Modifications of dietary flavonoids towards improved bioactivity: An update on structure–activity relationship

Over the past two decades, extensive studies have revealed that inflammation represents a major risk factor for various human diseases. Chronic inflammatory responses predispose to pathological progression of chronic illnesses featured with penetration of inflammatory cells, dysregulation of cellular signaling, excessive generation of cytokines, and loss of barrier function. Hence, the suppression of inflammation has the potential to delay, prevent, and to treat chronic diseases. Flavonoids, which are widely distributed in humans daily diet, such as vegetables, fruits, tea and cocoa, among others, are considered as bioactive compounds with anti-inflammatory potential. Modification of flavonoids including hydroxylation, o-methylation, and glycosylation, can alter their metabolic features and affect mechanisms of inflammation. Structure–activity relationships among naturally occurred flavonoids hence provide us with a preliminary insight into their anti-inflammatory potential, not only attributing to the antioxidant capacity, but also to modulate inflammatory mediators. The present review summarizes current knowledge and underlies mechanisms of anti-inflammatory activities of dietary flavonoids and their influences involved in the development of various inflammatory-related chronic diseases. In addition, the established structure–activity relationships of phenolic compounds in this review may give an insight for the screening of new anti-inflammatory agents from dietary materials.     

Fruit Polyphenols: A Review of Anti-inflammatory Effects in Humans

Underlying etiological factors in the development of obesity-related chronic diseases are long-term imbalances of oxidative and inflammatory stress leading to tissue dysfunction, damage, and ultimately failure. Poor dietary quality contributes significantly to the oxidative and inflammatory status of an individual. Conversely, various dietary approaches, including specific dietary factors can mitigate or prevent the occurrence of these risk-conferring imbalances brought about by modern lifestyle. Plant-derived polyphenolic compounds are well known for their antioxidant properties. Recent evidence indicates these compounds may confer anti-inflammatory and/or inflammatory response stabilizing activities, which would have important implications in health maintenance and disease risk reduction. Commonly consumed fruits, such as grapes, berries, and oranges/orange juice, contain polyphenolic compounds that have been studied for their effects on inflammation, but the nature and extent of their effects in humans remain unclear. Therefore, this article aims to provide a comprehensive overview of human clinical trials investigating the acute and chronic (feeding) effect of polyphenols from commonly consumed fruits or their derived products on inflammation.     

The therapeutic potential of plant flavonoids on rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune condition that mainly affects peripheral joints. Although immunosuppressive drugs and non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat this condition, these drugs have severe side effects. Flavonoids are the most abundant phenolic compounds which exhibit anti-oxidant, anti-inflammatory and immunomodulatory properties. Many bioactive flavonoids have powerful anti-inflammatory effects. However, a very few have reached clinical use. Dietary flavonoids have been reported to control joint inflammation and alleviate arthritis symptoms in both human RA and animal models of arthritis. There is little scientific evidence about their mechanism of actions in RA. We review the therapeutic effects of different groups of flavonoids belonging to the most common and abundant groups on RA. In particular, the probable mechanisms of major flavonoids on cells and chemical messengers involved in the inflammatory signaling components of RA are discussed in detail.     

抗炎低聚糖的制备及其抗炎机制研究进展

炎症是机体对各种致炎因素及损伤的一种防御反应,也是许多慢性疾病发生的关键因素.研究表明低聚糖具有抗炎、抗菌、抗氧化和抗癌等多种生理活性.作为新型功能性糖源,低聚糖具有低热量、高溶解度、促进双歧杆菌增殖等特点.本文对近年来具有抗炎活性低聚糖的种类和制备方法进行介绍,并从炎症介质和炎症信号通路两方面对其抗炎机制进行综述,以...     

黄酮类化合物吸收代谢及其对胃肠道功能影响的研究进展

黄酮类化合物是一大类重要的植物次生代谢产物,既具有良好的药理活性,也是重要的营养因子。它的吸收、代谢及排泄等均在胃肠道内完成,在胃肠道中发挥多种生理功能,包括抗氧化、抗炎、抗癌、调节肠道菌群等。因此,近年来已有大量研究报道了有关黄酮类化合物在消化道中的消化、吸收规律,并针对黄酮类化合物的功能活性将其开发用于针对消化道疾病的各种新型食品、药品、保健品中。本文就近年来黄酮类化合物在胃肠道中代谢规律及其对人类健康效应相关研究进行了综述,旨在为黄酮类化合物在预防肠道疾病中的应用及作为新型功能性食品的开发提供参考。     

