共查询到20条相似文献,搜索用时 15 毫秒
1.
《Phytomedicine》2021
BackgroundEpidemiological studies has revealed that a diet rich in fruits and vegetables could lower the risk of certain cancers. In this setting, natural polyphenols are potent anticancer bioactive compounds to overcome the non-target specificity, undesirable cytotoxicity and high cost of treatment cancer chemotherapy.PurposeThe review focuses on diverse classifications of the chemical diversity of dietary polyphenol and their molecular targets, modes of action, as well as preclinical and clinical applications in cancer prevention.ResultsThe dietary polyphenols exhibit chemo-preventive activity through modulation of apoptosis, autophagy, cell cycle progression, inflammation, invasion and metastasis. Polyphenols possess strong antioxidant activity and control multiple molecular events through activation of tumor suppressor genes and inhibition of oncogenes involved in carcinogenesis. Numerous in vitro and in vivo studies have evidenced that these dietary phytochemicals regulate critical molecular targets and pathways to limit cancer initiation and progression. Moreover, natural polyphenols act synergistically with existing clinically approved drugs. The improved anticancer activity of combinations of polyphenols and anticancer drugs represents a promising perspective for clinical applications against many human cancers.ConclusionThe anticancer properties exhibited by dietary polyphenols are mainly attributed to their anti-metastatic, anti-proliferative, anti-angiogenic, anti-inflammatory, cell cycle arrest, apoptotic and autophagic effects. Hence, regular consumption of dietary polyphenols as food or food additives or adjuvants can be a promising tactic to preclude adjournment or cancer therapy. 相似文献
2.
Recent clinical and epidemiological researches have declared that non-steroidal anti-inflammatory agents may display as antineoplastic agents and indicate pro-apoptotic and antiproliferative effects on cancer cells. The major purpose of this research was to develop a novel poly(ethyleneglycol)-block-poly(ε-caprolactone) (PEG-b-PCL) nano-sized particles encapsulated with nimesulide (NMS), a selective COX-2 inhibitor, and to evaluate its anticancer activity against MCF-7 breast cancer cells. NMS-encapsulated PEG-b-PCL nanoparticles were fabricated using three different production techniques: (i) by emulsion-solvent evaporation using a high shear homogenizer, (ii) by emulsion-solvent evaporation using an ultrasonicator, and (iii) by nanoprecipitation. Nanoparticles were evaluated with respect to the entrapment efficiency, size characteristics, drug release rates, thermal behavior, cell viability assays, and apoptosis. The resulting nanoparticles were found to be spherical shapes with negative surface charges. The average diameter of all nanoparticles ranged between 148.5 and 307.2 nm. In vitro release profiles showed that all nanoparticles exhibited a biphasic release pattern. NMS-loaded PEG-b-PCL nanoparticles demonstrated significant anticancer activity against MCF-7 breast cancer cells in a dose-dependent manner, and the effects of nanoparticles on cell proliferation were significantly affected by the preparation techniques. The nanoparticles developed in this work displayed higher potential for the NMS delivery against breast cancer treatment for the future. 相似文献
3.
4.
Hussin A. Rothan Zulqarnain Mohamed Pottayil G. Sasikumar Ketha Amarnadh Reddy Noorsaadah Abd Rahman Rohana Yusof 《International journal of peptide research and therapeutics》2014,20(3):259-267
Even with the great advances in cancer therapies, cancer remains the major cause of death worldwide. The use of high doses of anti-cancer chemotherapeutic drugs eventually causes the inevitable damage in non-neoplastic cells. New, selective, and more effective drugs are therefore urgently required to fight cancer. In this study, the anticancer activity of new peptide analogues (P1 and P2) derived from natural peptide, protegrin-1 (PG-1) were evaluated against human breast carcinoma cell lines (MCF-7) and human non-neoplastic mammary epithelial cell lines (MCF-10A), human hepatocellular carcinoma cells (HepG2) and Vero cells. The CC50 values of cancer cells were significantly lower (P < 0.01) compared to non-neo-plastic cells after treating with P1 and P2 analogues. The analogues of PG-1 showed lower percentage of Lactate Dehydrogenase release (P < 0.001) from non-neoplastic cells compared to cancer cells and low haemolytic potential (P < 0.001) compared to PG-1. The P1 and P2 analogues were shown to be able to induce cancer cell senescence and apoptosis in a p53-dependent pathway which in turn, induced caspase activities and subsequent cell death. Overall, these results suggested that designing shorter peptides, as well as altering the number and position of positive charged residues in P1 and P2 analogues resulted in reduction of their toxicity to non-neoplastic cells and increased selectivity towards cancer cells. Increased selectivity also suggests its potential use to be developed as delivery vectors in the design of chemotherapeutic anticancer drugs. 相似文献
5.
