Dietary flavonoid aglycones and their glycosides: Which show better biological significance?
15 Jul 2015-Critical Reviews in Food Science and Nutrition (Crit Rev Food Sci Nutr)-Vol. 57, Iss: 9, pp 1874-1905
TL;DR: With in vivo (oral) treatment, flavonoids glycosides showed similar or even higher antidiabetes, anti-inflammatory, antidegranulating, antistress, and antiallergic activity than their flavonoid aglycones.
Abstract: The dietary flavonoids, especially their glycosides, are the most vital phytochemicals in diets and are of great general interest due to their diverse bioactivity. The natural flavonoids almost all exist as their O-glycoside or C-glycoside forms in plants. In this review, we summarized the existing knowledge on the different biological benefits and pharmacokinetic behaviors between flavonoid aglycones and their glycosides. Due to various conclusions from different flavonoid types and health/disease conditions, it is very difficult to draw general or universally applicable comments regarding the impact of glycosylation on the biological benefits of flavonoids. It seems as though O-glycosylation generally reduces the bioactivity of these compounds - this has been observed for diverse properties including antioxidant activity, antidiabetes activity, anti-inflammation activity, antibacterial, antifungal activity, antitumor activity, anticoagulant activity, antiplatelet activity, antidegranulating activity, antitrypanosomal activity, influenza virus neuraminidase inhibition, aldehyde oxidase inhibition, immunomodulatory, and antitubercular activity. However, O-glycosylation can enhance certain types of biological benefits including anti-HIV activity, tyrosinase inhibition, antirotavirus activity, antistress activity, antiobesity activity, anticholinesterase potential, antiadipogenic activity, and antiallergic activity. However, there is a lack of data for most flavonoids, and their structures vary widely. There is also a profound lack of data on the impact of C-glycosylation on flavonoid biological benefits, although it has been demonstrated that in at least some cases C-glycosylation has positive effects on properties that may be useful in human healthcare such as antioxidant and antidiabetes activity. Furthermore, there is a lack of in vivo data that would make it possible to make broad generalizations concerning the influence of glycosylation on the benefits of flavonoids for human health. It is possible that the effects of glycosylation on flavonoid bioactivity in vitro may differ from that seen in vivo. With in vivo (oral) treatment, flavonoid glycosides showed similar or even higher antidiabetes, anti-inflammatory, antidegranulating, antistress, and antiallergic activity than their flavonoid aglycones. Flavonoid glycosides keep higher plasma levels and have a longer mean residence time than those of aglycones. We should pay more attention to in vivo benefits of flavonoid glycosides, especially C-glycosides.
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TL;DR: This review focuses on the biotransformation of polyphenols by gut microbiota, modulation of gut microbiota bypolyphenols, and the effects of these two-way mutual interactions on polyphenol bioavailability, and ultimately, human health.
Abstract: As of late, polyphenols have increasingly interested the scientific community due to their proposed health benefits. Much of this attention has focused on their bioavailability. Polyphenol–gut microbiota interactions should be considered to understand their biological functions. The dichotomy between the biotransformation of polyphenols into their metabolites by gut microbiota and the modulation of gut microbiota composition by polyphenols contributes to positive health outcomes. Although there are many studies on the in vivo bioavailability of polyphenols, the mutual relationship between polyphenols and gut microbiota is not fully understood. This review focuses on the biotransformation of polyphenols by gut microbiota, modulation of gut microbiota by polyphenols, and the effects of these two-way mutual interactions on polyphenol bioavailability, and ultimately, human health.
527 citations
TL;DR: It is possible that a lower dosage from plant sources could be effective due to of its higher bioavailability compared to the aglycone form, and studies are needed to evaluate the potential cardiovascular benefits of plants rich in quercetin and kaempferol glycoside conjugates.
