Benefits of polyphenols on gut microbiota and implications in human health

The biological properties of dietary polyphenols are greatly dependent on their bioavailability that, in turn, is largely influenced by their degree of polymerization. The gut microbiota play a key role in modulating the production, bioavailability and, thus, the biological activities of phenolic metabolites, particularly after the intake of food containing high-molecular-weight polyphenols. In addition, evidence is emerging on the activity of dietary polyphenols on the modulation of the colonic microbial population composition or activity. However, although the great range of health-promoting activities of dietary polyphenols has been widely investigated, their effect on the modulation of the gut ecology and the two-way relationship “polyphenols ? microbiota” are still poorly understood.Only a few studies have examined the impact of dietary polyphenols on the human gut microbiota, and most were focused on single polyphenol molecules and selected bacterial populations. This review focuses on the reciprocal interactions between the gut microbiota and polyphenols, the mechanisms of action and the consequences of these interactions on human health.     

森林土壤有机质层中多酚类物质的生态反馈意义

对欧洲中部成熟云杉林分在改造和更新后土壤有机质层中多酚类物质（多酚、缩合单宁）以及与其它化学和生物性质变化的比较,探索了多酚类物质在森林生态系统中的调节功能。结果表明,多酚含量与有效离子交换量（ECEC）呈显著相关性,而与有机含量无显著相关。土壤净矿化率与多酚、有机质C、C/N无显著相关性,而同缩合单宁含量呈显著负相关。同时,土壤多酚含量与土壤可溶性N、C（1mol·L^-1KCl浸提）呈显著正相关。说明多酚类物质虽然在林木自身代谢中没有明显的生理作用,但在整个森林生态系统中的反馈意义应引起重视。     

Are polyphenols antioxidants or pro-oxidants? What do we learn from cell culture and in vivo studies?

Diets rich in polyphenols are epidemiologically associated with lower risk of developing some age-related diseases in humans. This apparent disease-protective effect of polyphenols is often attributed to their powerful antioxidant activities, as established in vitro. However, polyphenols can also exert pro-oxidant activities under certain experimental conditions. Neither pro-oxidant nor anti-oxidant activities have yet been clearly established to occur in vivo in humans, nor are they likely given the limited levels of polyphenols that are achievable in vivo after consumption of foods and beverages rich in them. Other actions of polyphenols may be more important in vivo. Many studies of the biological effects of polyphenols in cell culture have been affected by their ability to oxidise in culture media, and awareness of this problem can avoid erroneous claims.     

Improving the oral bioavailability of beneficial polyphenols through designed synergies

A substantial and growing consumer demand exists for plant-based functional foods that improve general health and wellbeing. Amongst consumed phytochemicals, the polyphenolic compounds tend to be the most bioactive. Many commonly consumed polyphenols have been shown to have specific and potent health-promoting activities when assessed by high-throughput in vitro assays and when administered to experimental animals by injection. However, very few have been shown to have any beneficial effects in animals or man when orally consumed, because of the poor bioavailability exhibited by most polyphenols following the ingestion. Consumed polyphenols, like most pharmaceuticals, are regarded as xenobiotics by the body and must overcome many barriers, including extensive enzymatic and chemical modification during digestion and absorption, to reach their site(s) of action. This is especially true for polyphenols targeting the brain, which is protected by the tightly regulated blood–brain barrier. Interestingly, many polyphenols are also known to specifically modify some of the metabolic and transport processes that govern bioavailability. Therefore, the opportunity exists to increase the bioactivity of beneficial polyphenols by designing specific synergistic interactions with polyphenols that improve their oral bioavailability. This hypothesis and review paper will discuss some of the endogenous systems that limit the bioavailability of ingested polyphenols to the body and the brain, and the means by which bioavailability may be improved by specifically designing synergies between orally consumed polyphenols.     

Antiangiogenic mechanisms of diet-derived polyphenols

Accumulating evidence demonstrates that polyphenols in natural products are beneficial against human lethal diseases such as cancer and metastasis. The underlying mechanisms of anti-cancer effects are complex. Recent studies show that several polyphenols, including epigallocatechin-3-gallate (EGCG) in green tea and resveratrol in red wine, inhibit angiogenesis when administrated orally. These polyphenols have direct effects on suppression of angiogenesis in several standard animal angiogenesis models. Because angiogenesis is involved in many diseases such as cancer, diabetic retinopathy and chronic inflammations, the discovery of these polyphenols as angiogenesis inhibitors has shed light on the health beneficial mechanisms of natural products, which are rich in these molecules. At the molecular level, recent studies have provided important information on how these molecules inhibit endothelial cell growth. Perhaps the greatest therapeutic advantage of these small natural molecules over large protein compounds is that they can be administrated orally without causing severe side effects. It is anticipated that more polyphenols in natural products will be discovered as angiogenesis inhibitors and that these natural polyphenols could serve as leading structures in the discovery of more potent, synthetic angiogenesis inhibitors.     

