DOCSLIB.ORG

E. R. E. E.O.E. the Present Invention Provides Novel Compounds with Hypot

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

US0093.76369B2 (12) United States Patent (10) Patent No.: US 9,376,369 B2 Chatterjee (45) Date of Patent: Jun. 28, 2016 (54) ANTI-CHOLESTEROLEMIC COMPOUNDS OTHER PUBLICATIONS AND METHODS OF USE Muruganandam et al. Indian Journal of Experimental Biology, vol. 40, Oct. 2002, pp. 1151-1160.* (71) Applicant: Subroto Chatterjee, Columbia, MD Wang et al..Journal of Ethnopharmacology 96 (2005) 483-487, pub (US) lished online Nov. 11, 2004.* Conner et al. Nutrition 12:274-277, 1996.* (72) Inventor: Subroto Chatterjee, Columbia, MD Definition of Inflammation by Medical dictionary, http://medical (US) dictionary.thefreedictionary.com/Inflammation, internet article downloaded Sep. 22, 2015.* - r Chae, Hypertension, 2001; 38:399-403.* (*) Notice: Subject to any disclaimer the term of this Abe I et al. "Potent and selective inhibition of squalene epoxidase by past list: G adjusted under 35 synthetic galloyl esters.” Biochem Biophys Res Commun. Apr. 2, M YW- y U days. 2000:270(1): 137-40. Alzheimer's Disease—downloaded Jun. 2011 from PubMed Health. (21)21) AppAppl. No.: 13/946,5589 American Heart Association, Cholesterol Abnormalities & Dis ease—downloaded Jun. 2011. (22) Filed: Jul.19, 2013 Baker, State University of New York at Buffalo Reporter, vol. 28, No. 35: Jul 24, 1997. O O Crespy Vetal. "A review of the health effects of green tea catechins (65) Prior Publication Data in in vivo animal models.” JNutr. Dec. 2004;134(12 Suppl):3431S US 2014/0031304 A1 Jan. 30, 2014 344OS. s Definition of food—dlownloaded from biology-online.org <http:// biology-online.org>, Jun. 2011. O O Merck Manuals Online: Stroke—downloaded Jun. 2011. Related U.S. Application Data Murase Tetal. “Gallates inhibit cytokine-induced nuclear transloca (63) Continuation of application No. 12488,965, filed on EEEEEE Jun. 22, 2009, now Pat. No. 8,492.351, which is a 1999; 19(6): 1412-20 ve. continuation of application No. PCT/US2007/088780, Muruganandam AV et al. “Effect of poly herbal formulation, EuMil, filed on Dec. 24, 2007. on chronic stress-induced homeostatic perturbations in rats.” Indian J Exp Biol. Oct. 2002:40(10): 1151-60. Abstract Only. (60) Provisional appli cation No. 60/876,761, filed on Dec. Okabe Set al. “New TNF-alpha releasing inhibitors, geraniin and 22, 2006, provisional application No. 60/876,599, corilagin, in leaves of Acer nikoense, Megusurino-ki.” Biol Pharm filed on Dec. 22, 2006, provisional application No. Bull. Oct. 2001:24(10): 1145-8. 60/877,753, filed on Dec. 29, 2006, provisional Okuda et al. In Phenolic Compounds in Food and Their Effects on application No. 60/877,740, filed on Dec. 29, 2006. Health II; ACS Symposium Series; American Chemical Society: Washington, DC, 1992. (51) Int. Cl. Tongia et al. Indian Journal of Indigenous Medicines, Oct. 1995; A2.3L I/30 (2006.01) 17(2): 13-24, abstract only. A6 IK3I/235 (2006.01) Kim et al. Influence of amla (Emblica officinalis Gaertn.) on A6 IK3I/7024 (2006.01) hypercholesterolemia and lipid peroxidation in cholesterol-fed rats. J A6 IK 45/06 (2006.01) Nutr Sci Vitaminol (Tokyo). Dec. 2005:51(6):413-8. CD7C 69/84 2OO 6. O1 Mathur et al. Hypolipidaemic effect of fruit juice of Emblica C7H 3/08 3:08: officinalis in cholesterol-fed rabbits. J Ethnopharmacol. Feb. 1996:50(2):61-8. (52) U.S. Cl. Thakur et al. The Ayurvedic medicines Haritaki, Amala and Bahira CPC ............... C07C 69/84 (2013.01); A23L I/3002 reduce cholesterol-induced atherosclerosis in rabbits. Int J Cardiol. (2013.01); A61 K3I/235 (2013.01); A61 K Nov. 1988:21(2):167-75. 31/7024 (2013.01); A61K 45/06 (2013.01); Zhang et al. Antiproliferative activity of the main constituents from C07H 13/08 (2013.01); A23 V 2002/00 Phyllanthus emblica. Biol Pharm Bull. Feb. 2004:27(2):251-5. (2013.01) k . (58) Field of Classification Search cited by examiner Nes lication file f 1 hhi Primary Examiner — Layla Berry ee application file for complete search history. (74) Attorney, Agent, or Firm — Mintz Levin Cohn Ferris (56) References Cited y and Popeo, P.C.; Peter F. Corless, Esq.; Daniel W. U.S. PATENT DOCUMENTS (57) ABSTRACT 4. E.ww. R. E. E.O.E. Thecholesteremic present invention activity providesfrom crude novel Embilica compounds officinialis with hypot (EO) FOREIGN PATENT DOCUMENTS R R methods of use. The invention also provides UaC1CalS. WO WO-2004/058213 A1 T 2004 WO WO 20060225O2 A1 * 3, 2006 ........... A61K 31,216 13 Claims, 11 Drawing Sheets U.S. Patent US 9,376,369 B2 HOOH OOH.HOOHOHOOH OHOOHOOOH OOH HO HO HOHOHOHOOH OOOSLOÀ? OHOHOOH HOOHHO HOOoHoºsºººo U.S. Patent