Abstract: Fruit and vegetable intake has been associated with a reduced risk of cardiovascular disease. Quercetin and kaempferol are among the most ubiquitous polyphenols in fruit and vegetables. Most of the quercetin and kaempferol in plants is attached to sugar moieties rather than in the free form. The types and attachments of sugars impact bioavailability, and thus bioactivity. This article aims to review the current literature on the bioavailability of quercetin and kaempferol from food sources and evaluate the potential cardiovascular effects in humans. Foods with the highest concentrations of quercetin and kaempferol in plants are not necessarily the most bioavailable sources. Glucoside conjugates which are found in onions appear to have the highest bioavailability in humans. The absorbed quercetin and kaempferol are rapidly metabolized in the liver and circulate as methyl, glucuronide, and sulfate metabolites. These metabolites can be measured in the blood and urine to assess bioactivity in human trials. The optimal effective dose of quercetin reported to have beneficial effect of lowering blood pressure and inflammation is 500 mg of the aglycone form. Few clinical studies have examined the potential cardiovascular effects of high intakes of quercetin- and kaempferol-rich plants. However, it is possible that a lower dosage from plant sources could be effective due to of its higher bioavailability compared to the aglycone form. Studies are needed to evaluate the potential cardiovascular benefits of plants rich in quercetin and kaempferol glycoside conjugates.
347 citations
Cites background from "Dietary flavonoid aglycones and the..."
...Flavonols in plants, however, are synthesized linked to sugar conjugates, and thus have different bioavailability than the free forms [9]....
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TL;DR: The aim of this paper was to summarize the recent investigations and findings regarding in vitro and animal model studies on the anti-inflammatory effects of fruits, vegetables, and food legumes and phytochemicals are discussed as the natural promotion strategy for the improvement of human health status.
Abstract: Inflammation is the first biological response of the immune system to infection, injury or irritation. Evidence suggests that the anti-inflammatory effect is mediated through the regulation of various inflammatory cytokines, such as nitric oxide, interleukins, tumor necrosis factor alpha-α, interferon gamma-γ as well as noncytokine mediator, prostaglandin E2. Fruits, vegetables, and food legumes contain high levels of phytochemicals that show anti-inflammatory effect, but their mechanisms of actions have not been completely identified. The aim of this paper was to summarize the recent investigations and findings regarding in vitro and animal model studies on the anti-inflammatory effects of fruits, vegetables, and food legumes. Specific cytokines released for specific type of physiological event might shed some light on the specific use of each source of phytochemicals that can benefit to counter the inflammatory response. As natural modulators of proinflammatory gene expressions, phytochemical from fruits, vegetables, and food legumes could be incorporated into novel bioactive anti-inflammatory formulations of various nutraceuticals and pharmaceuticals. Finally, these phytochemicals are discussed as the natural promotion strategy for the improvement of human health status. The phenolics and triterpenoids in fruits and vegetables showed higher anti-inflammatory activity than other compounds. In food legumes, lectins and peptides had anti-inflammatory activity in most cases. However, there are lack of human study data on the anti-inflammatory activity of phytochemicals from fruits, vegetables, and food legumes.
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TL;DR: A comprehensive review of recent progress in the research of plant flavonoids, focusing on their biosynthesis (pathway and transcription factors) and bioactive mechanisms based on epidemic evidence, in vitro and in vivo research, and bioavailability in the human body is presented in this paper .
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TL;DR: Conclusive clinical trials of the phenolic compounds present in PoP are essential for correct validation of their health benefits and are mainly assessed by in vitro experimentation.
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References
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TL;DR: The factors underlying the influence of the different classes of polyphenols in enhancing their resistance to oxidation are discussed and support the contention that the partition coefficients of the flavonoids as well as their rates of reaction with the relevant radicals define the antioxidant activities in the lipophilic phase.
8,513 citations
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...It illustrated that the glycosylation of flavonol on both OCH3 and OH groups reduced the DPPH free radical scavenging potential (Rice-Evans et al., 1996; Cai et al., 2006; Om et al., 2008; De Martino et al., 2012; Sarkar et al., 2012; Wang et al., 2012b)....
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...…10, 1uercetin/1uercetin 3-O-glucoside-7- Orhamnoside, 11. hesperetin/hesperetin 7-O-rutinoside, 12. kaempferol/kaempferol 3-O-glucoside (Rice-Evans et al., 1996; Burda and Oleszek, 2001; Mishra et al., 2003; Majo et al., 2005; Cai et al., 2006; Om et al., 2008; Liu et al., 2009; Kim et…...
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TL;DR: This integrating paradigm provides a new conceptual framework for future research and drug discovery in diabetes-specific microvascular disease and seems to reflect a single hyperglycaemia-induced process of overproduction of superoxide by the mitochondrial electron-transport chain.