基于代谢组学的植物多酚及其肠道健康效应研究进展

综述了植物多酚的分类和来源、在代谢组学技术的驱动下,新型多酚物质的鉴定、控制植物多酚合成途径的关键因子以及多酚的功能特性的研究进展,阐述了植物多酚在肠道中的代谢以及其作为“益生元”调节肠道微生态并影响机体健康的重要功能。目前的研究表明不同植物多酚在调节肠道微生态方面存在差异,多数有促进肠道有益菌作用,并通过与肠道微生物“互作”发挥促进健康效应。总之,植物多酚作为“益生元”影响人体健康可能离不开肠道微生物的介导。各个植物多酚的益生功能也需要进一步阐析,在此过程中需要考虑宿主,膳食等混杂因素的综合影响,且需要拓展临床应用方面的研究。     

The effect of enzymatically polymerised polyphenols on CD4 binding and cytokine production in murine splenocytes

High-molecular weight polymerised polyphenols have been shown to exhibit anti-influenza virus, anti-HIV, and anti-cancer activities. The purpose of this study was to evaluate the immunomodulating activities of enzymatically polymerised polyphenols, and to clarify the underlying mechanisms of their effects. The cytokine-inducing activity of the enzymatically polymerised polyphenols derived from caffeic acid (CA), ferulic acid (FA), and p-coumaric acid (CoA) was investigated using murine splenocytes. Polymerised polyphenols, but not non-polymerised polyphenols, induced cytokine synthesis in murine splenocytes. Polymerised polyphenols induced several cytokines in murine splenocytes, with interferon-γ (IFN-γ) and granulocyte-macrophage colony-stimulating factor (GM-CSF) being the most prominent. The underlying mechanisms of the effects of the polymerised polyphenols were then studied using neutralising antibodies and fluorescent-activated cell sorting (FACS) analysis. Our results show that polymerised polyphenols increased IFN-γ and GM-CSF production in splenocytes. In addition, the anti-CD4 neutralised monoclonal antibody (mAb) inhibited polymerised polyphenol-induced IFN-γ and GM-CSF secretion. Moreover, polymerised polyphenols bound directly to a recombinant CD4 protein, and FACS analysis confirmed that interaction occurs between polymerised polyphenols and CD4 molecules expressed on the cell surface. In this study, we clearly demonstrated that enzymatic polymerisation confers immunoactivating potential to phenylpropanoic acids, and CD4 plays a key role in their cytokine-inducing activity.     

Production of concentrated polyphenols by the root cap cells ofCorylus associated withTuber: ultrastructural study and element localization using electron energy loss spectroscopy and imaging

In mycorrhizae, root cap cell differentiation is a rapid event. Dark deposits abruptly invade the cytoplasm and the vacuoles. Finally the vacuoles fill with phenolic deposits and the cytoplasm is moribund. After degradation of the cell wall and cytoplasm, hyphae make contact with polyphenols and penetrate the polyphenols. The polyphenols are incorporated into the fungal mantle. Microanalysis by means of an electron-energy-loss spectrometer (EELS) and an electron imaging system (ESI) reveals the presence of calcium and nitrogen in the polyphenolic material just incorporated into the apical mantle. More distant polyphenols no longer contain calcium but nitrogen is still locally present.     

植物多酚在环境保护与农业生产中的应用

植物多酚是一类广泛存在于植物体内的次生代谢物．自然界含多酚的常见植物已超过600种．随着植物多酚化学结构鉴定及其理化性状的深入研究,人类对植物多酚的应用由传统的化工和医药等领域扩展到了农业和环境等多个领域．文中就植物多酚对植物抗逆境能力以及在环境污染控制和农业生产等领域的应用进行了综述．     

茶多酚的抗氧化和抑菌活性及其增效剂

论述了茶多酚的抗氧化和抑菌活性机理,其中起重要作用的是茶多酚分子内的多个酚羟基。在抗氧化过程中,其酚羟基具有供氢体的活性,阻断自由基的链式反应。在抑菌过程中,其酚羟基可与蛋白质分子中的氨基或羧基结合,其疏水性的苯环结构也可与蛋白质发生疏水结合,茶多酚与蛋白质之间的这种多点结合作用阻止了细菌的侵染,使其具有抑菌性。作为增效剂,有机酸、β-胡萝卜紊等能够增强茶多酚的抗氧化性能;壳聚糖、食盐等能够增强茶多酚的抑菌活性．维生素类既能够增强茶多酚的抗氧化性能又能增强其抑菌作用。     