蛋源性活性组分对炎症性肠病的缓解作用研究进展

炎症性肠病是发生在肠道的慢性且反复发作的炎性疾病。传统的药物治疗虽能缓解临床症状但却存在一 定的副作用。蛋源性活性组分是近期食品科学领域研究的热点之一,禽蛋组分的抗菌、抗病毒、降血压、抗氧 化、抗炎以及免疫调节等功能活性已被相继证实。蛋源性活性组分的开发应用有望为炎症性肠病提供新的治疗策 略。本文综述了氨基酸、多肽、蛋白质和脂质这些蛋源性活性组分的抗炎活性以及其对炎症性肠病缓解作用的分 子作用机制的研究进展,并对其研究进行了展望,以期为蛋源性抗肠炎活性组分的进一步深入研究和应用开发提 供参考。     

花生四烯酸、二十二碳六烯酸和二十碳五烯酸 在炎症中的作用概述

心脑血管疾病、肿瘤、糖尿病、神经系统疾病、自身免疫等疾病严重危害着人类的生命和健康,并消耗着大量医疗资源。事实上,很多疾病发生和发展的背后都伴随着炎症反应,炎症是众多疾病的病理基础,甚至是导致这些疾病的诱因。炎症本身是机体的防御性反应,但过度的炎症反应和长期慢性炎症会损害机体的稳态。炎症的调节和控制由炎症介质介导,花生四烯酸(arachidonic acid,AA)、二十二碳六烯酸(docosahexaenoic acid,DHA)和二十碳五烯酸(eicosapentaenoic acid,EPA)等长链多不饱和脂肪酸(10ng-chain polyunsaturated fatty acids,LC-PUFAs)的衍生物是一类重要的调控炎症的介质。炎性细胞间的交流和细胞内信号传递与LC-PUFAs有关。AA经环氧酶和脂氧合酶合成的类二十烷酸主要起促炎作用,但有的也有抗炎作用。DHA和EPA在体内起抗炎作用,由它们合成的消退素(resolvins,Rvs)和保护素(protectin,PD)是重要的抗炎活性物质。DHA和EPA还可以干扰炎性细胞内信号传导途径来抑制炎症反应。本文从炎症与疾病的关系、LC-PUFAs的衍生物及其促炎和抗炎机制等方面综述了AA、DHA和EPA在炎症中的作用。     

Regulatory Roles of Flavonoids on Inflammasome Activation during Inflammatory Responses

Inflammation is an innate immune response to noxious stimuli to protect the body from pathogens. Inflammatory responses consist of two main steps: priming and triggering. In priming, inflammatory cells increase expressions of inflammatory molecules, while in triggering, inflammasomes are activated, resulting in cell death and pro‐inflammatory cytokine secretion. Inflammasomes are protein complexes comprising intracellular pattern recognition receptors (PRRs) (e.g., nucleotide‐binding oligomerization domain‐like receptors (NLRs), absent in melanoma 2 (AIM2), and caspases‐4/5/11) and pro‐caspase‐1 with or without a bipartite adaptor molecule ASC. Inflammasome activation induces pyroptosis, inflammatory cell death, and stimulates caspase‐1‐mediated secretion of interleukin (IL)‐1b and IL‐18. Flavonoids are secondary metabolites found in various plants and are considered as critical ingredients promoting health and ameliorating various disease symptoms. Anti‐inflammatory activity of flavonoids and underlying mechanisms have been widely studied. This review introduces current knowledge on different types of inflammasomes and their activation during inflammatory responses and discusses recent studies regarding anti‐inflammatory roles of flavonoids as suppressors of inflammasomes in inflammatory conditions. Understanding the regulatory effects of flavonoids on inflammasome activation will increase our knowledge of flavonoid‐mediated anti‐inflammatory activity and provide new insights into the development of flavonoid preparations to prevent and treat human inflammatory diseases.     

A comprehensive review of the metabolism of citrus flavonoids and their binding to bitter taste receptors

Citrus is an important source of flavonoids in our daily diet. Citrus flavonoids have antioxidant, anticancer, anti-inflammatory, and cardiovascular disease prevention functions. Studies have shown that some pharmaceutical values of flavonoids may be related to their binding to bitter taste receptors, thus activating downstream signal transduction pathways; however, the underlying mechanism has not been systematically elucidated. In this paper, the biosynthesis pathway and the absorption and metabolism of citrus flavonoids were briefly reviewed, and the relationship between flavonoid structure and bitter taste intensity was investigated. In addition, the pharmacological effects of bitter flavonoids and the activation of bitter taste receptors in combating various diseases were discussed. This review provides an important basis for the targeted design of citrus flavonoid structures to make them more biologically active and more attractive as powerful drugs for the effective treatment of chronic diseases such as obesity, asthma, and neurological diseases.     