《Saudi Journal of Biological Sciences》2021,28(10):5674-5683
The agricultural wastes adversely affect the environment; however, they are rich in polyphenols; therefore, this study aimed to employ polyphenol-enriched waste extracts for silver nanoparticles synthesis, and study the larvicidal activity of silver nanoparticles fabricated by pomegranate and watermelon peels extracts (PPAgNPs and WPAgNPs) against all larval instars of Spodoptera littoralis. The polyphenol profile of pomegranate and watermelon peel extracts (PP and WP) and silver nanoparticles was detected by HPLC. The antioxidant activity was estimated by DPPH, and FARP assays and the antimicrobial activity was evaluated by disc assay. The Larvicidal activity of AgNPs against Egyptian leaf worm was performed by dipping technique. The obtained AgNPs were spherical with size ranged 15–85 nm and capped with proteins and polyphenols. The phenolic compounds in silver nanoparticles increased about extracts; therefore, they have the best performance in antioxidant/reducing activity, and inhibit the growth of tested bacteria and yeast. The PPAgNPs were the most effective against the first instar larvae instar (LC50 = 68.32 µg/ml), followed by pomegranate extract with (LC50 = 2852 µg/ml). The results indicated that obvious increase in polyphenols content in silver nanoparticles enhance their larvicidal effect and increasing mortality of 1st larval of S. littoralis Egyptian leafworms causing additive effect and synergism. We recommend recycling phenolic enriched agricultural wastes in producing green silver nanoprticles to control cotton leafworm that causes economic loses to crops. 相似文献
6.
S. Vijaya Laxmi P. Anil G. Rajitha Asha Jyothi Rao Peter A. Crooks B. Rajitha 《Journal of chemical biology》2016,9(4):97-106
In the search of efficient anticancer agents, here, new 5-(4-alkylbenzyledene)thiazolidine-2,4-dione derivatives (5a–g) have been successfully synthesized and characterized and are evaluated for anticancer and antimicrobial activities using DNA cleavage studies. In vitro studies on anticancer activity of compound 5d (NSC: 768619/1) was done against the full panel of 60 human tumor cell lines. The five-level dose activity results revealed that, the compound 5d was active against all the cell lines, it has shown potential activity against leukemia SR (GI50: 2.04 μM), non-small cell lung cancer NCI-H522 (GI50: 1.36 μM), colon cancer COLO 205 (GI50: 1.64 μM), CNS cancer SF-539 (GI50: 1.87 μM), melanoma SK-MEL-2 (GI50: 1.64 μM), ovarian cancer OVCAR-3 (GI50: 1.87 μM), renal cancer RXF 393 (GI50: 1.15 μM), prostate cancer PC-3 (GI50: 1.90 μM), and breast cancer MDA-MB-468(GI50: 1.11 μM). DNA cleavage studies revealed that at 50 μg/mL concentration, partial DNA digestion was observed and when the concentration is increasing to threefold (150 μg/mL), complete linear DNA digestion and partial supercoiled DNA digestion was observed. Further antimicrobial studies indicate that all the synthesized compounds except compound 5a possess prominent activity against all the screened microbial species. This study throws a ray of light in the field of anticancer drugs. 相似文献
7.
