DOCSLIB.ORG

United States Patent (19) 11 Patent Number: 4,666,701 Horrobin Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
United States Patent (19) 11 Patent Number: 4,666,701 Horrobin Et Al United States Patent (19) 11 Patent Number: 4,666,701 Horrobin et al. 45) Date of Patent: May 19, 1987 54 PHARMACEUTICAL AND DIETARY 58) Field of Search .......................................... 424/10. COMPOSITIONS Primary Examiner-Stanley J. Friedman 75) Inventors: David F. Horrobin, Surrey, England; Attorney, Agent, or Firm-Nixon & Vanderhye Mehar S. Manku; Yung S. Huang, both of Nova Scotia, Canada 57) ABSTRACT Efamol Limited, Surrey, England Gamma-linolenic acid or dihomo-gamma-linolenic acid 73) Assignee: for use in the reduction or prevention of gastro-intesti (21) Appl. No.: 839,228 nal bleeding and other side effects shown by NSAIDs 22 Filed: Mar, 13, 1986 when administered on a continuing basis, including use in allowing said administration to be replaced by admin (30) Foreign Application Priority Data istration of said acid alone in arthritis and other condi Mar. 19, 1985 GB United Kingdom ................. 8507058 tions without exacerbation of symptoms. 51) Int. Cl. .............................................. A61K27/00 52 U.S. C. ...................................................... 424/10 5 Claims, No Drawings 4,666,701 1. 2 been found that the 22:4n-6 acid produced from arachi PHARMACEUTICAL AND DIETARY donic acid gives rise to a series of homo-2-series PGs, COMPOSITIONS though their importance is as yet unknown. DGLA is the key substance. GLA is almost com FIELD OF THE INVENTION pletely and very rapidly converted in the body to The invention relates in one aspect to the prevention DGLA and so for practical purposes the oral adminis or reduction of side effects of aspirin and other non tration of DGLA and GLA amounts to the same thing. steroidal anti-inflammatory drugs (NSAID), and in DGLA can be converted to a storage form or to PGs of another aspect to reduction or elimination of their use. 10 the 1-series or, through arachidonic acid, to PGs of the 2-series. GENERAL BACKGROUND Considering dietary requirements, it is well known, NSAID are very widely used in clinical medicine. There is a very large number of drugs in this group for example, that linoleic acid cannot be made by the including such compounds as aspirin, indomethacin, body and so must be taken in the diet. However, it has Diclofenac, Fenoprofen, flufenamic acid, mefenamic 15 been generally thought that the body can metabolise acid, flurbiprofen, ibuprofen, ketoprofen, naproxen, linoleic acid to all the other n-6 acids and therefore that phenylbutazone, piroxicam and sulindac. Although provided linoleic acid intake is adequate, no lack of the compounds with many different structures come into other n-6 acids will be found. this class it is believed that their common biological In previous patent applications (for example, Pub mechanism of action is inhibition of the formation o f 20 lished European Patent Application No. A 0 003 407, prostaglandins (PGs). The drugs can produce a very U.S. Pat. No. 4,273,763; Published European Patent wide range of side effects, the most common and consis Application No. A 0004770, U.S. Pat. No. 4,309,415; tent of which is gastro-intestinal bleeding. It is believed Published European Patent Application No. 0 019423, that the majority of these side effects, including the U.S. Pat. No. 4,388,324) it has, however been pointed bleeding, result from the inhibition of PG synthesis. 