DOCSLIB.ORG

Role of Resveratrol in Prevention and Therapy of Cancer: Preclinical and Clinical Studies

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Role of Resveratrol in Prevention and Therapy of Cancer: Preclinical and Clinical Studies ANTICANCER RESEARCH 24: 2783-2840 (2004) Review Role of Resveratrol in Prevention and Therapy of Cancer: Preclinical and Clinical Studies BHARAT B. AGGARWAL1, ANJANA BHARDWAJ1, RISHI S. AGGARWAL1, NAVINDRA P. SEERAM2, SHISHIR SHISHODIA1 and YASUNARI TAKADA1 1Cytokine Research Laboratory, Department of Bioimmunotherapy, The University of Texas M. D. Anderson Cancer Center, Box 143, 1515 Holcombe Boulevard, Houston, Texas 77030; 2UCLA Center for Human Nutrition, David Geffen School of Medicine, 900 Veteran Avenue, Los Angeles, CA 90095-1742, U.S.A. Abstract. Resveratrol, trans-3,5,4'-trihydroxystilbene, was first and cervical carcinoma. The growth-inhibitory effects of isolated in 1940 as a constituent of the roots of white hellebore resveratrol are mediated through cell-cycle arrest; up- (Veratrum grandiflorum O. Loes), but has since been found regulation of p21Cip1/WAF1, p53 and Bax; down-regulation of in various plants, including grapes, berries and peanuts. survivin, cyclin D1, cyclin E, Bcl-2, Bcl-xL and cIAPs; and Besides cardioprotective effects, resveratrol exhibits anticancer activation of caspases. Resveratrol has been shown to suppress properties, as suggested by its ability to suppress proliferation the activation of several transcription factors, including NF- of a wide variety of tumor cells, including lymphoid and Î B, AP-1 and Egr-1; to inhibit protein kinases including IÎ B· myeloid cancers; multiple myeloma; cancers of the breast, kinase, JNK, MAPK, Akt, PKC, PKD and casein kinase II; prostate, stomach, colon, pancreas, and thyroid; melanoma; and to down-regulate products of genes such as COX-2, head and neck squamous cell carcinoma; ovarian carcinoma; 5-LOX, VEGF, IL-1, IL-6, IL-8, AR and PSA. These Correspondence to: Bharat B. Aggarwal, Cytokine Research growth factor receptor; HUVEC, human umbilical vein endothelial Laboratory, Department of Bioimmunotherapy, The University of cells; 8-OHdG, 8-hydroxydeoxyguanosine; TBARS, thiobarbituric acid- Texas M. D. Anderson Cancer Center, Box 143, 1515 Holcombe reactive substances; AAPH, 2,2'-azobis-(2-amidinopropane) Boulevard, Houston, Texas 77030, U.S.A. Tel: 713-792-3503/6459, dihydrochloride; IC50, concentration causing 50% inhibition; ICV, Fax: 713-794-1613, e-mail: [email protected] intracerebroventricular; STZ, streptozotocin; HMG, half-mustard gas; LLC, Lewis lung carcinoma; VEGF, vascular endothelial growth factor; Key Words: Resveratrol, cell signaling, chemoprevention, metastasis, BHA, butylated hydroxyanisole; ICAM, intracellular adhesion transformation, invasion, tumorigenesis, apoptosis, review. molecule; VCAM, vascular cell adhesion molecule; MMP, matrix metalloproteinase; IL, interleukin; PARP, poly(ADP-ribose) Abbreviations: TNF, tumor necrosis factor; NF-Î B, nuclear factor kappa polymerase; Egr, early growth response gene; ER, estrogen receptor; B; PKC, protein kinase C; UV, ultraviolet; NOS, nitric oxide synthase; CYP, cytochrome P450; IFN, interferon; NSAID, nonsteroidal anti- COX, cyclooxygenase; PMA, phorbol myristate acetate; LDL, low- inflammatory drug; H2O2, hydrogen peroxide; Cdk; cyclin-dependent density lipoprotein; PBMC, peripheral blood mononuclear cells; PMN, kinases; PDGF, platelet-derived growth factor; PSA, prostate-specific human polymorphonuclear leukocytes; GSH, reduced glutathione; AP-1, antigen; ACF, aberrant crypt foci; Ach, acetylcholine; MDA, activator protein-1; MAPK, mitogen-activated protein kinase; ERK, malondialdehyde; SHRSP, stroke-prone hypertensive rats; Ïmax, extracellular signal-regulated kinase; TGF, transforming growth factor; wavelength maxima; HPLC, high-pressure (performance) liquid PKA, protein kinase