mechanisms of action for a cardioprotective role of polyphenols. We describe how the vasoprotective effect of dietary polyphenols has been related to their ability to increase endothelial synthesis of nitric oxide and endothelium-derived hyperpolarizing factor-mediated responses.
The general term polyphenols encompasses many chemicals with the same general structure. Polyphenols are complex antioxidants with increasing public health significance, particularly in the areas of nutrition, epidemiology, and primary, secondary, and tertiary prevention. Consumption of foods containing polyphenolic compounds is common, as the chemical is in many recommended foods. Dietary supplements containing polyphenols are also currently marketed in the United States, though there are at present no governmental dietary recommendations for polyphenols. Increasing epidemiologic research will further the application of polyphenols in public health by providing evidence for dietary recommendations as well as the promotion of consumption to prevent current challenging diseases such as diabetes and various cancers.
Epidemiological evidence supports the claim that diets rich in polyphenols lead to a relative improvement in aging. In fact, it has been reported that healthy centenarians show low levels of inflammatory biomarkers, and polyphenols as anti-inflammatory agents may prevent chronic diseases and extend human life. The objective of the current chapter is to summarize the key findings and progresses made in polyphenols, which exert as anti-inflammatory ingredients in numerous chronic diseases, such as cardiovascular diseases, metabolic diseases, cancer, and neurodegenerative disorders. Special emphasis is placed on highlighting the key effects of polyphenols on the cellular redox system, arachidonic acid metabolisim (phospholipase A, cyclooxygenase, and lipoxygenase), nitric oxide synthase, proinflammatory molecules (cytokines, chemokines, adhesion molecules, and C-reactive protein), and inflammatory gene expression (transcription factors NF-κB, AP-1, STAT-1, and C/EBP; nuclear molecules PPAR, PARP, CBP, p300 (HAT) and HDACs; and protein kinases).