黄酮类化合物与其他化合物相互作用的研究进展

黄酮类化合物是一类广泛存在于植物根、茎、叶、花和果实中的次生代谢有机物,其结构复杂,种类繁 多,因其对人类健康有很强的积极作用,如抗癌、抗菌、抗病毒、抗炎症、抗过敏等而备受关注,人们通过体内、 体外实验验证了其多种生物活性。然而黄酮类化合物通常与其他种类化合物如碳水化合物、蛋白质、脂质、酸等在植 物体内共存,与它们一起摄入人体内并且可以与其他化合物相互影响或者结合,因此黄酮类化合物的功能与其他化合 物有着密不可分的联系。本文综述了黄酮类化合物与其他化合物之间的相互作用,并阐述了其作用机制与结果。     

Protective roles of flavonoids and flavonoid-rich plant extracts against urolithiasis: A review

In the urinary system, urolithiasis is the third prevalent disorder which causes severe pain in individuals. Urinary stones are composed of calcium oxalate (CaOx) and calcium phosphate in approximately 80% of patients. Although various drugs and surgery operations are used to treat the disease, side effects of drugs and the high recurrence after therapy in patients cannot be ignored. Flavonoids are a large group of plant polyphenols with presumed beneficial effects on several common diseases. Whereas, a very few have reached clinical use. The results of recent studies have shown that the plant flavonoids could effectively inhibit the formation of CaOx stones in vitro and in vivo, correlating with their diuretic, antioxidant, anti-inflammatory, antibacterial properties and other protective effects. Thus, the flavonoids or flavonoid-rich plant extracts endowed with anti-urolithiasis activities and probable mechanisms of actions were reviewed. In addition, we also put forward some issues needed to be concerned in future investigations as well as offered prospects and challenges for developing the plant flavonoids into drugs for stone prevention.     

肠道菌群促炎与动脉粥样硬化关系研究进展

人类肠道菌群由近百万亿个共生微生物组成,以人体内的营养成分维持生存和代谢,通过代谢和免疫功能来维持人类身体健康.肠道菌群与全身的疾病密切相关.肠道菌群组成、特异性菌种或菌群的变化与各类疾病如糖尿病、肥胖、炎症及心血管疾病的发生有密切的相关性.心血管疾病的发病率和死亡率在全球呈上升的趋势,严重危害人类健康.动脉粥样硬化(...     

Inflammatory Diseases and Vitamin E—What Do We Know and Where Do We Go?

Inflammation‐driven diseases and related comorbidities, such as the metabolic syndrome, obesity, fatty liver disease, and cardiovascular diseases cause significant global burden. There is a growing body of evidence that nutrients alter inflammatory responses and can therefore make a decisive contribution to the treatment of these diseases. Recently, the inflammasome, a cytosolic multiprotein complex, has been identified as a key player in inflammation and the development of various inflammation‐mediated disorders, with nucleotide‐binding domain and leucine‐rich repeat pyrin domain (NLRP) 3 being the inflammasome of interest. Here an overview about the cellular signaling pathways underlying nuclear factor “kappa‐light‐chain‐enhancer” of activated B‐cells (NF‐κB)‐ and NLRP3‐mediated inflammatory processes, and the pathogenesis of the inflammatory diseases atherosclerosis and non‐alcoholic fatty liver disease (NAFLD) is provided; next, the current state of knowledge for drug‐based and dietary‐based interventions for treating cardiovascular diseases and NAFLD is discussed. To date, one of the most important antioxidants in the human diet is vitamin E. Various in vitro and in vivo studies suggest that the different forms of vitamin E and also their derivatives have anti‐inflammatory activity. Recent publications suggest that vitamin E—and possibly metabolites of vitamin E—are a promising therapeutic approach for treating inflammatory diseases such as NAFLD.     

Effects of flavonoids and other polyphenols on inflammation

Flavonoids are a family of polyphenolic compounds which are widespread in nature (vegetables) and are consumed as part of the human diet in significant amounts. There are other types of polyphenols, including, for example, tannins and resveratrol. Flavonoids and related polyphenolic compounds have significant antiinflammatory activity, among others. This short review summarizes the current knowledge on the effects of flavonoids and related polyphenolic compounds on inflammation, with a focus on structural requirements, the mechanisms involved, and pharmacokinetic considerations. Different molecular (cyclooxygenase, lipoxygenase) and cellular targets (macrophages, lymphocytes, epithelial cells, endothelium) have been identified. In addition, many flavonoids display significant antioxidant/radical scavenging properties. There is substantial structural variation in these compounds, which is bound to have an impact on their biological profile, and specifically on their effects on inflammatory conditions. However, in general terms there is substantial consistency in the effects of these compounds despite considerable structural variations. The mechanisms have been studied mainly in myeloid cells, where the predominant effect is an inhibition of NF-κB signaling and the downregulation of the expression of proinflammatory markers. At present there is a gap in knowledge of in vitro and in vivo effects, although the pharmacokinetics of flavonoids has advanced considerably in the last decade. Many flavonoids have been studied for their intestinal antiinflammatory activity which is only logical, since the gastrointestinal tract is naturally exposed to them. However, their potential therapeutic application in inflammation is not restricted to this organ and extends to other sites and conditions, including arthritis, asthma, encephalomyelitis, and atherosclerosis, among others.     