Current cancer management strategies fail to adequately treat malignancies with multivariable dose-restricting factors such as systemic toxicity and multi-drug resistance limiting therapeutic benefit, quality of life and complete long-term remission rates. The targeted delivery of a therapeutic compound aims to enhance its circulation and cellular uptake, decrease systemic toxicity and improve therapeutic benefit with disease specificity. The transferrin peptide, its receptor and their biological significance, has been widely characterised and vastly relevant when applied to targeting strategies. Utilising knowledge about the physiological function of the transferrin–transferrin receptor complex and the efficiency of its receptor-mediated endocytosis provides rationale to continue the development of transferrin-targeted anticancer modalities. Furthermore, multiple studies report an upregulation in expression of the transferrin receptor on metastatic and drug resistant tumours, highlighting its selectivity to cancer. Due to the increased expression of the transferrin receptor in brain glioma, the successful delivery of anticancer compounds to the tumour site and the ability to cross the blood brain barrier has shown to be an important discovery. Its significance in the development of cancer-specific therapies is shown to be important by direct conjugation and immunotoxin studies which use transferrin and anti-transferrin receptor antibodies as the targeting moiety. Such conjugates have demonstrated enhanced cellular uptake via transferrin-mediated mechanisms and increased selective cytotoxicity in a number of cancer cell lines and tumour xenograft animal models. In addition, incubation of chemotherapy-insensitive cancer cells with transferrin-targeted conjugates in vitro has resulted in a reversal of their drug resistance. Transferrin immunotoxins have also shown similar promise, with a diphtheria toxin mutant covalently bound to transferrin (Tf-CRM107) currently involved in human clinical trials for the treatment of glioblastoma. Despite this, the inability to translate preliminary research into a clinical setting has compelled research into novel targeting strategies including the use of nanoparticulate theory in the design of drug delivery systems. The main objective of this review is to evaluate the importance of the transferrin–transferrin receptor complex as a target for cancer therapy through extensive knowledge of both the physiological and pathological interactions between the complex and different cell types. In addition, this review serves as a summary to date of direct conjugation and immunotoxin studies, with an emphasis on transferrin as an important targeting moiety in the directed delivery of anticancer therapeutic compounds. 相似文献
8.
《生物化学与生物物理学报:癌评论》2023,1878(2):188862
Despite the remarkable advancement in the health care sector, cancer remains the second most fatal disease globally. The existing conventional cancer treatments primarily include chemotherapy, which has been associated with little to severe side effects, and radiotherapy, which is usually expensive. To overcome these problems, target-specific nanocarriers have been explored for delivering chemo drugs. However, recent reports on using a few proteins having anticancer activity and further use of them as drug carriers have generated tremendous attention for furthering the research towards cancer therapy. Biomolecules, especially proteins, have emerged as suitable alternatives in cancer treatment due to multiple favourable properties including biocompatibility, biodegradability, and structural flexibility for easy surface functionalization. Several in vitro and in vivo studies have reported that various proteins derived from animal, plant, and bacterial species, demonstrated strong cytotoxic and antiproliferative properties against malignant cells in native and their different structural conformations. Moreover, surface tunable properties of these proteins help to bind a range of anticancer drugs and target ligands, thus making them efficient delivery agents in cancer therapy. Here, we discuss various proteins obtained from common exogenous sources and how they transform into effective anticancer agents. We also comprehensively discuss the tumor-killing mechanisms of different dietary proteins such as bovine α-lactalbumin, hen egg-white lysozyme, and their conjugates. We also articulate how protein nanostructures can be used as carriers for delivering cancer drugs and theranostics, and strategies to be adopted for improving their in vivo delivery and targeting. We further discuss the FDA-approved protein-based anticancer formulations along with those in different phases of clinical trials. 相似文献
9.
Gambogic acid (GA) has been proven to be a potent chemotherapeutic agent for the treatment of lung cancer in clinical trials. However, GA is limited in its therapeutic value by properties such as poor water solubility and low chemical stability. In clinical trials, cationic arginine (Arg) was added to solubilize GA, and this may also cause other side effects. Here, we have designed and developed a more efficient human serum albumin (HSA)-based delivery system for GA with low toxicity which helps improve its solubility, chemical stability and increases its antitumor efficacy. The GA-HSA nanoparticles (NPs) were prepared by albumin-bound (nabTM) technology, with a particle size of 135.2?±?35.03 nm, a zeta potential of ?21.81?±?1.24 mV, and a high entrapment efficiency. Compared with GA-Arg solution, the physical and chemical stability of the NPs were improved when stored at pH 7.4 in PBS or freeze-dried. The in vitro drug release showed that GA-HSA NPs had a more sustained release than GA-Arg solution. Furthermore, HSA NPs improved the therapeutic efficacy of GA and were less toxic compared with GA-Arg solution in A549-bearing mice. Therefore, this delivery system is a promising polymeric carrier for GA when used for tumor therapy. 相似文献
10.