25 out that the first enzyme in the pathway, the delta-6 Although they are implicated in inflammation, PGs have many desirable actions, including a poorly under desaturase which, for example, converts linoleic acid to stood cytoprotective effect. PGs of the 1-series, derived gamma-linolenic acid, is not fully effective in a variety from DGLA, have particularly desirable actions but of conditions. The administration of gamma-linolenic unfortunately NSAID inhibit formation of these PGs as 30 acid or dihomo-gamma-linolenic acid or both has been well as the 2-series PGs and other compounds, of part suggested and has been successful in treating a number desirable, part undesirable effect, formed from arachi of clinical conditions. donic acid. In the above patent applications attention is primarily The outline of production of 1-series and 2-series PGs paid to the function of essential fatty acids in prosta in the body is believed to be as shown in the following 35 glandin (PG) metabolism and in particular to their role diagram: in securing a proper balance between 1-series and 2-ser ies PGs. cis-Linoleic Acid We are, however, becoming increasingly aware of (9,12-octadecadienoic acid) the significance of the essential fatty acids in them 40 selves, in which considerable general interest has been shown in recent years, primarily in the acids of the n-6 GLA series both as such and in relation to prostaglandin me (6,9,12-octadecatrienoic acid) tabolism, but also in the acids of the n-3 series. The n-6 45 acids in particular are required in the body for the struc ture of membranes in and around cells, being believed to be necessary for maintaining normal flexibility, fluidity esterDGLA S(8,11,14)-eicosarienoic DGLA acid)->1 endoperoxides series and permeability of such membranes. reset Ves The pathways of metabolism of the n-6 essential fatty (small) 50 acids and the related n-3 acids sharing, it is believed, series common enzymes in the two pathways, are: PG's Large AA AA ester (Arachidonic acid i.e. n-6 n-3 reserves 5,8,11,14-eicosatetraenoic acid) 55 18:2 delta-9,12 (linoleic acid) 18:3 delta-9,12,15 (alpha linolenic acid) 2 series t desaturase endoperoxides 60 18:3 delta-6,9,12 (gamma-linolenic 18:4 delta-6,9,12,15 acid) 2 series PG's e The broad outline of this pathway is well known, and 20:3 delta-8,11,14 (dihomo-gamma 20:4 delta-8, 1,14, 17 it brings out clearly that a major function of essential 65 linolenic acid) fatty acids is to act as precursors for prostaglandins, 1-series PGs being formed from DGLA and 2-series s desaturase PGs from arachidonic acid. Further, it has recently . 4,666,701 3. 4. ratio of DGLA products (1-series PGs) to arachidonic -continued acid products (2-series PGs) will therefore be increased. n-6 n-3 20:4 delta-5,8,11,14 (arachidonic 20:5 delta-5,8,11,14, 17 DISCOVERY BEHIND PRESENT INVENTION acid) We have discovered a new way of preventing or reducing the gastro-intestinal ulceration and bleeding which can occur in the presence of NSAID. We believe e that his depends on a hitherto unrecognised biological 22:4 delta-7,10,13,16 (adrenic acid) 22:5 delta-7,10,13,16,19 effect of NSAID and that the mechanism has general i- desaturase 10 relevance to many of the other side effects of NSAID. We have also found a method whereby patients can be 22:5 delta-4,7,10,13,16 22:6 deta-4,7,10,13,16,19 withdrawn from treatment with NSAID without any exacerbation of their symptoms and we believe that this The pathways are not normally reversible nor, in man, will prove of major therapeutic value, since GLA and are n-3 and n-6 series acids interconvertible. 