DOCSLIB.ORG

(2) Patent Application Publication (10) Pub. No.: US 2010/0056463 A1 Raederstorff Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(2) Patent Application Publication (10) Pub. No.: US 2010/0056463 A1 Raederstorff Et Al US 2010.0056463A1 (19) United States (2) Patent Application Publication (10) Pub. No.: US 2010/0056463 A1 Raederstorff et al. (43) Pub. Date: Mar. 4, 2010 (54) NOVEL COMPOSITIONS (30) Foreign Application Priority Data (76) Inventors: Daniel Raederstorff, Flaxlanden Jul. 14, 2006 (EP) .................................. 060.14645.3 (FR);(FR), JosephNathalie Schwager, Richard, BaselMulhouse Publication- - - Classificatione e (CH); Karin Wertz, Rheinfelden (51) Int. Cl. (DE) A61 K. 3 1/7004 (2006.01) C d Add A61 K 3.1/05 (2006.01) NIXONorrespondence & VANDERHYE, I eSS. PC (52) U.S. Cl. ........................................... 514/23:- 514/734 901 NORTH GLEBE ROAD, 11TH FLOOR (57) ABSTRACT ARLINGTON, VA 22203 (US) The present invention relates to novel compositions compris (21) Appl. No.: 12/373,584 ing hydroxytyrosol and/or oleuropein (I) and at least one additional component e.g. selected from the group of ligustil (22) PCT Filed: Jul. 12, 2007 ide, oleuropeinaglycone, magnolol, honokiol, genistein, res veratrol, EGCG, magnolia bark extract, cashew fruit extract (86) PCT No.: PCT/EP2007/006.188 and Glycyrrhiza foetida as well as to the use of these compo sitions as a medicament, in particular as a medicament for the § 371 (c)(1), treatment, co-treatment or prevention of inflammatory disor (2), (4) Date: Nov. 4, 2009 ders. Patent Application Publication Mar. 4, 2010 US 2010/0056463 A1 (I) (II) (III) Figure I US 2010/0056463 A1 Mar. 4, 2010 NOVEL COMPOSITIONS neurodermitis, thermal and radiation burns such as sunburn, other types of skin inflammation, and the tissue-degenerating effects of aging) and chronic inflammatory disorders, such as [0001] The present invention relates to novel compositions atherosclerosis, heart diseases, metabolic syndrome X, can comprising hydroxytyrosol and/or oleuropein (I) and at least cer, Alzheimer’s disease and pre-stages thereof such as mild one additional component selected from the group of ligustil cognitive impairment or photoageing which is associated ide, oleuropeinaglycone (II), tyrosol, extract from the bark of with chronic skin inflammation. Magnolia officinalis, magnolol, honokiol, genistein, resvera [0005] Rheumatoid arthritis is a chronic inflammatory dis trol, EGCG, methylsulfonylmethane, SAMe, collagen ease of the joints and is one of many different forms of hydrolysate, collagen, ascorbyl phosphate, lycopene, lutein, arthritis. For example, arthritis includes rheumatoid arthritis, zeaxanthin, fl-cryptoxanthin, Devil’s Claw, milk protein con spondyloarthopathies, gouty arthritis, osteoarthritis, sys centrate, solubilized keratin, celery seed extract, cetylated temic lupus erythematosus and juvenile arthritis. Like fatty acids, carnitine, thymoquinone, 2-hydroxy-4-methoxy asthma, rheumatoid arthritis is characterized at the molecular 3-(2-hydroxy-3-methyl-3-butenyl)-6-(2-phenylethyl)-ben level by chronically unbalanced expression of cytokines, zoic acid (III), Amorfrutin B (IV), Amorfrutin A (V), 2-hy chemokines, kinins and their receptors, adhesion molecules droxy-4-methoxy-3-(3-methyl-2-butenyl)-6-pentyl-benzoic and their respective receptors, as well as inflammatory acid (VI), cannabigerolic acid monomethyl ether (VII), 2-hy enzymes. droxy-4-methoxy-3-(2-hydroxy-3-methyl-3-butenyl)-6-pen [0006] Psoriasis is one of the most common skin problems, tyl-benzoic acid (VIII), 3-methoxy-2-(3-methyl-2-butenyl) affecting 1-3% of the human population. Inflammatory bowel 5-(2-phenylethyl)-phenol (IX), the compound offormula (X) disease is a general term used to describe gastrointestinal tract and 2-hydroxy-4-methoxy-5-(2-hydroxy-3-methyl-3-bute diseases and includes disorders such as ulcerative colitis and nyl)-6-(2-phenylethyl)-benzoic acid (XI), cardol diene (XII), Crohn’s disease. cardol triene (XIII), cashew fruit extract, boswellic acid, car [0007] Beside the process of intravascular lipid deposition, nosic acid, ursolic acid, horse chestnut extract, diosmetin, inflammatory reactions of the endothelial (i.e. blood vessel) tryptanthrin, diosgenin, curcumin and derivatives, Glycyr wall are considered to critically contribute to atherosclerosis rhiza foetida and white willow bark extract as well as to the i.e. atheroma formation. Atherosclerosis results from vascu use of these compositions as a medicament, in particular as a lar injury which triggers inflammation. Activated macroph medicament for the treatment, co-treatment or prevention of ages, T-lymphocytes, and eventually smooth muscle cells are inflammatory disorders. present in atherosclerotic plaques. Monocyte/macrophage [0002] Inflammatory disorders are one of the most impor and lymphocyte activation