Polyphenols as antimicrobial agents 总被引:2,自引:0,他引:2
Daglia M 《Current opinion in biotechnology》2012,23(2):174-181
Polyphenols are secondary metabolites produced by higher plants, which play multiple essential roles in plant physiology and have potential healthy properties on human organism, mainly as antioxidants, anti-allergic, anti-inflammatory, anticancer, antihypertensive, and antimicrobial agents. In the present review the antibacterial, antiviral, and antifungal activities of the most active polyphenol classes are reported, highlighting, where investigated, the mechanisms of action and the structure-activity relationship. Moreover, considering that the microbial resistance has become an increasing global problem, and there is a compulsory need to find out new potent antimicrobial agents as accessories to antibiotic therapy, the synergistic effect of polyphenols in combination with conventional antimicrobial agents against clinical multidrug-resistant microorganisms is discussed. 相似文献
11.
In this review we discuss features of mRNA synthesis and modifications used to minimize immune response and prolong efficiency of the translation process in vivo. Considerable attention is given to the use of liposomes and nanoparticles containing lipids and polymers for the mRNA delivery. Finally we briefly discuss mRNAs which are currently in the clinical trials for cancer immunotherapy, vaccination against infectious diseases, and replacement therapy. 相似文献
12.
This study described a simple and green approach for the synthesis of silver nanoparticles (AgNPs) employing benzoin gum water extract as a reducing and capping agent and their applications. The AgNPs were characterized by ultraviolet–visible spectrophotometer, X-ray diffraction pattern, field emission transmission electron microscopy, dynamic light scattering, zeta potential and fourier transform infrared spectroscopy. The AgNPs showed promising antimicrobial activity against various pathogens (Gram-negative, Gram-positive and fungus) and possessed high free radical scavenging activity (104.5 ± 7.21 % at 1 mg/ml). In addition, the AgNPs exhibited strong cytotoxicity towards human cervical cancer and human lung cancer cells as compared to the normal mouse macrophage cells. Moreover, the AgNPs possessed anti-biofilm activity against Escherichia coli, and compatibility to human keratinocyte HaCaT cells, which suggests the use of dressing with the AgNPs in chronic wound treatment. Therefore, AgNPs synthesized by benzoin gum extract are comparatively green and may have broad spectrum potential application in biomedicine. 相似文献
13.
Recent advances have been made in cancer chemotherapy through the development of conjugates for anticancer drugs. Many drugs have problems of poor stability, water insolubility, low selectivity, high toxicity, and side effects. Most of the chitosan nanoparticles showed to be good drug carriers because of their biocompatibility, biodegradability, and it can be readily modified. The anticancer drug with chitosan nanoparticles displays efficient anticancer effects with a decrease in the adverse effects of the original drug due to the predominant distribution into the tumor site and a gradual release of free drug from the conjugate which enhances drug solubility, stability, and efficiency. In this review, we discuss wider applications of numerous modified chitosan nanoparticles against different tumors and also focusing on the administration of anticancer drugs through various routes. We propose the interaction between nanosized drug carrier and tumor tissue to understand the synergistic interplay. Finally, we elaborate merits of drug delivery system at the tumor site, with emphasizing future challenges in cancer chemotherapy. 相似文献
14.