5 DGLA are inherently much safer to administer than the The acids, which naturally are of the all-cis configu NSAIDS. In experimental work five male and five female nor ration, are systematically named as derivatives of the mal adult humans in their 20s were each given 1200 mg corresponding octadecanoic, eicosanoic or docosanoic per day of soluble aspirin for a period of seven days. acids e.g. delta-9,12-octadecadienoic acid or delta 20 Blood for measurement (by the method of Pelick et al, 4,7,10,13,16, 19 docosahexaenoic acid, but numerical cited later herein) of fatty acids in plasma was taken designation such as, correspondingly, 18:2 n-6 or 22:6 before starting treatment and on the seventh day. No n-3 is convenient. Initials, for example, DHA for 22:6 consistent change with regard to many fatty acids oc n-3 (docosahexaenoic acid), are also used but do not curred but with linoleic acid and its metabolite gamma serve when n-3 and n-6 acids of the same chain length 25 and degree of unsaturation exist. Trivial names in more linolenic acid (GLA) the following were found: or less common use in the n-6 series are as shown. Of the n-3 series only 18:3 n-3 has a commonly used trivial Linoleic/ GLA name, alpha-linolenic acid. It was characterised earlier Linoleic Acid GLA Ratio than gamma-linolenic acid and reference in the litera 30 ture simply to linolenic acid, especially in the earlier Total plasma lipid: Before Aspirin 25.18 - 4.40 0.30 - 0.27 85 literature, is to the alpha-acid. After Aspirin 27.99 5.9 0.10 - 0.19 280 In the body, the n-3 acids are metabolised preferen Cholesterol ester fraction: tially and as a result, in plasma for example, levels of Before Aspirin 52.14 6.48 0.55 - 0.60 95 alpha-linolenic acid (18:3n-3) are low and 18:4n-3 and 35 After Aspirin 56.81 - 4.26 0.6 - 0.46 355 20:4n-3 are in trace amounts only. In contrast the n-6 Phospholipid fraction: acids are normally present in moderate amounts, though Before Aspirin 24.26 4.0 0.48 - 0.09 50.5 gamma-linolenic acid (GLA) is at low levels, being After Aspirin 26.48 4.92 0.18 0.05 147 apparently converted to dihomo-gamma-linolenic acid (DGLA) more rapidly than its relatively slow produc 40 It can be seen that in each case linoleic acid levels went tion from linoleic acid.
Load more

Recommended publications
  • Types of Gene Effects Governing the Inheritance of Oleic and Linoleic Acids in Peanut (Arachis Hypogaea L.)
    African Journal of Biotechnology Vol. 11(67), pp. 13147-13152, 21 August, 2012 Available online at http://www.academicjournals.org/AJB DOI:10.5897/AJB12.1498 ISSN 1684-5315 ©2012 Academic Journals Full Length Research Paper Types of gene effects governing the inheritance of oleic and linoleic acids in peanut (Arachis hypogaea L.) Nattawut Singkham1, Sanun Jogloy1*, Bhalang Suriharn1, Thawan Kesmala1, Prasan Swatsitang2, Prasit Jaisil1, Naveen Puppala3 and Aran Patanothai1 1Department of Plant Science and Agricultural Resources, Faculty of Agriculture, Khon Kaen University, Khon Kaen, 40002, Thailand. 2Department of Biochemistry, Faculty of Science, Khon Kaen University, Khon Kaen, 40002, Thailand. 3Agricultural Science Center at Clovis, New Mexico State University, Clovis, New Mexico, 88101, USA. Accepted 3 August, 2012 Oleic and linoleic acids are major fatty acids in peanut determining the quality and shelf-life of peanut products. A better understanding on the inheritance of these characters is an important for high-oleic breeding programs. The objective of this research was to determine the gene actions for oleic acid, linoleic acid, the ratio of oleic to linoleic acids (O/L ratio) and percentage oil (% oil) in peanut. Georgia- 02C, SunOleic 97R (high-oleic genotypes) and KKU 1 (low-oleic genotypes) were used as parents to generate P1, P2, F2, F3, BC11S and BC12S. The entries were planted in a randomized complete block design with four replications in the rainy season (2008) and the dry season (2008/2009). Gas liquid chromatography (GLC) was used to analyze fatty acid compositions. The data were used in generation means analysis to understand gene effects. The differences in season, generation and generation season interactions were significant for oleic acid in the crosses Georgia-02C KKU 1 and SunOleic 97R KKU 1.