A; DMBA, 7,12-dimethylbenzoic acid; B[a]P, chromatography; MS, mass spectrometric; CoA, coenzyme A; NO, benzo[·]pyrene; BPDE, B[a]P diol epoxides; AhR, aryl hydrocarbon nitric oxide; AIF, apoptosis-inducing factor; AML, acute myeloid receptor; PhiP, 2-amino1-methyl-6-phenylimidazo[4,5-b]pyridine; AOM, leukemia; DISC, death-inducing signal complex; AR, androgen azoxymethane; NNK, 4-(methyl-nitrososamine)-1-(3-pyridyl)-1-butanone; receptor; ALL, acute lymphocytic leukemia; Rb, retinoblastoma; SPT, ODC, ornithine decarboxylase; B-CLL, B-cell chronic lymphocytic serine palmitoyltransferase; PDE, phosphodiesterase; AZT, leukemia; CTL, cytotoxic T lymphocyte; NQO, NAD(P)H quinone zidovudine; ddC, zalcitabine; ddI, didanosine; PKD, protein kinase D; oxidoreductase; HMG-CoA, 3-hydroxy-3-methylglutaryl coenzyme A; LPS, lipopolysaccharide; PI3K, phosphoinositide 3-kinase; TRAIL, SBP, systolic blood pressure; EWP, extract of wine phenolics ; SMC, tumor necrosis factor-related apoptosis-inducing ligand; FADD, Fas- smooth muscle cells; ROS, reactive oxygen species; EGFR, epidermal associated death domain. 0250-7005/2004 $2.00+.40 2783 ANTICANCER RESEARCH 24: 2783-2840 (2004) activities account for the suppression of angiogenesis by this C1h. Suppression of NO/NOS by resveratrol stilbene. Resveratrol also has been shown to potentiate the C1i. Suppression of growth factor protein tyrosine kinases apoptotic effects of cytokines (e.g., TRAIL), chemotherapeutic by resveratrol agents and Á-radiation. Phamacokinetic studies revealed that C1j. Suppression of COX-2 and lipooxygenase by the target organs of resveratrol are liver and kidney, where it is resveratrol concentrated after absorption and is mainly converted to a C1k. Suppression of cell-cycle proteins by resveratrol sulfated form and a glucuronide conjugate. In vivo, resveratrol C1l. Suppression of adhesion molecules by resveratrol blocks the multistep process of carcinogenesis at various C1m. Suppression of androgen receptors by resveratrol stages: it blocks carcinogen activation by inhibiting aryl C1n. Suppression of PSA by resveratrol hydrocarbon-induced CYP1A1 expression and activity, and C1o. Suppression of inflammatory cytokine expression by suppresses tumor initiation, promotion and progression. resveratrol Besides chemopreventive effects, resveratrol appears to exhibit C1p. Suppression of angiogenesis, invasion and metastasis therapeutic effects against cancer. Limited data in humans by resveratrol have revealed that resveratrol is pharmacologically quite safe. C1q. Effect of resveratrol on bone cells Currently, structural analogues of resveratrol with improved C1r. Effects of resveratrol on expression of cytochrome bioavailability are being pursued as potential therapeutic p450 and metabolism of carcinogens agents for cancer. C1s. Suppression of inflammation by resveratrol C1t. Antioxidant effects of resveratrol Contents C1u. Suppression of transformation by resveratrol C1v. Induction of cellular differentiation by resveratrol Introduction C1w. Estrogenic/antiestrogenic effects of resveratrol A. Source of resveratrol C1x. Effect of resveratrol on normal cells B. Chemistry of resveratrol C1y. Suppression of mutagenesis by resveratrol C. Preclinical Studies C1z. Radioprotective and radiosensitive effect of resveratrol C1. In vitro effects C1aa. Chemosensitization by resveratrol C1a. Antiproliferative effects of resveratrol C1ab. Direct targets of resveratrol B-cell lymphoma C1ac. Immunomodulatory effects of resveratrol T-cell lymphoma C1ad. Modulation of gene expression by resveratrol Myeloid leukemia C2. In vivo animal studies of resveratrol Breast cancer C2a. Metabolism, pharmacokinetics, tissue distribution and Colon cancer clearance of resveratrol Pancreatic cancer C2b. Chemopreventive effects of resveratrol in animals Gastric cancer C2c. Antitumor effects of resveratrol in animals Prostate cancer D. Clinical studies with