Structure-dependent interactions of polyphenols with a biomimetic membrane system

Polyphenols are naturally-occurring compounds, reported to be biologically active, and through their interactions with cell membranes. Although association of the polyphenols with the bilayer has been reported, the detailed mechanism of interaction is not yet well elucidated. We report on spatio-temporal real-time membrane dynamics observed in the presence of polyphenols. Two distinct membrane dynamics, corresponding to the two classes of polyphenols used, were observed. Flavonoids (epi-gallocatechin-3-gallate, gallocatechin, theaflavin and theaflavin-3-gallate) caused lipid membrane aggregation and rigidification. As simple structural modification through opening of the aromatic C-ring into an olefin bond, present in trans-stilbenes (resveratrol and picead), completely changed the membrane properties, increasing fluidity and inducing fluctuation. There were differences in the membrane transformations within the same class of polyphenols. Structure-dependent classification of membrane dynamics may contribute to a better understanding of the physicochemical mechanism involved in the bioactivity of polyphenols. In general, an increase in the number of hydrophilic side chains (galloyl, hydroxyl, glucoside, gallate) increased the reactivity of the polyphenols. Most notable was the difference observed through a simple addition of the gallate group. Unraveling the importance of these polyphenols, at a functional group level further opens the key to tailored design of bioactive compounds as potential drug candidates.     

Change in membrane fluidity induced by polyphenols is highly dependent on the position and number of galloyl groups

The cell membrane fluidity was very important in adipogenesis and galloyl groups on polyphenolic structures could enhance their antiadipogenic activity. However, the effect of polyphenols on membrane fluidity and the role of galloyl groups in fluidity changes remain unclear. Therefore, the present study chose structurally different polyphenols to compare their effects on the membrane morphology and fluidity of 3T3-L1 preadipocytes, and then the reasons behind the changes of membrane fluidity induced by galloylated polyphenols were explored from structural and molecular insights using liposome model and molecular dynamic simulation technology. Our results indicated that galloylated polyphenols could significantly change 3T3-L1 cell membrane morphology and decrease membrane fluidity, while non-galloylated ones could not. The membrane interference effect of polyphenols was enhanced as the number of galloyl groups increased. Morever, the decrease in membrane fluidity induced by galloylated polyphenols was due to the disturbance of polyphenols on lipid alkyl chains in the cell membrane. Galloylated polyphenols could not only locate in the polar head, but also insert into hydrophobic center of lipid bilayer to interfere with the lipid alkyl chains arrangement, thus decreasing the membrane fluidity and showing strong affinity for the membrane. In addition, differences in position of galloyl groups in polyphenols induced distinct effect on cell membranes interactions, thus affecting the binding manner and bioactivity. The results expanded the understanding on the strong antiadipogenic activity of galloylated polyphenols through the aspect of their effects on cell membrane by both experimental and theoretically simulated ways.     

Role of peptide primary sequence in polyphenol-protein recognition: an example with neurotensin

Polyphenols are known for their impact on health and one of their major properties is the formation of complexes with proteins. To investigate the involvement of polyphenol-protein complexes in health, the interactions between bioactive polyphenols and neurotensin were examined by structural NMR and molecular modeling. Neurotensin is a linear bioactive tridecapeptide and polyphenols seem to affect the NT metabolism. We studied the polyphenols resveratrol and its glucoside the piceid in order to observe the possible role of glucose group and the penta-O-galloyl-D-glucopyranose (PGG). NMR data and molecular modeling showed that interaction occurred with the three polyphenols involving hydrophobic stacking and hydrogen bonds. Moreover, the peptide primary sequence plays a role in the specificity of complex formation.     

Role of peptide primary sequence in polyphenol–protein recognition: An example with neurotensin

Polyphenols are known for their impact on health and one of their major properties is the formation of complexes with proteins. To investigate the involvement of polyphenol–protein complexes in health, the interactions between bioactive polyphenols and neurotensin were examined by structural NMR and molecular modeling. Neurotensin is a linear bioactive tridecapeptide and polyphenols seem to affect the NT metabolism. We studied the polyphenols resveratrol and its glucoside the piceid in order to observe the possible role of glucose group and the penta-O-galloyl-d-glucopyranose (PGG). NMR data and molecular modeling showed that interaction occurred with the three polyphenols involving hydrophobic stacking and hydrogen bonds. Moreover, the peptide primary sequence plays a role in the specificity of complex formation.     