    [Show full text]
  • Fatty Acids: Essential…Therapeutic
    Volume 3, No.2 May/June 2000 A CONCISE UPDATE OF IMPORTANT ISSUES CONCERNING NATURAL HEALTH INGREDIENTS Written and Edited By: Thomas G. Guilliams Ph.D. FATTY ACIDS: Essential...Therapeutic Few things have been as confusing to both patient and health care provider as the issue of fats and oils. Of all the essential nutrients required for optimal health, fatty acids have not only been forgotten they have been considered hazardous. Health has somehow been equated with “low-fat” or “fat-free” for so long, to suggest that fats could be essential or even therapeutic is to risk credibility. We hope to give a view of fats that is both balanced and scientific. This review will cover the basics of most fats that will be encountered in dietary or supplemental protocols. Recommendations to view essential fatty acids in a similar fashion as essential vitamins and minerals will be combined with therapeutic protocols for conditions ranging from cardiovascular disease, skin conditions, diabetes, nerve related disorders, retinal disorders and more. A complete restoration of health cannot be accomplished until there is a restoration of fatty acid nutritional information among health care professionals and their patients. Fats- What are they? Dietary fats come to us from a variety of sources, but primarily in the form of triglycerides. That is, three fatty acid molecules connected by a glycerol backbone (see fatty acid primer page 3 for diagram). These fatty acids are then used as energy by our cells or modified into phospholipids to be used as cell or organelle membranes. Some fatty acids are used in lipoprotein molecules to shuttle cholesterol and fats to and from cells, and fats may also be stored for later use.
    [Show full text]
  • Use of Gamma-Linolenic Acid and Related Compounds for the Manufacture of a Medicament for the Treatment of Endometriosis
    ~" ' MM II II II II I II Ml Ml Ml I II I II J European Patent Office ooo Ats*% n i © Publication number: 0 222 483 B1 Office_„. europeen des brevets © EUROPEAN PATENT SPECIFICATION © Date of publication of patent specification: 18.03.92 © Int. CI.5: A61 K 31/20, A61 K 31/1 6, A61K 31/23 © Application number: 86307533.9 @ Date of filing: 01.10.86 Use of gamma-linolenic acid and related compounds for the manufacture of a medicament for the treatment of endometriosis. © Priority: 02.10.85 GB 8524276 © Proprietor: EFAMOL HOLDINGS PLC Efamol House Woodbridge Meadows @ Date of publication of application: Guildford Surrey GU1 1BA(GB) 20.05.87 Bulletin 87/21 @ Inventor: Horrobin, David Frederick © Publication of the grant of the patent: c/o Efamol Ltd, Efamol House Woodbridge 18.03.92 Bulletin 92/12 Meadows Guildford, Surrey, GU1 1BA(GB) © Designated Contracting States: Inventor: Casper, Robert AT BE CH DE ES FR GB GR IT LI LU NL SE University Hospital 339 Windermere Road London Ontario N6A 5AS(CA) © References cited: EP-A- 0 003 407 EP-A- 0 115 419 © Representative: Miller, Joseph EP-A- 0 132 089 J. MILLER & CO. Lincoln House 296-302 High EP-A- 0 181 689 Holborn London WC1V 7JH(GB) J. GYNECOL. OBSTET. BIOL. REPROD. vol. 10, no. 5, 1981, pages 465-471 Masson, Paris, FR PH. CALLGARIS et al.: "Endometriose de la paroi abdominale" 00 00 CLINICAL OBSTETRICS AND GYNECOLOGY, 00 vol. 23, no. 3, Sept. 1980, pages 895-900 J.C. WEED: "Prostaglandins as related to en- CM dometriosis" CM CM Note: Within nine months from the publication of the mention of the grant of the European patent, any person may give notice to the European Patent Office of opposition to the European patent granted.
    [Show full text]
  • Role of Arachidonic Acid and Its Metabolites in the Biological and Clinical Manifestations of Idiopathic Nephrotic Syndrome
    International Journal of Molecular Sciences Review Role of Arachidonic Acid and Its Metabolites in the Biological and Clinical Manifestations of Idiopathic Nephrotic Syndrome Stefano Turolo 1,* , Alberto Edefonti 1 , Alessandra Mazzocchi 2, Marie Louise Syren 2, William Morello 1, Carlo Agostoni 2,3 and Giovanni Montini 1,2 1 Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico, Pediatric Nephrology, Dialysis and Transplant Unit, Via della Commenda 9, 20122 Milan, Italy; [email protected] (A.E.); [email protected] (W.M.); [email protected] (G.M.) 2 Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy; [email protected] (A.M.); [email protected] (M.L.S.); [email protected] (C.A.) 3 Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Pediatric Intermediate Care Unit, 20122 Milan, Italy * Correspondence: [email protected] Abstract: Studies concerning the role of arachidonic acid (AA) and its metabolites in kidney disease are scarce, and this applies in particular to idiopathic nephrotic syndrome (INS). INS is one of the most frequent glomerular diseases in childhood; it is characterized by T-lymphocyte dysfunction, alterations of pro- and anti-coagulant factor levels, and increased platelet count and aggregation, leading to thrombophilia. AA and its metabolites are involved in several biological processes. Herein, Citation: Turolo, S.; Edefonti, A.; we describe the main fields where they may play a significant role, particularly as it pertains to their Mazzocchi, A.; Syren, M.L.; effects on the kidney and the mechanisms underlying INS. AA and its metabolites influence cell Morello, W.; Agostoni, C.; Montini, G.