Jun. 28, 2016 Sheet 3 of 11 US 9,376,369 B2 MONTHS FG. 2 MONTHS FIG. 3 U.S. Patent Jun. 28, 2016 Sheet 4 of 11 US 9,376,369 B2 200 10 O MONTHS FG. 4 U.S. Patent Jun. 28, 2016 Sheet 5 of 11 US 9,376,369 B2 22 S 22222222 S 2 S 22 SS 22. S D 222222222222222 S 2 C C C C c O C N r- y pifu 2 SS 2 S 22 S Z2 S ZZZZZZZZZZZZZZZ S 222222222222 N C C 3. w v pfu U.S. Patent Jun. 28, 2016 Sheet 6 of 11 US 9,376,369 B2 Cholest, 100 NChol, oleate N Ø FIG 6 U.S. Patent US 9,376,369 B2 SOALL Cd eSeld eqo 9, U.S. Patent Jun. 28, 2016 Sheet 8 of 11 US 9,376,369 B2 y c c CN co O cN r g 3 O O C O C O O C N. O w r N w s s (%) uoquoieselolo U.S. Patent Jun. 28, 2016 Sheet 9 of 11 US 9,376,369 B2 140 120 100 80 60 40 20 O Control LOW 2 3 4 4-1 5 6 7 8 7+8 Compounds FG. 9 21030 O O low 1 2 3 4 4+1 5 6 7 8 7-8 Compounds F.G. 10 U.S. Patent Jun. 28, 2016 Sheet 10 of 11 US 9,376,369 B2 2OO 150 1OO 5 O O Control Low 1 2 3 4 4-1 5 6 7 8 7-8 Compounds F.G. 11 U.S. Patent Jun. 28, 2016 Sheet 11 of 11 US 9,376,369 B2 SOAuu e Seleco. 9 US 9,376,369 B2 1. 2 ANT-CHOLESTEROLEMC COMPOUNDS opment of competitive inhibitors for 3-hydroxy-3-methylglu AND METHODS OF USE taryl coenzyme A reductase, a major regulatory enzyme of cholesterol biosynthesis. Many attempts to use for this pur RELATED APPLICATIONS pose oxygenated Sterols, which via binding oxysterol recep tors were expected to decrease activity of HMG-CoA reduc This application is a continuation of U.S. application Ser. tase, did not bring practical results. A series of fungal No. 12/488.965, filed Jun. 22, 2009 (now U.S. Pat. No. 8,492, metabolites with very high affinities for HMG-CoA reductase 351), which is a continuation of International Application No. were found to be highly efficient inhibitors of cholesterol PCT/US2007/088780 (WO 2008/080162) filed Dec. 24, biosynthesis. These compounds and Some synthetic analogs 2007, which claims the benefit of U.S. Provisional Applica 10 are commonly known as statins, are available commercially, tion 60/876,761 filed Dec. 22, 2006, U.S. Provisional Appli and are widely used. cation 60/877,753 filed Dec. 29, 2006, U.S. Provisional Although being relatively safe and efficient in treatment Application 60/876,599 filed Dec. 22, 2006 and U.S. Provi and prevention of coronary heart disease, statins have certain sional Application 60/877,740 filed Dec. 29, 2006. The entire 15 limitations in their use because of possible deleterious side contents of the aforementioned applications are hereby incor effects, such as muscle weakness, and renal failure. Statin porated herein by reference. therapy is contra-indicated in pregnant women and patients GOVERNMENT SUPPORT with liver disorders. Additionally, there is a significant patient population in whom statins are not effective, and so the need This invention was made with support from the United for an agent that will lower cholesterol extends beyond the States Government under grant DK-31771 and DK-31722. number of patients currently taking statins to lower their The US Government has certain rights in this invention. cholesterol levels. Taking additionally into account the rela tively high costs of statin therapy, which varies from $20,000 FIELD OF THE INVENTION to $40,000 per quality-adjusted life-year saved John A. 25 Farmer, Economic Implications of Lipid-Lowering Trials: The present invention provides novel compounds with Current Considerations in Selecting a Statin, Am J Cardiol hypocholesteremic activity from Embilica officinalis (EO) 1998; 82:26 M-31M, and the desirability of long-term per extracts and methods of use. The invention provides nutra manent treatment Terry A. Jacobson, Clinical Context: Cur ceuticals. The invention relates to the determination of the rent Concepts of Coronary Heart Disease Management, Am J. biological activity and mechanism of action by which the 30 Med. 2001; 110 (6A):3S-11S, it is evident that new agents purified compounds lower cholesterol levels. are needed with similar targeting as the statins but with higher potency, safety, and availability and that will provide signifi BACKGROUND OF THE INVENTION cant cost savings. Accordingly, the instant invention provides novel com According to the American Heart Association, an esti 35 pounds with anticholesterolemic activity, and methods of use. mated 100,870,000 American adults have total cholesterol levels in the borderline-high risk range of 200 mg/dl to 239 SUMMARY mg/dl., and there are 40,600,000 American adults living with high-risk cholesterol levels of 240 mg/dl or more.
Recommended publications
  • Structure Activity Relationship of Phenolic Acid Inhibitors of Α-Synuclein fibril Formation and Toxicity