leads to the release of eicosanoids, tant health problems in the world. Inflammation is in general cytokines and matrix metalloproteinases (MMPs) which are a localized protective response of the body tissues to invasion implicated in endothelial damage, as well as in the formation of the host by foreign material orinjurious stimuli. The causes and eventually the rupture of atherosclerotic plaques. Finally, of inflammation can be infectious agents such as bacteria, circulating inflammatory markers such as C-reactive protein viruses, and parasites; or physical agents such as burns or (CRP), fibrinogen, and interleukins are increased or altered in radiation; or chemicals like toxins, drugs orindustrial agents; groups at high-risk of coronary artery diseases (CAD). Sev or immunological reactions such as allergies and autoim eral clinical trials indicate that elevated CRP concentration mune responses or conditions associated with oxidative correlates with increased risk of coronary, and vascular StreSS. events. Thus inflammation appears to play an important role [0003] Inflammation is characterized by pain, redness, in the initiation and progression of atheroma formation. swelling, heat, and eventual loss of function of the affected [0008] Inflammatory processes are also associated with the area. These symptoms are the results of a complex series of pathophysiology of Alzheimer’s disease. There is evidence of interactions mainly taking place between the cells of the inflammation in the brain of patients with Alzheimer’s dis immune system. The response of the cells results in an inter ease, as it is characterized by increased levels of cytokines acting network of several groups of inflammatory mediators: and activated microglial cells. Thus, inflammation is not only Proteins (e.g., cytokines, enzymes [e.g., proteases, peroxy involved in the classical inflammatory disorders (e.g., arthri dase], major basic protein, adhesion molecules [ICAM, tis, asthma, bowel diseases) but is also associated with many VCAMI), lipid mediators (e.g., eicosanoids, prostaglandins, chronic inflammatory disorders (e.g., atherosclerosis, heart leukotrienes, platelet activating factor [PAF]), reactive oxy diseases, metabolic syndrome X, cancer, Alzheimer disease). gen species (e.g., hydroperoxides, superoxyde anion O2–, [0009] Inflammatory events are also associated with the nitric oxide [NO] etc). However, many of those mediators of pathophysiology of different types of cancers (e.g. gastric and inflammation are also regulators of normal cellular activity. intestinal cancers, melanomas). Increased levels of inflam Thus, deficiencies of inflammatory reactions lead to a com matory mediators such as prostaglandins have been found in promised host (i.e. infection) while uncontrolled and thus cancers of breast, colon, lung and pancreas in humans. chronic inflammation leads to inflammatory diseases medi [0010] Currently, two main classes of drugs, the corticos ated in part by the excessive production of several of the teroid and the nonsteroidal anti-inflammatory drugs above mentioned mediators. (NSAIDs) are used to treat inflammatory disorders. NSAIDs [0004] Acute and chronic inflammation resulting from an and corticosteroids provide essentially symptomatic relief. excessive biosynthesis of inflammatory mediators is involved Use of corticosteroids has declined due to a growing concern in numerous inflammatory disorders such as arthritis (e.g. about the serious side effects of prolonged use. osteoarthritis, rheumatoid arthritis), asthma, inflammatory [0011) NSAIDs are among the most widely used drugs, bowel diseases, inflammatory diseases of the skin (e.g. con primarily for the treatment of pain and inflammatory disor tact dermatitis [particularly diaper area dermatitis], atopic ders, in particular for the treatment of arthritis (i.e. pain dermatitis, xerosis, eczema, rosacea, seborrhea, psoriasis, relief). Epidemiological studies have suggested that patients US 2010/0056463 A1 Mar. 4, 2010 taking NSAIDs have a lower risk of developing Alzheimer’s ment selected from the group of ligustilide, magnolol, disease than those not taking NSAIDs. A protective effect of genistein, resveratrol, EGCG, magnolia bark extract, cashew NSAIDs suggests that the cyclooxygenases might be fruit extract and Glycyrrhiza foetida. In a most preferred involved in the neurodegenerative process. Epidemiological embodiment, the invention relates to a composition compris studies showed a significant reduction in the risk of colorec ing hydroxytyrosol and/or oleuropein (I), in particular tal, gastric, esophageal, and breast cancers among people who hydroxytyrosol, and at least one additional component take NSAIDs compared with those not taking NSAIDs. In selected from the group of ligustilide, honokiol, genistein, animal models, NSAIDs significantly reduced tumor devel resveratrol and EGCG.