    [Show full text]
  • On Fatty Acid Composition and Shelf Life of Broiler Chicken Meat Hilal Ürüşan1* • Canan Bölükbaşı2
    Alinteri J. of Agr. Sci. (2020) 35(1): 29-35 http://dergipark.gov.tr/alinterizbd e-ISSN: 2587-2249 http://www.alinteridergisi.com/ [email protected] DOI: 10.28955/alinterizbd.737995 RESEARCH ARTICLE The Influence of Turmeric Powder (Curcuma longa) on Fatty Acid Composition and Shelf Life of Broiler Chicken Meat Hilal Ürüşan1* • Canan Bölükbaşı2 1Atatürk University, Erzurum Vocational High School, Department of Plant and Animal Production, Erzurum/Turkey 2Atatürk University, Faculty of Agriculture, Department of Animal Science, Erzurum/Turkey ARTICLE INFO ABSTRACT Article History: The objective of this study was to determine the appropriate concentration of dietary Received: 21.03.2019 supplementation of turmeric powder, and its effect on thiobarbituric acid reactive substance (TBARS) Accepted: 03.02.2020 and fatty acid composition in thigh and breast meat of broiler chickens. Three hundred fifty (175 Available Online: 15.05.2020 male and 175 female), one day old Ross-308 broiler chicks were used in this study. A corn-soybean Keywords: meal based diet containing different levels of turmeric powder (0, 2, 4, 6, 8, 10 g/kg) and a single dose of chlortetracycline (10 mg/kg) was used. The result revealed that dietary supplementation of Broiler 2, 4, 6, 8 and 10 g/kg of turmeric powder decreased TBARS in thigh meat at 5th day when compared Turmeric with control. The addition of 4 g/kg turmeric powder to the basal diet increased DHA, SFA and omega- TBARS 3 in breast meat. DHA and SFA were increased by dietary 2 g/kg turmeric powder in thigh meats. Fatty acid composition Under the conditions of this experiment, it was concluded that turmeric powder may positive effects Antioxidant on tissue fatty acid compositions and shelf life of meat (TBARS).
    [Show full text]
  • Production of 8,11,14,17-Cis-Eicosatetraenoic Acid
    Production of 8,11,14,17-cis-Eicosatetraenoic Acid (20:4ω-3) by a ∆5 and ∆12 Desaturase-Defective Mutant of an Arachidonic Acid-Producing Fungus Mortierella alpina 1S-4 Hiroshi Kawashimaa, Eiji Sakuradanib, Nozomu Kamadab, Kengo Akimotoa, Kyoko Konishia, Jun Ogawab, and Sakayu Shimizub,* aInstitute for Biomedical Research, Suntory Ltd., Shimamoto-cho, Osaka 618-0001, Japan, and bDivision of Applied Life Sci- ences, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan ∆ ∆ ABSTRACT: A 5 and 12 desaturase-defective mutant of an there are large amounts of other C20 PUFA, such as AA, EPA, arachidonic acid-producing fungus, Mortierella alpina 1S-4, pro- and dihomo-γ-linolenic acid (DGLA), which are difficult to duced 8,11,14,17-cis-eicosatetraenoic acid (20:4ω3) intracellu- separate from 20:4ω3. During our studies on PUFA production larly when grown with linseed oil. Dihomo-γ-linolenic acid was involving AA-producing Mortierella fungi, we found 20:4ω3 the only C20 polyunsaturated fatty acid (4.9 wt% of total mycelial was formed (ca. 0.5 mg/mL of culture medium) as a by-prod- ω fatty acids) other than 20:4 3. AA and 5,8,11,14,17-cis-eicosapen- uct (3). Large amounts of AA (2.44 mg/mL) and EPA (1.88 taenoic acid were not detected. The mycelial lipids consisted of mg/mL) were produced in this case. Recently, we reported 82.2% (by mol) triacylglycerol (TG), 7.1% diacylglycerol, 8.9% ω ∆ phospholipids (PL), and 1.9% free fatty acids. The percentage of 20:4 3 production by cultivating 5 desaturase-defective mu- 20:4ω3 was higher in PL (30.1%) than in TG (11.6%), and highest tants of AA-producing M.