    Structure Activity Relationship of Phenolic Acid Inhibitors of Α-Synuclein fibril Formation and Toxicity

    ORIGINAL RESEARCH ARTICLE published: 05 August 2014 AGING NEUROSCIENCE doi: 10.3389/fnagi.2014.00197 Structure activity relationship of phenolic acid inhibitors of α-synuclein fibril formation and toxicity Mustafa T. Ardah 1, Katerina E. Paleologou 2, Guohua Lv 3, Salema B. Abul Khair 1, Abdulla S. Kazim 1, Saeed T. Minhas 4, Taleb H. Al-Tel 5, Abdulmonem A. Al-Hayani 6, Mohammed E. Haque 1, David Eliezer 3 and Omar M. A. El-Agnaf 1,7* 1 Department of Biochemistry, College of Medicine and Health Science, United Arab Emirates University, Al Ain, UAE 2 Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece 3 Department of Biochemistry, Weill Cornell Medical College, Cornell University, New York, NY, USA 4 Department of Anatomy, College of Medicine and Health Science, United Arab Emirates University, Al Ain, UAE 5 College of Pharmacy and Sharjah Institute for Medical Research, University of Sharjah, Sharjah, UAE 6 Department of Anatomy, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia 7 Faculty of Medicine, King Abdel Aziz University, Jeddah, Saudi Arabia Edited by: The aggregation of α-synuclein (α-syn) is considered the key pathogenic event in many Edward James Calabrese, University neurological disorders such as Parkinson’s disease (PD), dementia with Lewy bodies and of Massachusetts/Amherst, USA multiple system atrophy, giving rise to a whole category of neurodegenerative diseases Reviewed by: known as synucleinopathies. Although the molecular basis of α-syn toxicity has not been Kenjiro Ono, Kanazawa University Graduate School of Medical precisely elucidated, a great deal of effort has been put into identifying compounds that Science, Japan could inhibit or even reverse the aggregation process.
  • Monocyclic Phenolic Acids; Hydroxy- and Polyhydroxybenzoic Acids: Occurrence and Recent Bioactivity Studies

    Monocyclic Phenolic Acids; Hydroxy- and Polyhydroxybenzoic Acids: Occurrence and Recent Bioactivity Studies