resveratrol Melanoma Lung cancer Conclusion Liver cancer Thyroid and head and neck cancers References Ovarian and endometrial tumors C1b. Resveratrol induces apoptosis Introduction Fas/CD95 pathway Mitochondrial pathway The history of resveratrol can be traced back thousands of Rb-E2F/DP pathway years. Perhaps the first known use of grape extracts for p53 activation pathway human health can be dated over 2000 years ago, to Ceramide activation pathway "darakchasava", a well-known Indian herbal preparation of Tubulin polymerization pathway which the main ingredient is Vitis vinifera L. This Adenylyl-cyclase pathway "Ayurvedic" medicine is prescribed as a cardiotonic and also C1c. Suppression of NF-Î B activation by resveratrol given for other disorders (1). The use of dried grapes (also C1d. Suppression of AP-1 by resveratrol called manakka) as a cardiotonic is well documented. High- C1e. Suppression of Egr-1 by resveratrol performance liquid choromatography (HPLC) analysis of C1f. Suppression of mitogen-activated protein kinases by darakchasava revealed polyphenols such as resveratrol and resveratrol pterostilbene. This age-old formulation became interesting C1g. Suppression of protein kinases by resveratrol in the light of recently acquired knowledge on resveratrol. 2784 Aggarwal et al: Resveratrol Inhibits Tumorigenesis Figure 1. Sources of resveratrol from different plants. Resveratrol (3,5,4’-trihydroxystilbene) is a naturally synthase gene from grapevine, transferred it into tobacco, occurring phytoalexin produced by a wide variety of plants, and found that regenerated tobacco plants containing this such as grapes (Vitis vinifera), peanuts (Arachis hypogea), gene are more resistant to infection by Botrytis cinerea (2). and mulberries in response to stress, injury, ultraviolet (UV) Resveratrol was first identified in 1940 as a constituent of irradiation, and fungal (e.g., Botrytis cinerea) infection. the roots of white hellebore
Load more

Recommended publications
  • Stilbenes: Chemistry and Pharmacological Properties
    1 Journal of Applied Pharmaceutical Research 2015, 3(4): 01-07 JOURNAL OF APPLIED PHARMACEUTICAL RESEARCH ISSN No. 2348 – 0335 www.japtronline.com STILBENES: CHEMISTRY AND PHARMACOLOGICAL PROPERTIES Chetana Roat*, Meenu Saraf Department of Microbiology & Biotechnology, University School of Sciences, Gujarat University, Ahmedabad, Gujarat 380009, India Article Information ABSTRACT: Medicinal plants are the most important source of life saving drugs for the Received: 21st September 2015 majority of the Worlds’ population. The compounds which synthesized in the plant from the Revised: 15th October 2015 secondary metabolisms are called secondary metabolites; exhibit a wide array of biological and Accepted: 29th October 2015 pharmacological properties. Stilbenes a small class of polyphenols, have recently gained the focus of a number of studies in medicine, chemistry as well as have emerged as promising Keywords molecules that potentially affect human health. Stilbenes are relatively simple compounds Stilbene; Chemistry; synthesized by plants and deriving from the phenyalanine/ polymalonate route, the last and key Structures; Biosynthesis pathway; enzyme of this pathway being stilbene synthase. Here, we review the biological significance of Pharmacological properties stilbenes in plants together with their biosynthesis pathway, its chemistry and its pharmacological significances. INTRODUCTION quantities are present in white and rosé wines, i.e. about a tenth Plants are source of several drugs of natural origin and hence of those of red wines. Among these phenolic compounds, are termed as the medicinal plants. These drugs are various trans-resveratrol, belonging to the stilbene family, is a major types of secondary metabolites produced by plants; several of active ingredient which can prevent or slow the progression of them are very important drugs.