Resveratrol and health--a comprehensive review of human clinical trials

In the past decade, the small polyphenol resveratrol has received widespread attention as either a potential therapy or as a preventive agent for numerous diseases. Studies using purified enzymes, cultured cells, and laboratory animals have suggested that resveratrol has anti-aging, anti-carcinogenic, anti-inflammatory, and anti-oxidant properties that might be relevant to chronic diseases and/or longevity in humans. Although the supporting research in laboratory models is quite substantial, only recently data has emerged to describe the effects of resveratrol supplementation on physiological responses in humans. The limited number of human clinical trials that are available has largely described various aspects of resveratrol's safety and bioavailability, reaching a consensus that it is generally well-tolerated, but have poor bioavailability. Very few published human studies have explored the ability of resveratrol to achieve the physiological benefits that have been observed in laboratory models, although many clinical trials have recently been initiated. This review aims to examine the current state of knowledge on the effects of resveratrol on humans and to utilize this information to develop further guidelines for the implementation of human clinical trials.     

The role of tea and tea flavonoids in cardiovascular health

Consumption of green or black tea has been inversely associated with the development and progression of cardiovascular diseases. In this review, the current knowledge about protective effects of tea and tea constituents, particularly flavonoids, on the cardiovascular system is summarized. Underlying mechanisms for the beneficial effects of tea include vasculoprotective, antioxidative, antithrombogenic, anti-inflammatory, and lipid-lowering properties of tea flavonoids. Although promising experimental data on beneficial effects of tea in various cardiovascular diseases are available, results of clinical studies in humans are not uniform. A number of factors are discussed which may contribute to inconsistent data in humans. Overall, tea represents a promising tool for the prevention and treatment of cardiovascular disorders.     

加工方式对苦荞中黄酮类化合物的影响研究进展

苦荞是传统的食药两用资源,含丰富的营养与功能成分,具有降糖、降脂、降压和抗炎等多种活性,已被开发成各类食品。黄酮类化合物是苦荞中主要的生物活性物质,对人体健康具有促进作用。芦丁和槲皮素是苦荞黄酮类化合物最主要的存在形式,不同加工方式对其含量及转化有显著影响,从而影响苦荞及其相关制品的功能活性和口感;然而目前缺乏相关的系统论述,不利于差异化苦荞健康产品的开发。本文综述了苦荞中黄酮类成分的稳定性和生物转化特性,以及制粉、萌发、发酵、热处理等几种常见加工方式对苦荞中黄酮类成分的影响规律,对苦荞加工过程中黄酮类成分的保持与转化具有重要指导作用,为开发针对性强的苦荞健康制品提供参考。     

食源性抗炎活性肽对肠道炎症的作用研究进展

炎症是机体对感染、伤害或化学刺激引起的防御反应。慢性炎症会反复破坏细胞和组织,从而诱发包括肠道炎症等多种疾病。食源性生物活性肽具有来源广泛、吸收速度快、安全性高等优点,近年来研究发现食源性生物活性肽具有一定的抗炎活性并对维持肠道健康起着积极作用,在炎症性肠病的防治中具有广阔的应用前景。本文就肠道炎症治疗现状,对目前国内外食源性抗炎活性肽的来源、制备、分离纯化、鉴定、抗炎活性评价及作用机制予以综述,并探讨了食源性抗炎活性肽的应用现状,对此研究领域的发展趋势予以展望,旨在为肠道健康功能性食品的研究及开发提供参考。     

Phenolics,inflammation and nutrigenomics

Nutrigenomics is the study of the effects of bioactive compounds from food on gene expression. In the last several years, an increasing body of scientific evidence has demonstrated that individual compounds, as well as complex mixtures of chemicals, derived from food alter the expression of genes in the human body. By turning on or off genes, bioactives in food alter the concentration of specific proteins directly or indirectly associated with human diseases. Several human diseases result in multiple inflammatory responses which are associated with many diseases including arthritis, cancer, cardiovascular disease, dermatitis, asthma, obesity, and others. Detailed mechanisms of action as to how food derived components play an active role in prevention of inflammation have been elucidated. Such biologically active compounds include theaflavins and catechins from tea, curcumin from turmeric, resveratrol from grapes, and lactones from chicory. While chronic diseases are very complex, an opportunity exists to regulate genes involved in inflammation by enriching our diet with the specific foods inherently rich in such compounds, enriched foods containing standardized extracts of well studied sources, or dietary supplements. Copyright © 2006 Society of Chemical Industry