    Molecules 2010, 15, 7985-8005; doi:10.3390/molecules15117985 OPEN ACCESS molecules ISSN 1420-3049 www.mdpi.com/journal/molecules Review Monocyclic Phenolic Acids; Hydroxy- and Polyhydroxybenzoic Acids: Occurrence and Recent Bioactivity Studies Shahriar Khadem * and Robin J. Marles Natural Health Products Directorate, Health Products and Food Branch, Health Canada, 2936 Baseline Road, Ottawa, Ontario K1A 0K9, Canada * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +1-613-954-7526; Fax: +1-613-954-1617. Received: 19 October 2010; in revised form: 3 November 2010 / Accepted: 4 November 2010 / Published: 8 November 2010 Abstract: Among the wide diversity of naturally occurring phenolic acids, at least 30 hydroxy- and polyhydroxybenzoic acids have been reported in the last 10 years to have biological activities. The chemical structures, natural occurrence throughout the plant, algal, bacterial, fungal and animal kingdoms, and recently described bioactivities of these phenolic and polyphenolic acids are reviewed to illustrate their wide distribution, biological and ecological importance, and potential as new leads for the development of pharmaceutical and agricultural products to improve human health and nutrition. Keywords: polyphenols; phenolic acids; hydroxybenzoic acids; natural occurrence; bioactivities 1. Introduction Phenolic compounds exist in most plant tissues as secondary metabolites, i.e. they are not essential for growth, development or reproduction but may play roles as antioxidants and in interactions between the plant and its biological environment. Phenolics are also important components of the human diet due to their potential antioxidant activity [1], their capacity to diminish oxidative stress- induced tissue damage resulted from chronic diseases [2], and their potentially important properties such as anticancer activities [3-5].
  • Purification and Characterization of a Soluble Salicylic Acid-Binding

    Purification and Characterization of a Soluble Salicylic Acid-Binding

    Proc. Natl. Acad. Sci. USA Vol. 90, pp. 9533-9537, October 1993 Biochemistry Purification and characterization of a soluble salicylic acid-binding protein from tobacco (monoclonal antibody/pathogenesis-related proteins/plant defense mechanism/plant signal transduction/systemic acquired resistance) ZHIXIANG CHEN, JOSEPH W. RICIGLIANO, AND DANIEL F. KLESSIG* Waksman Institute, Rutgers, The State University of New Jersey, Piscataway, NJ 08855-0759 Communicated by Charles S. Levings III, July 12, 1993 (received for review May 11, 1993) ABSTRACT Previously, we identified a soluble salicylic SA in the induction of defense responses is provided by the acid (SA)-binding protein (SABP) in tobacco whose properties transgenic tobacco plants which contain and constitutively suggest that it may play a role in transmitting the SA signal express the nahG gene encoding salicylate hydroxylase from during plant defense responses. This SA-binding activity has Pseudomonas putida (21). In these transgenic plants, induc- been purified 250-fold by conventional chromatography and tion of SAR by inoculation with tobacco mosaic virus was was found to copurify with a 280-kDa protein. Monoclonal blocked, presumably due to the destruction of the SA signal antibodies capable of immunoprecipitating the SA-binding by the hydroxylase. activity also immunoprecipitated the 280-kDa protein, indicat- We have been interested in identifying cellular compo- ing that it was responsible for binding SA. These antibodies also nent(s) which directly interact with SA, as a first step to recognized the 280-kDa protein in immunoblots ofthe partially elucidate the mechanism(s) of action of SA in plant signal purified SABP fraction or the crude extract.
  • Hplc∓Dad∓ESI-MS/MS Screening of Bioactive Components