    [Show full text]
  • Desoxyrhapontigenin Inhibits RANKL‑Induced Osteoclast Formation and Prevents Inflammation‑Mediated Bone Loss
    INTERNATIONAL JOURNAL OF MOleCular meDICine 42: 569-578, 2018 Desoxyrhapontigenin inhibits RANKL‑induced osteoclast formation and prevents inflammation‑mediated bone loss PHUONG THAO TRAN1, DONG-HWA PARK2, OKHWA KIM1, SEUNG-HAE KWON3, BYUNG-SUN MIN2 and JEONG-HYUNG LEE1 1Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-Do 24341; 2College of Pharmacy, Catholic University of Daegu, Hayang, Gyeongbuk 38430; 3Division of Bio-Imaging, Korea Basic Science Institute Chuncheon Center, Chuncheon, Gangwon-Do 24341, Republic of Korea Received November 6, 2017; Accepted March 15, 2018 DOI: 10.3892/ijmm.2018.3627 Abstract. Desoxyrhapontigenin (DRG), a stilbene compound mouse model. At the molecular level, DRG inhibited the from Rheum undulatum, has been found to exhibit various RANKL-induced activation of extracellular signal-regulated pharmacological activities, however, its impact on osteoclast kinase, the expression of c-Fos, and the induction of NFATc1, formation has not been investigated. The present study inves- a crucial transcription factor for osteoclast formation. DRG tigated the effect of DRG on receptor activator of nuclear decreased the expression levels of osteoclast marker genes, factor-κB ligand (RANKL)-induced osteoclast differen- including matrix metalloproteinase-9, tartrate-resistant acid tiation in mouse bone marrow macrophages (BMMs) and phosphatase and cathepsin K. In conclusion, these findings inflammation‑induced bone loss in vivo. BMMs or RAW264.7 suggested that DRG inhibited the differentiation of BMMs cells were treated with DRG, followed by an evaluation of into mature osteoclasts by suppressing the RANKL-induced cell viability, RANKL-induced osteoclast differentiation, activator protein-1 and NFATc1 signaling pathways, and actin-ring formation and resorption pits activity.
    [Show full text]
  • Spruce Bark Extract As a Sun Protection Agent in Sunscreens
    Mengmeng Sui Spruce bark extract as a Sun protection agent in sunscreens School of Chemical Engineering Master’s Program in Chemical, Biochemical and Materials Engineering Major in Chemical Engineering Master’s thesis for the degree of Master of Science in Technology Submitted for inspection, Espoo 21.07.2018 Thesis supervisor: Prof. Tapani Vuorinen Thesis advisors: M.Sc. (Tech.) Jinze Dou Ph.D. Kavindra Kesari AALTO UNIVERSITY SCHOLLO OF CHEMICAL ENGINEERING ABSTRACT Author: Mengmeng Sui Title: Spruce bark extract as a sun protection agent in sunscreens Date: 21.07. 2018 Language: English Number of pages: 48+7 Master’s programme in Chemical, Biochemical and Materials Engineering Major: Chemical and Process Engineering Supervisor: Prof: Tapani Vuorinen Advisors: M.Sc. (Tech.) Jinze Dou, Ph.D. Kavindra Kesari This study aimed to clarify the feasibility of utilizing spruce inner bark extract as a sun protection agent in sunscreens. Ultrasound-assisted extraction with 60 v-% ethanol was applied to isolate the extract in 25-30 % yield, that was almost independent of the temperature (45-75oC) and time (5-60 min) of the treatment. However, the yield of stilbene glucosides, measured by UV absorption spectroscopy, was highest after ca. 20 min extraction. Nuclear magnetic resonance spectroscopy of the extract showed that it consisted mainly of three stilbene glucosides, astringin, isorhapontin and polydatin (piceid). The maximum overall yield of the stilbene glucosides was > 20 %. Extraction with water gave a much lower yield of the stilbene glucosides. Sunscreens composed of a mixture of vegetable oils, surfactants (fatty acids), glycerin, water and the bark extract were prepared with the low-energy emulsification method.
    [Show full text]
  • Fflc^Cj^^Lljp^ O Sources and Chemistry of Resveratrol
    fflc^cj^^lljp^ O Sources and Chemistry of Resveratrol Navindra P. Seeram University of California, Los Angeles Vishal V. Kulkarni and Subhash Padhye University of Pune, India CONTENTS Introduction 17 Sources of Resveratrol 18 Structure of Resveratrol 22 Chemical Analyses of Resveratrol 23 Synthesis of Resveratrol 24 Theoretical and SAR Studies of Resveratrol 25 Conclusion 26 References 26 INTRODUCTION Stilbenoids are phenol-based plant metabolites widely represented in nature and implicated with human health benefits against problems such as cancer, inflammation, neurodegenerative disease, and heart disease. Among stilbenes, the phytoalexin resveratrol (3,4',5-trihydroxystilbene; Figure 2.1) has attracted immense attention from biologists and chemists due to its numerous biological properties. Resveratrol is a pivotal molecule in plant biology and plays an important role as the parent molecule of oligo­ mers known as the viniferins [1]. It is also found in nature as closely related analogs, derivatives, and conjugates (Table 2.1) [1-80]. In addition, the inherent structural simplicity of the resveratrol molecule allows for the rational design of new chemotherapeutic agents, and hence a number of its synthetic adducts, analogs, derivatives, and conjugates have been reported (Table 2.1) [1-80]. 17 18 Resveratrol in Health and Disease Trans-resveratrol (frans-3,4',5-trihydroxystilbene) C/s-resveratrol (c/s-3,4',5-trihydroxystilbene) FIGURE 2.1 Chemical structures of trans- and r/.v-resveratrol (3.4'. .5-trihydrox- vstilbene). Numerous efforts have been directed to studies of structure-activity relationships (SARs) of resveratrol and its analogs with the goal of increasing and enhancing their //; V/IY; biological potency and bioavailability.