Flavonoids are polyphenolic compounds widely distributed in the plant kingdom. Compelling research indicates that flavonoids have important roles in cancer chemoprevention and chemotherapy possibly due to biological activities that include action through anti-inflammation, free radical scavenging, modulation of survival/proliferation pathways, and inhibition of the ubiquitin-proteasome pathway. Plant polyphenols including the green tea polyphenol (-)-epigallocatechin gallate or (-)-EGCG, and the flavonoids apigenin, luteolin, quercetin, and chrysin have been shown to inhibit proteasome activity and induce apoptosis in human leukemia cells. However, biotransformation reactions to the reactive hydroxyl groups on polyphenols could reduce their biological activities. Although methylated polyphenols have been suggested to be metabolically more stable than unmethylated polyphenols, the practical use of methylated polyphenols as cancer preventative agents warrants further investigation. In the current study, methylated and unmethylated flavonoids were studied for their proteasome-inhibitory and apoptosis-inducing abilities in human leukemia HL60 cells. Methylated flavonoids displayed sustained bioavailability and inhibited cellular proliferation by arresting cells in the G(1) phase. However, they did not act as proteasome inhibitors in either an in vitro system or an in silico model and only weakly induced apoptosis. In contrast, unmethylated flavonoids exhibited inhibition of the proteasomal activity in intact HL60 cells, accumulating proteasome target proteins and inducing caspase activation and poly(ADP-ribose) polymerase cleavage. We conclude that methylated flavonoids lack potent cytotoxicity against human leukemia cells and most likely have limited ability as chemopreventive agents. 相似文献
15.
Shichao Wu Xiangrui Yang Fanghong Luo Ting Wu Peilan Xu Mingyuan Zou Jianghua Yan 《Journal of nanobiotechnology》2018,16(1):90
Background
In the last decade, the biosynthesis of metal nanoparticles using organisms have received more and more considerations. However, the complex composition of organisms adds up to a great barrier for the characterization of biomolecules involved in the synthesis process and their biological mechanisms.Results
In this research, we biosynthesized a kind of flower-shaped Au nanoclusters (Au NCs) using one definite component—epigallocatechin gallate (EGCG), which was the main biomolecules of green tea polyphenols. Possessing good stability for 6 weeks and a size of 50 nm, the Au NCs might be a successful candidate for drug delivery. Hence, both methotrexate (MTX) and doxorubicin (DOX) were conjugated to the Au NCs through a bridge of cysteine (Cys). The introduction of MTX provided good targeting property for the Au NCs, and the conjugation of DOX provided good synergistic effect. Then, a novel kind of dual-drug loaded, tumor-targeted and highly efficient drug delivery system (Au-Cys-MTX/DOX NCs) for combination therapy was successfully prepared. The TEM of HeLa cells incubated with Au-Cys-MTX/DOX NCs indicated that the Au-Cys-MTX/DOX NCs could indeed enter and kill cancer cells. The Au-Cys-MTX/DOX NCs also possessed good targeting effect to the FA-receptors-overpressed cancer cells both in vitro and in vivo. Importantly, the Au-Cys-MTX/DOX NCs resulted in an excellent anticancer activity in vivo with negligible side effects.Conclusions
These results suggest that the biosynthesized Au-Cys-MTX/DOX NCs could be a potential carrier with highly efficient anticancer properties for tumor-targeted drug delivery.16.
Resveratrol (3,4',5-trihydroxy stilbene), a plant derived polyphenol found in mulberries, grapes and red wine is considered to possess chemopreventive properties against cancer. It is recognized as a naturally occurring antioxidant but also catalyzes oxidative DNA degradation in vitro in the presence of transition metal ions such as copper. Using a cellular system of lymphocytes isolated from human peripheral blood and Comet assay, we have confirmed that resveratrol-Cu(II) system is indeed capable of causing DNA degradation in cells such as lymphocytes. Also, trans-stilbene, which does not have any hydroxyl groups, is inactive in the lymphocyte system. Pre-incubation of lymphocytes with resveratrol indicates that it is capable of either traversing the cell membrane or binding to it. Our results are in partial support of our hypothesis that anticancer properties of various plant derived polyphenols may involve mobilization of endogenous copper and the consequent prooxidant action. 相似文献
17.
P. Chanphai 《Journal of biomolecular structure & dynamics》2013,31(13):3487-3495
Dietary polyphenols are abundant micronutrients in our diet and paly major role in prevention of degenerative diseases. The binding efficacy of antioxidant polyphenols resveratrol, genistein, and curcumin with PAMAM-G3 and PAMAM-G4 nanoparticles was investigated in aqueous solution at physiological conditions, using multiple spectroscopic methods, TEM images, and docking studies. The polyphenol bindings are via hydrophilic, hydrophobic, and H-bonding contacts with resveratrol forming more stable conjugates. As PAMAM size increased the loading efficacy and the stability of polyphenol-polymer conjugates were increased. Polyphenol binding induced major alterations of dendrimer morphology. PAMAM nanoparticles are capable of delivery of polyphenols in vitro. 相似文献
18.