    Hplc∓Dad∓ESI-MS/MS Screening of Bioactive Components

    Food Chemistry 166 (2015) 179–191 Contents lists available at ScienceDirect Food Chemistry journal homepage: www.elsevier.com/locate/foodchem HPLC–DAD–ESI-MS/MS screening of bioactive components from Rhus coriaria L. (Sumac) fruits ⇑ Ibrahim M. Abu-Reidah a,b,c, Mohammed S. Ali-Shtayeh a, , Rana M. Jamous a, David Arráez-Román b,c, ⇑ Antonio Segura-Carretero b,c, a Biodiversity & Environmental Research Center (BERC), Til, Nablus POB 696, Palestine b Department of Analytical Chemistry, Faculty of Sciences, University of Granada, Avda. Fuentenueva, 18071 Granada, Spain c Functional Food Research and Development Centre (CIDAF), PTS Granada, Avda. del Conocimiento, Edificio Bioregión, 18016 Granada, Spain article info abstract Article history: Rhus coriaria L. (sumac) is an important crop widely used in the Mediterranean basin as a food spice, and Received 25 March 2014 also in folk medicine, due to its health-promoting properties. Phytochemicals present in plant foods are in Received in revised form 29 May 2014 part responsible for these consequent health benefits. Nevertheless, detailed information on these Accepted 3 June 2014 bioactive compounds is still scarce. Therefore, the present work was aimed at investigating the Available online 12 June 2014 phytochemical components of sumac fruit epicarp using HPLC–DAD–ESI-MS/MS in two different ionisation modes. The proposed method provided tentative identification of 211 phenolic and other Keywords: phyto-constituents, most of which have not been described so far in R. coriaria fruits. More than 180 Palestinian sumac phytochemicals (tannins, (iso)flavonoids, terpenoids, etc.) are reported herein in sumac fruits for the first Anacardiaceae Hydrolysable tannins time.
  • "Ellagic Acid, an Anticarcinogen in Fruits, Especially in Strawberries: a Review"

    "Ellagic Acid, an Anticarcinogen in Fruits, Especially in Strawberries: a Review"

    FEATURE Ellagic Acid, an Anticarcinogen in Fruits, Especially in Strawberries: A Review John L. Maasl and Gene J. Galletta2 Fruit Laboratory, U.S. Department of Agriculture, Agricultural Research Service, Beltsville, MD 20705 Gary D. Stoner3 Department of Pathology, Medical College of Ohio, Toledo, OH 43699 The various roles of ellagic acid as an an- digestibility of natural forms of ellagic acid, Mode of inhibition ticarcinogenic plant phenol, including its in- and the distribution and organ accumulation The inhibition of cancer by ellagic acid hibitory effects on chemically induced cancer, or excretion in animal systems is in progress appears to occur through the following its effect on the body, occurrence in plants at several institutions. Recent interest in el- mechanisms: and biosynthesis, allelopathic properties, ac- lagic acid in plant systems has been largely a. Inhibition of the metabolic activation tivity in regulation of plant hormones, for- for fruit-juice processing and wine industry of carcinogens. For example, ellagic acid in- mation of metal complexes, function as an applications. However, new studies also hibits the conversion of polycyclic aromatic antioxidant, insect growth and feeding in- suggest that ellagic acid participates in plant hydrocarbons [e.g., benzo (a) pyrene, 7,12- hibitor, and inheritance are reviewed and hormone regulatory systems, allelopathic and dimethylbenz (a) anthracene, and 3-methyl- discussed in relation to current and future autopathic effects, insect deterrent princi- cholanthrene], nitroso compounds (e.g., N- research. ples, and insect growth inhibition, all of which nitrosobenzylmethylamine and N -methyl- N- Ellagic acid (C14H6O8) is a naturally oc- indicate the urgent need for further research nitrosourea), and aflatoxin B1 into forms that curring phenolic constituent of many species to understand the roles of ellagic acid in the induce genetic damage (Dixit et al., 1985; from a diversity of flowering plant families.
  • Molecular Docking Study on Several Benzoic Acid Derivatives Against SARS-Cov-2

    Molecular Docking Study on Several Benzoic Acid Derivatives Against SARS-Cov-2

    molecules Article Molecular Docking Study on Several Benzoic Acid Derivatives against SARS-CoV-2 Amalia Stefaniu *, Lucia Pirvu * , Bujor Albu and Lucia Pintilie National Institute for Chemical-Pharmaceutical Research and Development, 112 Vitan Av., 031299 Bucharest, Romania; [email protected] (B.A.); [email protected] (L.P.) * Correspondence: [email protected] (A.S.); [email protected] (L.P.) Academic Editors: Giovanni Ribaudo and Laura Orian Received: 15 November 2020; Accepted: 1 December 2020; Published: 10 December 2020 Abstract: Several derivatives of benzoic acid and semisynthetic alkyl gallates were investigated by an in silico approach to evaluate their potential antiviral activity against SARS-CoV-2 main protease. Molecular docking studies were used to predict their binding affinity and interactions with amino acids residues from the active binding site of SARS-CoV-2 main protease, compared to boceprevir. Deep structural insights and quantum chemical reactivity analysis according to Koopmans’ theorem, as a result of density functional theory (DFT) computations, are reported. Additionally, drug-likeness assessment in terms of Lipinski’s and Weber’s rules for pharmaceutical candidates, is provided. The outcomes of docking and key molecular descriptors and properties were forward analyzed by the statistical approach of principal component analysis (PCA) to identify the degree of their correlation. The obtained results suggest two promising candidates for future drug development to fight against the coronavirus infection. Keywords: SARS-CoV-2; benzoic acid derivatives; gallic acid; molecular docking; reactivity parameters 1. Introduction Severe acute respiratory syndrome coronavirus 2 is an international health matter. Previously unheard research efforts to discover specific treatments are in progress worldwide.
  • Design and Testing of Safer, More Effective Preservatives For