    [Show full text]
  • Omega 3 Fatty Acids and Health
    Dietary n-6 and n-3 fatty acids: health and disease Professor Asim K. Duttaroy Department of Nutrition Room No. 2199 Tel: 22 85 15 47 Email: [email protected] Type of Dietary Fatty Acids Saturated fatty acids (Palmitic acid, 16:0, Stearic acid, 18:0) Monounsaturated fatty acids (Palmiteloic acid, 16:1,n-7, Oleic acid, 18:1n-9) Polyunsaturated fatty acids (Linoleic acid, 18:2,n-6, Alpha linolenic acid, 18:3n-3) Essential Fatty acids (EFA) Long chain polyunsaturated fatty acids Arachidonic acid, 20:4n-6, Eicosapentaenoic acid, 20:5n-3, Docosahexaenoic acid, 22:6n-3 Essential Fatty acids Linoleic acid, 18:2n-6 COOH Alpha linolenic acid, 18:3n-3 COOH Metabolic Conversions of Essential Fatty Acids in Mammals N6-Series N3-Series Linoleic (18:2) α-linolenic (18:3) Δ6-desaturase γ-linolenic (18:3) Octadecatetraenoic (18:4) Elongase Dihomo−γ−linolenic (20:3) Eicosatetraenoic (20:4) Δ5-desaturase Arachidonic (20:4) Eicosapentaenoic (20:5) Elongase Adrenic (22:4) Docosapentaenoic (22:5) Elongase Tetracosatetraenoic (24:4) Tetracosapentaenoic (24:5) Δ6-desaturase Tetracosapentaenoic (24:5) Tetracosahexaenoic (24:6) β-oxidation Docosapentaenoic (22:5) (Peroxisome) Docosahexaenoic (22:6) Contributions of dietary fats to PUFA Metabolism Seed oils Sunflower, N-6 fatty acids N-6 fatty acids Flaxseed oils Safflower, Peanut Linoleic acid 18:2 α Linolenic acid, 18:3 Green leaves Evening Octadecatetraenoic acid, 18:4 Primrose, γ Linolenic acid 18:3 Borage oil Eicosatetraenoic acid,20:4 Fish, Dihomo γ Linolenic acid 20:3 Egg Eicosapentaenoic acid,20:5
    [Show full text]
  • A Role for the Orphan Human Cytochrome P450 2S1 in Polyunsaturated Fatty Acid V-1 Hydroxylation Using an Untargeted Metabolomic Approach S
    Supplemental material to this article can be found at: http://dmd.aspetjournals.org/content/suppl/2019/09/11/dmd.119.089086.DC1 1521-009X/47/11/1325–1332$35.00 https://doi.org/10.1124/dmd.119.089086 DRUG METABOLISM AND DISPOSITION Drug Metab Dispos 47:1325–1332, November 2019 Copyright ª 2019 by The American Society for Pharmacology and Experimental Therapeutics A Role for the Orphan Human Cytochrome P450 2S1 in Polyunsaturated Fatty Acid v-1 Hydroxylation Using an Untargeted Metabolomic Approach s Mostafa I. Fekry, Yi Xiao,1 Jeannette Zinggeler Berg,2 and F. Peter Guengerich Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee (M.I.F., Y.X., J.Z.B., F.P.G.); and Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo, Egypt (M.I.F.) Received August 16, 2019; accepted September 6, 2019 ABSTRACT Cytochrome P450 (P450) 2S1 is one of the orphan P450s, known to of hydroxylation were slow, but no detectable activity was seen with be expressed but not having a defined function with an endogenous either medium-chain length or saturated fatty acids. P450 2S1 is Downloaded from substrate or in drug oxidations. Although it has been clearly known to be expressed, at least at the mRNA level, to the extent of demonstrated to catalyze reductive reactions, its role in NADPH- some other non-3A subfamily P450s in the human gastrointestinal dependent oxidations has been ambiguous. In our efforts to tract, and the activity may be relevant. We conclude that P450 2S1 is characterize orphan human P450 enzymes, we used an untargeted afattyacidv-1 hydroxylase, although the physiologic relevance of liquid chromatography-mass spectromterymetabolomic approach these oxidations remains to be established.