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。 相似文献
19.
Athina Angelopoulou Efstathia Voulgari Argiris Kolokithas-Ntoukas Aristides Bakandritsos Konstantinos Avgoustakis 《AAPS PharmSciTech》2018,19(2):621-633
In solid tumors, hypoxia (lack of oxygen) is developed, which leads to the development of resistance of tumor cells to chemotherapy and radiotherapy through various mechanisms. Nevertheless, hypoxic cells are particularly vulnerable when glycolysis is inhibited. For this reason, in this study, the development of magnetically targetable nanocarriers of the sodium-glucose transporter protein (SGLT2) inhibitor dapagliflozin (DAPA) was developed for the selective delivery of DAPA in tumors. This nanomedicine in combination with radiotherapy or chemotherapy should be useful for effective treatment of hypoxic tumors. The magnetic nanoparticles consisted of a magnetic iron oxide core and a poly(methacrylic acid)-graft-poly(ethyleneglycol methacrylate) (PMAA-g-PEGMA) polymeric shell. The drug (dapagliflozin) molecules were conjugated on the surface of these nanoparticles via in vivo hydrolysable ester bonds. The nanoparticles had an average size of ~ 70 nm and exhibited a DAPA loading capacity 10.75% (w/w) for a theoretical loading 21.68% (w/w). The magnetic responsiveness of the nanoparticles was confirmed with magnetophoresis experiments. The dapagliflozin-loaded magnetic nanoparticles exhibited excellent colloidal stability in aqueous and biological media. Minimal (less than 15% in 24 h) drug release from the nanoparticles occurred in physiological pH 7.4; however, drug release was significantly accelerated in pH 5.5. Drug release was also accelerated (triggered) under the influence of an alternating magnetic field. The DAPA-loaded nanoparticles exhibited higher in vitro anticancer activity (cytotoxicity) against A549 human lung cancer cells than free DAPA. The application of an external magnetic field gradient increased the uptake of nanoparticles by cells, leading to increased cytotoxicity. The results justify further in vivo studies of the suitability of DAPA-loaded magnetic nanoparticles for the treatment of hypoxic tumors. 相似文献
20.
Role of plant polyphenols in genomic stability 总被引:19,自引:0,他引:19
Ferguson LR 《Mutation research》2001,475(1-2):89-111
Polyphenols are a large and diverse class of compounds, many of which occur naturally in a range of food plants. The flavonoids are the largest and best-studied group of these. A range of plant polyphenols are either being actively developed or currently sold as dietary supplements and/or herbal remedies. Although, these compounds play no known role in nutrition (non-nutrients), many of them have properties including antioxidant, anti-mutagenic, anti-oestrogenic, anti-carcinogenic and anti-inflammatory effects that might potentially be beneficial in preventing disease and protecting the stability of the genome. However not all polyphenols and not all actions of individual polyphenols are necessarily beneficial. Some have mutagenic and/or pro-oxidant effects, as well as interfering with essential biochemical pathways including topoisomerase enzyme activities, prostanoid biosynthesis and signal transduction. There is a very large amount of in vitro data available, but far fewer animal studies, and these are not necessarily predictive of human effects because of differences in bacterial and hepatic metabolism of polyphenols between species. Epidemiological studies suggest that high green tea consumption in the Japanese population and moderate red wine consumption in the French population may be beneficial for heart disease and cancer, and these effects may relate to specific polyphenols. A small number of adequately controlled human intervention studies suggest that some, but not all polyphenol extracts or high polyphenol diets may lead to transitory changes in the antioxidative capacity of plasma in humans. However, none of these studies have adequately considered long-term effects on DNA or the chromosome and unequivocally associated these with polyphenol uptake. Furthermore, clinical trials have required intravenously administered polyphenols at concentrations around 1400mg/m(2) before effects are seen. These plasma concentrations are unlikely to be achieved using the dietary supplements currently available. More focused human studies are necessary before recommending specific polyphenolic supplements at specific doses in the human population. 相似文献