    Design and Testing of Safer, More Effective Preservatives For

    Research Article pubs.acs.org/journal/ascecg Design and Testing of Safer, More Effective Preservatives for Consumer Products ¶ † ‡ † § † ⊥ Heather L. Buckley,*, , William M. Hart-Cooper, , Jong H. Kim, , David M. Faulkner, § § # ‡ ∇ Luisa W. Cheng, Kathleen L. Chan, Christopher D. Vulpe, William J. Orts, Susan E. Amrose, ¶ and Martin J. Mulvihill ¶ Berkeley Center for Green Chemistry, College of Chemistry, University of California Berkeley, Berkeley, California 94720, United States ‡ Bioproducts Research Unit, Western Regional Research Center, USDA-ARS, 800 Buchanan St., Albany, California 94710, United States § Foodborne Toxin Detection and Prevention Research Unit, Western Regional Research Center, USDA-ARS, 800 Buchanan St., Albany, California 94710, United States ⊥ Berkeley Center for Green Chemistry, Department of Nutritional Sciences and Toxicology, University of California Berkeley, Berkeley, California 94720, United States # Physiological Sciences, Center for Environmental and Human Toxicology, University of Florida, Gainesville, Florida 32611, United States ∇ Civil and Environmental Engineering, University of California Berkeley, Berkeley, California 94720, United States *S Supporting Information ABSTRACT: Preservatives deter microbial growth, providing crucial functions of safety and durability in composite materials, formulated products, and food packaging. Concern for human health and the environmental impact of some preservatives has led to regulatory restrictions and public pressure to remove individual classes of compounds, such as parabens and chromated copper arsenate, from consumer products. Bans do not address the need for safe, effective alternative preservatives, which are critical for both product performance (including lifespan and therefore life cycle metrics) and consumer safety. In this work, we studied both the safety and efficacy of a series of phenolic preservatives and compared them to common preservatives found in personal care products and building materials.
  • Evolution of 49 Phenolic Compounds in Shortly-Aged Red Wines Made from Cabernet Gernischt (Vitis Vinifera L

    Evolution of 49 Phenolic Compounds in Shortly-Aged Red Wines Made from Cabernet Gernischt (Vitis Vinifera L

    Food Sci. Biotechnol. Vol. 18, No. 4, pp. 1001 ~ 1012 (2009) ⓒ The Korean Society of Food Science and Technology Evolution of 49 Phenolic Compounds in Shortly-aged Red Wines Made from Cabernet Gernischt (Vitis vinifera L. cv.) Zheng Li, Qiu-Hong Pan, Zan-Min Jin, Jian-Jun He, Na-Na Liang, and Chang-Qing Duan* Center for Viticulture and Enology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, PR China Abstract A total of 49 phenolic compounds were identified from the aged red wines made from Cabernet Gernischt (Vitis vinifera L. cv.) grapes, a Chinese characteristic variety, including 13 anthocyanins, 4 pryanocyanins, 4 flavan-3-ol monomers, 6 flavan-3-ol polymers, 7 flavonols, 6 hydroxybenzoic acids, 5 hydroxycinnamic acids, 3 stilbenes, and 1 polymeric pigment. Evolution of these compounds was investigated in wines aged 1 to 13 months. Variance analysis showed that the levels of most phenolics existed significant difference in between wines aged 3 and 9 months. Cluster analysis indicated that 2 groups could be distinguished, one corresponding to wines aged 1 to 3 months and the other to wines aged 4 to 13 months. It was thus suggested that there were 2 key-stages for the development of fine wine quality, at the aged 3 and 9 months, respectively. This work would provide some helpful information for quality control in wine production. Keywords: Cabernet Gernischt, aged wine, phenolic compound, evolution, high performance liquid chromatography coupled with tandem mass spectrometry Introduction 3-ols in red wine and correlation with wine age (12), the evolutions of low molecular weight phenolic compounds Phenolic compounds in red wines mainly contain such as gallic acids and caffeic acids (13,14), as well as the anthocyanins, flavonols, flavan-3-ols, phenolic acids effects of oak barrel compounds and sorption behaviors on (including hydroxybenzoic acids and hydroxycinnamic evolution of phenolic compounds (15), have been reported.
  • Bio-Guided Fractionation of Extracts of Geranium Robertianum L.: Relationship MARK Between Phenolic Profile and Biological Activity ⁎ V.C