    [Show full text]
  • Optimization of Bioactive Polyphenols Extraction from Picea Mariana Bark
    molecules Article Optimization of Bioactive Polyphenols Extraction from Picea Mariana Bark Nellie Francezon 1,2, Naamwin-So-Bâwfu Romaric Meda 1,2 and Tatjana Stevanovic 1,2,* 1 Renewable Materials Research Centre, Department of Wood and Forest Sciences, Université Laval, Québec, QC G1V 0A6, Canada; [email protected] (N.F.); [email protected] (N.-S.-B.R.M.) 2 Institute of Nutrition and Functional Food (INAF), Université Laval, Quebec, QC G1V 0A6, Canada * Correspondence: [email protected]; Tel.: +1-418-656-2131 Received: 30 October 2017; Accepted: 30 November 2017; Published: 1 December 2017 Abstract: Reported for its antioxidant, anti-inflammatory and non-toxicity properties, the hot water extract of Picea mariana bark was demonstrated to contain highly valuable bioactive polyphenols. In order to improve the recovery of these molecules, an optimization of the extraction was performed using water. Several extraction parameters were tested and extracts obtained analyzed both in terms of relative amounts of different phytochemical families and of individual molecules concentrations. As a result, low temperature (80 ◦C) and low ratio of bark/water (50 mg/mL) were determined to be the best parameters for an efficient polyphenol extraction and that especially for low molecular mass polyphenols. These were identified as stilbene monomers and derivatives, mainly stilbene glucoside isorhapontin (up to 12.0% of the dry extract), astringin (up to 4.6%), resveratrol (up to 0.3%), isorhapontigenin (up to 3.7%) and resveratrol glucoside piceid (up to 3.1%) which is here reported for the first time for Picea mariana. New stilbene derivatives, piceasides O and P were also characterized herein as new isorhapontin dimers.
    [Show full text]
  • List of Compounds 2018 年12 月
    List of Compounds 2018 年12 月 長良サイエンス株式会社 Nagara Science Co., Ltd. 〒501-1121 岐阜市古市場 840 840 Furuichiba, Gifu 501-1121, JAPAN Phone : +81-58-234-4257、Fax : +81-58-234-4724 E-mail : [email protected] 、http : //www.nsgifu.jp Storage Product Name・Purity・Molecular Formula＝Molecular Weight・〔 CAS Quantity Source Code No. C o n di t i o n s Registry Number 〕 ・Price ( JPY ) NH020102 2－10 ℃ (-)-Epicatechin [ (-)-EC ] ≧99% (HPLC) 10mg 8,000 NH020103 C15H14O6 = 290.27 〔490-46-0〕 100mg 44,000 NH020202 2－10 ℃ (-)-Epigallocatechin [ (-)-EGC ] ≧99% (HPLC) 10mg 12,000 NH020203 C15H14O7 = 306.27 〔970-74-1〕 100mg 66,000 NH020302 2－10 ℃ (-)-Epicatechin gallate [ (-)-ECg ] ≧99% (HPLC) 10mg 12,000 NH020303 C22H18O10 = 442.37 〔1257-08-5〕 100mg 52,000 NH020403 2－10 ℃ (-)-Epigallocatechin gallate [ (-)-EGCg ] ≧98% (HPLC) 100mg 12,000 〔 〕 C22H18O11 = 458.37 989-51-5 NH020602 2－10 ℃ (-)-Epigallocatechin gallate [ (-)-EGCg ] ≧99% (HPLC) 20mg 12,000 NH020603 C22H18O11 = 458.37 〔989-51-5〕 100mg 30,000 NH020502 2－10 ℃ (+)-Catechin hydrate [ (+)-C ] ≧99% (HPLC) 10mg 5,000 NH020503 C15H14O6 ･H2O = 308.28 〔88191-48-4〕 100mg 32,000 NH021102 2－10 ℃ (-)-Catechin [ (-)-C ] ≧98% (HPLC) 10mg 23,000 C15H14O6 = 290.27 〔18829-70-4〕 NH021202 2－10 ℃ (-)-Gallocatechin [ (-)-GC ] ≧98% (HPLC) 10mg 34,000 〔 〕 C15H14O7 = 306.27 3371-27-5 NH021302 － ℃ ≧ 10mg 34,000 2 10 (-)-Catechin gallate [ (-)-Cg ] 98% (HPLC) C22H18O10 = 442.37 〔130405-40-2〕 NH021402 2－10 ℃ (-)-Gallocatechin gallate [ (-)-GCg ] ≧98% (HPLC) 10mg 23,000 C22H18O11 = 458.37 〔4233-96-9〕 NH021502 2－10 ℃ (+)-Epicatechin [ (+)-EC
    [Show full text]
  • Applications of Mass Spectrometry in Natural Product Drug Discovery for Malaria: Targeting Plasmodium Falciparum Thioredoxin Reductase