    [Show full text]
  • Curcumin Boosts DHA in the Brain: Implications for the Prevention of Anxiety Disorders
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Biochimica et Biophysica Acta 1852 (2015) 951–961 Contents lists available at ScienceDirect Biochimica et Biophysica Acta journal homepage: www.elsevier.com/locate/bbadis Curcumin boosts DHA in the brain: Implications for the prevention of anxiety disorders Aiguo Wu a, Emily E. Noble a,EthikaTyagia,ZheYinga, Yumei Zhuang a, Fernando Gomez-Pinilla a,b,⁎ a Department of Integrative Biology and Physiology, University of California at Los Angeles, 621 Charles E. Young Drive Los Angeles, CA 90095, USA b Department of Neurosurgery, UCLA Brain Injury Research Center, David Geffen School of medicine at UCLA, Los Angeles, CA 90095, USA article info abstract Article history: Dietary deficiency of docosahexaenoic acid (C22:6 n-3; DHA) is linked to the neuropathology of several cognitive Received 3 September 2014 disorders, including anxiety. DHA, which is essential for brain development and protection, is primarily obtained Received in revised form 17 November 2014 through the diet or synthesized from dietary precursors, however the conversion efficiency is low. Curcumin Accepted 2 December 2014 (diferuloylmethane), which is a principal component of the spice turmeric, complements the action of DHA in Available online 27 December 2014 the brain, and this study was performed to determine molecular mechanisms involved. We report that curcumin α Keywords: enhances the synthesis of DHA from its precursor, -linolenic acid (C18:3 n-3; ALA) and elevates levels of DHA synthesis enzymes involved in the synthesis of DHA such as FADS2 and elongase 2 in both liver and brain tissues.
    [Show full text]
  • Leveraging CAM to Treat Depression and Anxiety
    Amanda E. Olagunju, DO; Leveraging CAM to treat Heidi Gaddey, MD Department of Family Medicine, Langley Hospital, depression and anxiety Langley Air Force Base, VA (Dr. Olagunju); Department of Family Medicine, David Grant Conventional medications and psychotherapy are still Medical Center, Travis Air Force Base, CA (Dr. Gaddey) first-line treatments, but certain complementary and amanda.olagunju@gmail. alternative strategies have value as adjunctive measures. com The authors reported no potential conflict of interest relevant to this article. The views expressed in this article lmost 8% of Americans ages ≥ 12 years have depression are those of the authors and do not PRACTICE necessarily reflect the official policy and 19.1% of Americans ages ≥ 18 years have experienced or position of the US government or any other agency, organization, RECOMMENDATIONS 1,2 an anxiety disorder in the past year. Furthermore, sui- employer, or company. ❯ Consider standardized A cide, which can result from depression and anxiety, is the 10th preparations of St. John’s leading cause of death in the United States, claiming about 40,000 wort for the treatment of 3 mild to moderate depression to 49,000 lives per year since 2012, with increasing yearly rates. in certain patients. A While multiple conventional medication and therapy treatments are available, patients remain interested in complementary and ❯ Encourage patients with alternative medicine (CAM) options. According to the National depression or anxiety to engage in exercise and Center for Complementary and Integrative Health, more than 30% 4 meditation to help with of American adults use CAM treatments. symptom management. A This article provides an overview of the evidence for com- monly used CAM treatments for unipolar depression and anxiety ❯ Consider methylfolate in adults.