    Bio-Guided Fractionation of Extracts of Geranium Robertianum L.: Relationship MARK Between Phenolic Profile and Biological Activity ⁎ V.C

    Industrial Crops & Products 108 (2017) 543–552 Contents lists available at ScienceDirect Industrial Crops & Products journal homepage: www.elsevier.com/locate/indcrop Bio-guided fractionation of extracts of Geranium robertianum L.: Relationship MARK between phenolic profile and biological activity ⁎ V.C. Graçaa,b,c, Lillian Barrosb, Ricardo C. Calhelhab, Maria Inês Diasb, Isabel C.F.R. Ferreirab, , ⁎ P.F. Santosc, a Centre for Research and Technology of Agro-Environmental and Biological Sciences (CITAB) – Vila Real, University of Trás-os-Montes and Alto Douro, 5001-801 Vila Real, Portugal b Centro de Investigação de Montanha (CIMO), ESA, Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal c Chemistry Center – Vila Real (CQVR), University of Trás-os-Montes and Alto Douro, 5001-801 Vila Real, Portugal ARTICLE INFO ABSTRACT Keywords: Geranium robertianum L. is used in folk medicine and herbalism practice for the treatment of a variety of ail- Geranium robertianum L ments. Recently, we studied the bioactivity of several aqueous and organic extracts of this plant. In this work, the Fractionation more active extracts were fractionated and the fractions evaluated for their antioxidant activity and cytotoxicity Antioxidant activity against several human tumor cell lines and non-tumor porcine liver primary cells. Some of the fractions from the Antiproliferative activity acetone extract consistently displayed low EC and GI values and presented the higher contents of total Phenolic compounds 50 50 phenolic compounds in comparison to other fractions. The phenolic compounds profile of the fractions was determined. The bio-guided fractionation of the extracts resulted in several fractions with improved bioactivity relative to the corresponding extracts.
  • Use of Hydrolyzable Tannins for Treatement and Prophylaxis of AIDS

    Use of Hydrolyzable Tannins for Treatement and Prophylaxis of AIDS

    Europaisches Patentamt 0 297 547 /9i European Patent Office © Publication number: A2 Office europeen des brevets © EUROPEAN PATENT APPLICATION © Application number: 88110386.5 <r) mt. ci> A61K 31/70 © Date of filing: 29.06.88 The title of the invention has been amended © Applicant: LEAD CHEMICAL COMPANY LTD. (Guidelines for Examination in the EPO. A-lll, 77-3, Mimata Toyama-shi 7.3). Toyama-ken(JP) @ Inventor: Mori, Masao © Priority: 29.06.87 JP 161572/87 248, Tenshoji Toyama-shi Toyama-ken(JP) © Date of publication of application: Inventor: Koshiura, Ryozo 04.01.89 Bulletin 89/01 2-5-3, Mitsukuchi Shin-machi Kanazawa-shi Ishikawa-ken(JP) © Designated Contracting States: Inventor: Kurimura, Tadashi DE FR GB IT 110-1, Uchi-machi Yonago-sht Tottori-ken(JP) Inventor: Okuda, Takuo 3-4-25 Kitakata Okayama-shi Okayama-ken(JP) © Representative: Brauns, Hans-Adolf, Dr. rer. nat. et al Hoffmann, Eitle & Partner, Patentanwalte Arabellastrasse 4 D-8000 Munich 81 (DE) © Use of hydrolyzable tannins for treatement and prophylaxis of AIDS. © Disclosed is a medical composition for remedy of acquired immune deficiency syndrome (AIDS) and for prevention of manifestation of the symptoms of the disease, which comprises tannins containing monomers and oligomers of hydrolyzable tannins as an active ingredient. The medical composition can be administered by any route of peroral or parenteral administration. This may have an elevated infection-inhibiting action when used together with an antibody to HIV. CM < in CD CL LLj Xerox Copy Centre EP 0 297 547 A2 MEDICAL COMPOSITIONS FOR REMEDY OF ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS) AND FOR PREVENTION OF MANIFESTATION OF THE SYMPTOMS OF THE DISEASE Background of the Invention: 1 .
  • Antioxidant and in Vitro Preliminary Anti-Inflammatory