    Applications of mass spectrometry in natural product drug discovery for malaria: Targeting Plasmodium falciparum thioredoxin reductase by Ranjith K. Munigunti A dissertation submitted to the Graduate Faculty of Auburn University in partial fulfillment of the requirements for the Degree of Doctor of Philosophy Auburn, Alabama May 5, 2013 Keywords: Chromatography, mass spectrometry, malaria, Plasmodium falciparum, thioredoxin reductase, thioredoxin Copyright 2013 by Ranjith K. Munigunti Approved by Angela I. Calderón, Chair, Assistant Professor of Pharmacal Sciences C. Randall Clark, Professor of Pharmacal Sciences Jack DeRuiter, Professor of Pharmacal Sciences Forrest Smith, Associate Professor of Pharmacal Sciences Orlando Acevedo, Associate Professor of Chemistry and Biochemistry Abstract Malaria is considered to be the dominant cause of death in low income countries especially in Africa. Malaria caused by Plasmodium falciparum is a most lethal form of the disease because of its rapid spread and the development of drug resistance. The main problem in the treatment of malaria is the emergence of drug resistant malaria parasites. Over the years/decades, natural products have been used for the treatment or prevention of number of diseases. They can serve as compounds of interest both in their natural form and as templates for synthetic modification. Nature has provided a wide variety of compounds that inspired the development of potential therapeutics such as quinine, artemisinin and lapachol as antimalarial agents. As the resistance to known antimalarials is increasing, there is a need to expand the antimalarial drug discovery efforts for new classes of molecules to combat malaria. This research work focuses on the applications of ultrafiltration, mass spectrometry and molecular modeling based approaches to identify inhibitors of Plasmodium falciparum thioredoxin reductase (PfTrxR), our main target and Plasmodium falciparum glutathione reductase (PfGR) as an alternative target for malaria drug discovery.
    [Show full text]
  • Oxyresveratrol의 기원, 생합성, 생물학적 활성 및 약물동력학
    KOREAN J. FOOD SCI. TECHNOL. Vol. 47, No. 5, pp. 545~555 (2015) http://dx.doi.org/10.9721/KJFST.2015.47.5.545 총설 ©The Korean Society of Food Science and Technology Oxyresveratrol의 기원, 생합성, 생물학적 활성 및 약물동력학 임영희·김기현 1·김정근 1,* 고려대학교 보건과학대학 바이오시스템의과학부, 1한국산업기술대학교 생명화학공학과 Source, Biosynthesis, Biological Activities and Pharmacokinetics of Oxyresveratrol 1 1, Young-Hee Lim, Ki-Hyun Kim , and Jeong-Keun Kim * School of Biosystem and Biomedical Science, Korea University 1Department of Chemical Engineering and Biotechnology, Korea Polytechnic University Abstract Oxyresveratrol (trans-2,3',4,5'-tetrahydroxystilbene) has been receiving increasing attention because of its astonishing biological activities, including antihyperlipidemic, neuroprotection, antidiabetic, anticancer, antiinflammation, immunomodulation, antiaging, and antioxidant activities. Oxyresveratrol is a stilbenoid, a type of natural phenol and a phytoalexin produced in the roots, stems, leaves, and fruits of several plants. It was first isolated from the heartwood of Artocarpus lakoocha, and has also been found in various plants, including Smilax china, Morus alba, Varatrum nigrum, Scirpus maritinus, and Maclura pomifera. Oxyresveratrol, an aglycone of mulberroside A, has been produced by microbial biotransformation or enzymatic hydrolysis of a glycosylated stilbene mulberroside A, which is one of the major compounds of the roots of M. alba. Oxyresveratrol shows less cytotoxicity, better antioxidant activity and polarity, and higher cell permeability and bioavailability than resveratrol (trans-3,5,4'-trihydroxystilbene), a well-known antioxidant, suggesting that oxyresveratrol might be a potential candidate for use in health functional food and medicine. This review focuses on the plant sources, chemical characteristics, analysis, biosynthesis, and biological activities of oxyresveratrol as well as describes the perspectives on further exploration of oxyresveratrol.