    [Show full text]
  • Linoleic Acid: the Code of Life?
    Journal of ISSN: 2581-7310 Inno Volume 1: 2 Health Science and Development J Health Sci Dev 2018 Linoleic Acid: The Code of Life? Joseph Eldor1* 1Joseph Eldor, Theoretical Medicine Institute, Jerusalem, Israel Abstract Article Information Intralipid® 20% is made up of 20% Soybean Oil, 1.2% Egg Yolk Article Type: : Research Phospholipids, 2.25% Glycerine, and Water for Injection. The major Article Number: JHSD114 component fatty acids are linoleic acid (44-62%), oleic acid (19-30%), Received Date: 30 August, 2018 palmitic acid (7-14%), a-linolenic acid (4-11%) and stearic acid (1.4- Accepted Date: 26 September, 2018 5.5%). It means that the various effects of Intralipid are based 63% to Published Date: 10 September, 2018 92% on linoleic acid and oleic acid. *Corresponding author: Joseph Eldor, Theoretical Are these 2 fatty acids the Code of Life? Medicine Institute, Jerusalem, Israel, Tel: +972-2-5835528; Email: csen_international(at)csen.com Linoleic acid has effects on the mitochondria. Linoleic acid has effects on Cancer. Linoleic acid has effects on Aging. Citation: Eldor J (2018) Linoleic Acid: The Code of Life?. Keywords Linoleic acid, Oleic acid, Intralipid, Mitochondria, Cancer, J Health Sci Dev Vol: 1, Issu: 2 (18-32). Aging. The Basis of Intralipid Copyright: © 2018 Eldor J. This is an open-access article Intralipid® 20% (A 20% I.V. Fat Emulsion) Pharmacy Bulk Package distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, is a sterile, non-pyrogenic fat emulsion intended as a source of calories distribution, and reproduction in any medium, provided the and essential fatty acids for use in a pharmacy ad- mixture program.
    [Show full text]
  • Beneficial Outcomes of Omega-6 and Omega-3 Polyunsaturated Fatty
    nutrients Review Beneficial Outcomes of Omega-6 and Omega-3 Polyunsaturated Fatty Acids on Human Health: An Update for 2021 Ivana Djuricic 1 and Philip C. Calder 2,3,* 1 Department of Bromatology, Faculty of Pharmacy, University of Belgrade, 11221 Belgrade, Serbia; [email protected] 2 School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK 3 NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton SO16 6YD, UK * Correspondence: [email protected] Abstract: Oxidative stress and inflammation have been recognized as important contributors to the risk of chronic non-communicable diseases. Polyunsaturated fatty acids (PUFAs) may regulate the antioxidant signaling pathway and modulate inflammatory processes. They also influence hepatic lipid metabolism and physiological responses of other organs, including the heart. Longitudinal prospective cohort studies demonstrate that there is an association between moderate intake of the omega-6 PUFA linoleic acid and lower risk of cardiovascular diseases (CVDs), most likely as a result of lower blood cholesterol concentration. Current evidence suggests that increasing intake of arachidonic acid (up to 1500 mg/day) has no adverse effect on platelet aggregation and blood clotting, immune function and markers of inflammation, but may benefit muscle and cognitive performance. Many studies show that higher intakes of omega-3 PUFAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are associated with a lower incidence of chronic diseases characterized Citation: Djuricic, I.; Calder, P.C. by elevated inflammation, including CVDs. This is because of the multiple molecular and cellular Beneficial Outcomes of Omega-6 and actions of EPA and DHA.
    [Show full text]