    Antioxidant and in Vitro Preliminary Anti-Inflammatory

    antioxidants Article Antioxidant and In Vitro Preliminary Anti-Inflammatory Activity of Castanea sativa (Italian Cultivar “Marrone di Roccadaspide” PGI) Burs, Leaves, and Chestnuts Extracts and Their Metabolite Profiles by LC-ESI/LTQOrbitrap/MS/MS Antonietta Cerulli 1, Assunta Napolitano 1, Jan Hošek 2 , Milena Masullo 1, Cosimo Pizza 1 and Sonia Piacente 1,* 1 Dipartimento di Farmacia, Università degli Studi di Salerno, via Giovanni Paolo II n. 132, I-84084 Fisciano, SA, Italy; [email protected] (A.C.); [email protected] (A.N.); [email protected] (M.M.); [email protected] (C.P.) 2 Department of Pharmacology and Toxicology, Veterinary Research Institute, Hudcova 296/70, 621 00 Brno, Czech Republic; [email protected] * Correspondence: [email protected]; Tel.: +39-089-969763; Fax: +39-089-969602 Abstract: The Italian “Marrone di Roccadaspide” (Castanea sativa), a labeled Protected Geograph- ical Indication (PGI) product, represents an important economic resource for the Italian market. With the aim to give an interesting opportunity to use chestnuts by-products for the development of nutraceutical and/or cosmetic formulations, the investigation of burs and leaves along with chestnuts of C. sativa, cultivar “Marrone di Roccadaspide”, has been performed. The phenolic, tannin, Citation: Cerulli, A.; Napolitano, A.; and flavonoid content of the MeOH extracts of “Marrone di Roccadaspide” burs, leaves, and chestnuts Hošek, J.; Masullo, M.; Pizza, C.; as well as their antioxidant activity by spectrophotometric methods (1,1-diphenyl-2-picrylhydrazyl Piacente, S. Antioxidant and In Vitro (DPPH), Trolox Equivalent Antioxidant Capacity (TEAC), and Ferric Reducing Antioxidant Power Preliminary Anti-Inflammatory Activity of Castanea sativa (Italian (FRAP) have been evaluated.
  • Exploring the Antioxidant Features of Polyphenols by Spectroscopic and Electrochemical Methods

    Exploring the Antioxidant Features of Polyphenols by Spectroscopic and Electrochemical Methods

    antioxidants Article Exploring the Antioxidant Features of Polyphenols by Spectroscopic and Electrochemical Methods Berta Alcalde, Mercè Granados and Javier Saurina * Department of Chemical Engineering and Analytical Chemistry, University of Barcelona, Martí i Franquès 1-11, 08028 Barcelona, Spain; [email protected] (B.A.); [email protected] (M.G.) * Correspondence: [email protected]; Tel.: +34-93-403-4873 Received: 16 October 2019; Accepted: 30 October 2019; Published: 31 October 2019 Abstract: This paper evaluates the antioxidant ability of polyphenols as a function of their chemical structures. Several common food indexes including Folin-Ciocalteau (FC), ferric reducing antioxidant power (FRAP) and trolox equivalent antioxidant capacity (TEAC) assays were applied to selected polyphenols that differ in the number and position of hydroxyl groups. Voltammetric assays with screen-printed carbon electrodes were also recorded in the range of 0.2 to 0.9 V (vs. Ag/AgCl − reference electrode) to investigate the oxidation behavior of these substances. Poor correlations among assays were obtained, meaning that the behavior of each compound varies in response to the different methods. However, we undertook a comprehensive study based on principal component analysis that evidenced clear patterns relating the structures of several compounds and their antioxidant activities. Keywords: antioxidant index; differential pulse voltammetry; polyphenols; index correlation; structure-activity 1. Introduction Epidemiological studies have shown that antioxidant molecules such as polyphenols may help in the prevention of cardiovascular and neurological diseases, cancer and aging-related disorders [1–4]. Antioxidants act against excessively high levels of free radicals, the harmful products of aerobic metabolism that can produce oxidative damage in the organism [5].