Abstract: Diabetes-specific microvascular disease is a leading cause of blindness, renal failure and nerve damage, and diabetes-accelerated atherosclerosis leads to increased risk of myocardial infarction, stroke and limb amputation. Four main molecular mechanisms have been implicated in glucose-mediated vascular damage. All seem to reflect a single hyperglycaemia-induced process of overproduction of superoxide by the mitochondrial electron-transport chain. This integrating paradigm provides a new conceptual framework for future research and drug discovery.
8,289 citations
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TL;DR: From seven structurally divergent groups of flavonoids, only flavonols with a free hydroxyl group at the C-3 position of the flavonoid skeleton showed high inhibitory activity to beta-carotene oxidation.
Abstract: The relationship between the structure of 42 flavonoids and their antioxidant and antiradical activities was elucidated by heat-induced oxidation in a beta-carotene and linoleic acid system and by the 1,1-diphenyl-2-picrylhydrazyl decoloration test. From seven structurally divergent groups of flavonoids, only flavonols with a free hydroxyl group at the C-3 position of the flavonoid skeleton showed high inhibitory activity to beta-carotene oxidation. Antiradical activity depended on the presence of a flavonol structure or free hydroxyl group at the C-4' position. The effect of the 4'-hydroxyl was strongly modified by other structural features, such as the presence of free hydroxyls at C-3 and/or C-3' and a C2-C3 double bond.
1,089 citations
"Dietary flavonoid aglycones and the..." refers background in this paper
...Burda and Oleszek (2001) compared the antioxidant activity of flavonoids characterized by the potential to inhibit heatinduced oxidation in a b-carotene-linoleic acid-model system....
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...…3-O-glucoside-7- Orhamnoside, 11. hesperetin/hesperetin 7-O-rutinoside, 12. kaempferol/kaempferol 3-O-glucoside (Rice-Evans et al., 1996; Burda and Oleszek, 2001; Mishra et al., 2003; Majo et al., 2005; Cai et al., 2006; Om et al., 2008; Liu et al., 2009; Kim et al., 2011a; Sarkar et…...
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...kaempferol/kaempferol 3-O-glucoside (Rice-Evans et al., 1996; Burda and Oleszek, 2001; Mishra et al., 2003; Majo et al., 2005; Cai et al., 2006; Om et al., 2008; Liu et al., 2009; Kim et al., 2011a; Sarkar et al., 2012 Wang et al., 2012; Okoth et al., 2013; Tronina et al., 2013)....
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TL;DR: The distribution of ka Kempferol in the plant kingdom and its pharmacological properties are reviewed and the pharmacokinetics and safety of kaempferol are analyzed to help understand the health benefits of kaEMPferol-containing plants and to develop this flavonoid as a possible agent for the prevention and treatment of some diseases.
Abstract: Epidemiological studies have revealed that a diet rich in plant-derived foods has a protective effect on human health. Identifying bioactive dietary constituents is an active area of scientific investigation that may lead to new drug discovery. Kaempferol (3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) is a flavonoid found in many edible plants (e.g. tea, broccoli, cabbage, kale, beans, endive, leek, tomato, strawberries and grapes) and in plants or botanical products commonly used in traditional medicine (e.g. Ginkgo biloba, Tilia spp, Equisetum spp, Moringa oleifera, Sophora japonica and propolis). Some epidemiological studies have found a positive association between the consumption of foods containing kaempferol and a reduced risk of developing several disorders such as cancer and cardiovascular diseases. Numerous preclinical studies have shown that kaempferol and some glycosides of kaempferol have a wide range of pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, anticancer, cardioprotective, neuroprotective, antidiabetic, anti-osteoporotic, estrogenic/antiestrogenic, anxiolytic, analgesic and antiallergic activities. In this article, the distribution of kaempferol in the plant kingdom and its pharmacological properties are reviewed. The pharmacokinetics (e.g. oral bioavailability, metabolism, plasma levels) and safety of kaempferol are also analyzed. This information may help understand the health benefits of kaempferol-containing plants and may contribute to develop this flavonoid as a possible agent for the prevention and treatment of some diseases.
987 citations
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TL;DR: Flavonoids are a family of plant-derived compounds with potentially exploitable activities, including direct antibacterial activity, synergism with antibiotics, and suppression of bacterial virulence, and recent advances towards understanding these properties are described.
985 citations
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