The involvement of polyphenols and peroxidase activities in heavy-metal accumulation by epidermal glands of the waterlily (Nymphaeaceae)

Co-localization of polyphenols and peroxidase activity was demonstrated in epidermal glands of the waterlily (Nymphaea) by histochemistry. Total phenols, tannins and peroxidase activity were determined quantitatively in plant extracts. Polyphenols were partially identified and were found to consist mainly of hydrolyzable tannins, gallic and tannic acid derivatives.Nymphaea polyphenols were shown to chelate Cr, Hg, and Pb in vitro, and Cd-binding by polymerized polyphenols was demonstrated in leaves exposed to Cd in vivo. Both polyphenols and peroxidases were found at very high constitutive levels, which were not induced or altered by external conditions, such as light and heavy-metal stress. It is suggested that the polymerization of polyphenols by peroxidases, enhanced after heavy-metal uptake and detoxification, is responsible for the binding of heavy metals in Nymphaea epidermal glands. Received: 29 April 2000 / Accepted: 8 June 2000     

Potential Role of Naturally Derived Polyphenols and Their Nanotechnology Delivery in Cancer

Polyphenols are natural compounds found in plants, fruits, chocolate, and beverages such as tea and wine. To date, the majority of polyphenol research shows them to have anticancer activity in cell lines and animal models. Some human clinical trials also indicate possible anticancer benefits are associated with polyphenols. A problem with polyphenols is their short half-life and low bioavailability; thus the use of nanoparticles to enhance their delivery is a new research field. A Pubmed search was conducted to find in vitro, in vivo, and human clinical trials done within the past 10 years involving the use of polyphenols against different cancer types, and for studies done within the past 5 years on the use of nanoparticles to enhance polyphenol delivery. Based on the studies found, it is observed that polyphenols may be a potential alternative or additive therapy against cancer, and the use of nanoparticles to enhance their delivery to tumors is a promising approach. However, further human clinical trials are necessary to better understand the use of polyphenols as well as their nanoparticle-mediated delivery.     

Polyphenols in cerebral ischemia

Plant polyphenols are dietary components that exert a variety of biochemical and pharmacological effects. Recently, considerable interest has been focused on polyphenols because of their antioxidant, anti-inflammatory, and antiproliferative activities. Oxidative stress is thought to be a key event in the pathogenesis of cerebral ischemia. Overproduction of reactive oxygen species during ischemia/reperfusion could cause an imbalance between oxidative and antioxidative processes. Reactive oxygen species can damage lipids, proteins, and nucleic acids, thereby inducing apoptosis or necrosis. There is increasing evidence supporting the hypothesis that plant polyphenols can provide protection against neurodegenerative changes associated with cerebral ischemia. This article reviews the neuroprotective effects of plant extracts and their constituents that have been used in animal models of cerebral ischemia. The use of polyphenols as therapeutic agents in stroke has been suggested.     

Green tea polyphenols enhance sodium nitroprusside-induced neurotoxicity in human neuroblastoma SH-SY5Y cells

Oxidative stress is a main mediator in nitric oxide (NO) -induced neurotoxicity and has been implicated in the pathogenesis of many neurodegenerative disorders. Green tea polyphenols are usually expected as potent chemo-preventive agents due to their ability of scavenging free radicals and chelating metal ions. However, not all the actions of green tea polyphenols are necessarily beneficial. In the present study, we demonstrated that higher-concentration green tea ployphenols significantly enhanced the neurotoxicity by treatment of sodium nitroprusside (SNP), a nitric oxide donor. SNP induced apoptosis in human neuroblastoma SH-SY5Y cells in a concentration and time-dependent manner, as estimated by cell viability assessment, FACScan analysis and DNA fragmentation assay, whereas treatment with green tea polyphenols alone had no effect on cell viability. Pre-treatment with lower-dose green tea polyphenols (50 and 100 microm) had only a slightly deleterious effect in the presence of SNP, while higher-dose green tea polyphenols (200 and 500 microm) synergistically damaged the cells severely. Further research showed that co-incubation of green tea polyphenols and SNP caused loss of mitochondrial membrane potential, depletion of intracellular GSH and accumulation of reactive oxygen species, and exacerbated NO-induced neuronal apoptosis via a Bcl-2 sensitive pathway.     

茶多酚提取方法的研究进展

茶多酚是一种理想的食品天然抗氧化剂,具有抗癌治病、防衰老、防辐射、消除人体自由基等多种生理功效,广泛用于食品、油脂、医药、化工等行业。近年来,对于茶多酚的提取方法多见于报遗,本文就国内外茶多酚提取方法的研究进展情况作以综述。