    [Show full text]
  • Literature Review Zero Alcohol Red Wine
    A 1876 LI A A U R S T T S R U A L A I A FLAVOURS, FRAGRANCES AND INGREDIENTS 6 1 7 8 7 8 1 6 A I B A L U A S R T B Essential Oils, Botanical Extracts, Cold Pressed Oils, BOTANICAL Infused Oils, Powders, Flours, Fermentations INNOVATIONS LITERATURE REVIEW HEALTH BENEFITS RED WINE ZERO ALCOHOL RED WINE RED WINE EXTRACT POWDER www.botanicalinnovations.com.au EXECUTIVE SUMMARY The term FRENCH PARADOX is used to describe the relatively low incidence of cardiovascular disease in the French population despite the high consumption of red wine. Over the past 27 years numerous clinical studies have found a linkages with the ANTIOXIDANTS in particular, the POLYPHENOLS, RESVERATROL, CATECHINS, QUERCERTIN and ANTHOCYANDINS in red wine and reduced incidences of cardiovascular disease. However, the alcohol in wine limits the benefits of wine. Studies have shown that zero alcohol red wine and red wine extract which contain the same ANTIOXIDANTS including POLYPHENOLS, RESVERATROL, CATECHINS, QUERCERTIN and ANTHOCYANDINS has the same is not more positive health benefits. The following literature review details some of the most recent positive health benefits derived from the ANTIOXIDANTS found in red wine POLYPHENOLS: RESVERATROL, CATECHINS, QUERCERTIN and ANTHOCYANDINS. The positive polyphenolic antioxidant effects of the polyphenols in red wine include: • Cardio Vascular Health Benefits • Increase antioxidants in the cardiovascular system • Assisting blood glucose control • Skin health • Bone Health • Memory • Liking blood and brain health • Benefits
    [Show full text]
  • Molecular Cloning and Functional Characterization of an O-Methyltransferase Catalyzing 4 -O-Methylation of Resveratrol in Acorus
    Journal of Bioscience and Bioengineering VOL. 127 No. 5, 539e543, 2019 www.elsevier.com/locate/jbiosc Molecular cloning and functional characterization of an O-methyltransferase catalyzing 40-O-methylation of resveratrol in Acorus calamus Takao Koeduka,1,* Miki Hatada,1 Hideyuki Suzuki,2 Shiro Suzuki,3 and Kenji Matsui1 Graduate School of Sciences and Technology for Innovation (Agriculture), Department of Biological Chemistry, Yamaguchi University, Yamaguchi 753-8515, Japan,1 Department of Applied Genomics, Kazusa DNA Research Institute, Chiba 292-0818, Japan,2 and Research Institute for Sustainable Humanosphere, Kyoto University, Kyoto 611-0011, Japan3 Received 17 July 2018; accepted 13 October 2018 Available online 22 November 2018 Resveratrol and its methyl ethers, which belong to a class of natural polyphenol stilbenes, play important roles as biologically active compounds in plant defense as well as in human health. Although the biosynthetic pathway of resveratrol has been fully elucidated, the characterization of resveratrol-specific O-methyltransferases remains elusive. In this study, we used RNA-seq analysis to identify a putative aromatic O-methyltransferase gene, AcOMT1,inAcorus calamus. Recombinant AcOMT1 expressed in Escherichia coli showed high 40-O-methylation activity toward resveratrol and its derivative, isorhapontigenin. We purified a reaction product enzymatically formed from resveratrol by AcOMT1 and confirmed it as 40-O-methylresveratrol (deoxyrhapontigenin). Resveratrol and isorhapontigenin were the most preferred substrates with apparent Km values of 1.8 mM and 4.2 mM, respectively. Recombinant AcOMT1 exhibited reduced activity toward other resveratrol derivatives, piceatannol, oxyresveratrol, and pinostilbene. In contrast, re- combinant AcOMT1 exhibited no activity toward pterostilbene or pinosylvin. These results indicate that AcOMT1 showed high 40-O-methylation activity toward stilbenes with non-methylated phloroglucinol rings.
    [Show full text]
  • Anti-Tumor Properties of Methoxylated Analogues of Resveratrol in Malignant MCF-7 but Not in Non-Tumorigenic MCF-10A Mammary Epithelial Cell Lines T ⁎ Annick D
    Toxicology 422 (2019) 35–43 Contents lists available at ScienceDirect Toxicology journal homepage: www.elsevier.com/locate/toxicol Anti-tumor properties of methoxylated analogues of resveratrol in malignant MCF-7 but not in non-tumorigenic MCF-10A mammary epithelial cell lines T ⁎ Annick D. van den Brand , Judith Villevoye, Sandra M. Nijmeijer, Martin van den Berg, Majorie B.M. van Duursen Institute for Risk Assessment Sciences, Toxicology Department, Utrecht University, Yalelaan 104, 3584 CM, Utrecht, the Netherlands ARTICLE INFO ABSTRACT Keywords: Resveratrol is a plant-derived polyphenol that is known for its anti-inflammatory and anti-tumorigenic prop- Cell cycle erties in in vitro and in vivo models. Recent studies show that some resveratrol analogues might be more potent Gene expression anti-tumor agents, which may partly be attributed to their ability to activate the aryl hydrocarbon receptor Breast cancer (AHR). Here, the anti-tumorigenic properties of resveratrol and structural analogues oxyresveratrol, pinos- Resveratrol tilbene, pterostilbene and tetramethoxystilbene (TMS) were studied in vitro, using in the malignant human MCF- 7 breast cancer cell line and non-tumorigenic breast epithelial cell line MCF-10A. Cell viability and migration assays showed that methoxylated analogues of resveratrol are more potent anti- tumorigenic compounds than resveratrol and its hydroxylated analogue oxyresveratrol, with 2,3’,4,5’-tetra- methoxy-trans-stilbene (TMS) being the most potent compound. TMS decreased MCF-7 tumor cell viability with 50% at 3.6 μM and inhibited migration with 37.5 ± 14.8% at 3 μM. In addition, TMS activated the AHR more potently (EC50 in a reporter gene assay 2.0 μM) and induced AHR-mediated induction of cytochrome P450 1A1 (CYP1A1) activity (EC50 value of 0.7 μM) more than resveratrol and the other analogues tested.
    [Show full text]
  • Resveratrol 98% Natural (Japanese Knotweed)
    Resveratrol 98% Natural (Japanese Knotweed) Cambridge Commodities Chemwatch Hazard Alert Code: 3 Part Number: P33926 Issue Date: 04/03/2019 Version No: 1.1.23.11 Print Date: 29/09/2021 Safety data sheet according to REACH Regulation (EC) No 1907/2006, as amended by UK REACH Regulations SI 2019/758 S.REACH.GB.EN SECTION 1 Identification of the substance / mixture and of the company / undertaking 1.1. Product Identifier Product name Resveratrol 98% Natural (Japanese Knotweed) Chemical Name resveratrol Synonyms Not Available Chemical formula Not Applicable Other means of P33926 identification 1.2. Relevant identified uses of the substance or mixture and uses advised against The pharmacological activities and mechanisms of action of natural phenylpropanoid glycosides (PPGs) extracted from a variety of plants such as antitumor, antivirus, anti-inflammation, antibacteria, antiartherosclerosis, anti-platelet-aggregation, antihypertension, antifatigue, analgesia, hepatoprotection, immunosuppression, protection of sex and learning behavior, protection of neurodegeneration, reverse transformation of tumor cells, inhibition of telomerase and shortening telomere length in tumor cells, effects on enzymes and cytokines, antioxidation, free radical scavenging and fast repair of oxidative damaged DNA, have been reported in the literature. Phenylpropanoids (PPs) belong to the largest group of secondary metabolites produced by plants, mainly, in response to biotic or abiotic stresses such as infections, wounding, UV irradiation, exposure to ozone, pollutants, and other hostile environmental conditions. It is thought that the molecular basis for the protective action of phenylpropanoids in plants is their antioxidant and free radical scavenging properties. These numerous phenolic compounds are major biologically active components of human diet, spices, aromas, wines, beer, essential oils,propolis, and traditional medicine.
    [Show full text]