Load more

Recommended publications
  • Herbal Insomnia Medications That Target Gabaergic Systems: a Review of the Psychopharmacological Evidence
    Send Orders for Reprints to [email protected] Current Neuropharmacology, 2014, 12, 000-000 1 Herbal Insomnia Medications that Target GABAergic Systems: A Review of the Psychopharmacological Evidence Yuan Shia, Jing-Wen Donga, Jiang-He Zhaob, Li-Na Tanga and Jian-Jun Zhanga,* aState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China; bDepartment of Pharmacology, School of Marine, Shandong University, Weihai, P.R. China Abstract: Insomnia is a common sleep disorder which is prevalent in women and the elderly. Current insomnia drugs mainly target the -aminobutyric acid (GABA) receptor, melatonin receptor, histamine receptor, orexin, and serotonin receptor. GABAA receptor modulators are ordinarily used to manage insomnia, but they are known to affect sleep maintenance, including residual effects, tolerance, and dependence. In an effort to discover new drugs that relieve insomnia symptoms while avoiding side effects, numerous studies focusing on the neurotransmitter GABA and herbal medicines have been conducted. Traditional herbal medicines, such as Piper methysticum and the seed of Zizyphus jujuba Mill var. spinosa, have been widely reported to improve sleep and other mental disorders. These herbal medicines have been applied for many years in folk medicine, and extracts of these medicines have been used to study their pharmacological actions and mechanisms. Although effective and relatively safe, natural plant products have some side effects, such as hepatotoxicity and skin reactions effects of Piper methysticum. In addition, there are insufficient evidences to certify the safety of most traditional herbal medicine. In this review, we provide an overview of the current state of knowledge regarding a variety of natural plant products that are commonly used to treat insomnia to facilitate future studies.
    [Show full text]
  • Review Article Small Molecules from Nature Targeting G-Protein Coupled Cannabinoid Receptors: Potential Leads for Drug Discovery and Development
    Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2015, Article ID 238482, 26 pages http://dx.doi.org/10.1155/2015/238482 Review Article Small Molecules from Nature Targeting G-Protein Coupled Cannabinoid Receptors: Potential Leads for Drug Discovery and Development Charu Sharma,1 Bassem Sadek,2 Sameer N. Goyal,3 Satyesh Sinha,4 Mohammad Amjad Kamal,5,6 and Shreesh Ojha2 1 Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, Abu Dhabi, UAE 2Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, Abu Dhabi, UAE 3DepartmentofPharmacology,R.C.PatelInstituteofPharmaceuticalEducation&Research,Shirpur,Mahrastra425405,India 4Department of Internal Medicine, College of Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA 5King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia 6Enzymoics, 7 Peterlee Place, Hebersham, NSW 2770, Australia Correspondence should be addressed to Shreesh Ojha; [email protected] Received 24 April 2015; Accepted 24 August 2015 Academic Editor: Ki-Wan Oh Copyright © 2015 Charu Sharma et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The cannabinoid molecules are derived from Cannabis sativa plant which acts on the cannabinoid receptors types 1 and 2 (CB1 and CB2) which have been explored as potential therapeutic targets for drug discovery and development. Currently, there are 9 numerous cannabinoid based synthetic drugs used in clinical practice like the popular ones such as nabilone, dronabinol, and Δ - tetrahydrocannabinol mediates its action through CB1/CB2 receptors.
    [Show full text]
  • NRDC: Generally Recognized As Secret
    NRDC Report April 2014 Generally Recognized as Secret: Chemicals Added to Food in the United States Tom Neltner, J.D., Maricel Maffini, Ph.D. Natural Resources Defense Council In April 2014, the Natural Resources Defense Council (NRDC) released a report raising concerns about a loophole in the Food Additives Amendment of 1958 for substances designated by food manufacturers as “generally recognized as safe” (GRAS). The report identified 56 companies that appeared to market 275 chemicals for use in food based on undisclosed GRAS safety determinations. For each chemical we identified in this study, we did not find evidence that FDA had cleared them for use in food. The 1958 law exempted from the formal, extended FDA approval process common food ingredients like vinegar and vegetable oil whose use qualifies as GRAS. It may have appeared reasonable at the time, but that exemption has been stretched into a loophole that has swallowed the law. The exemption allows manufacturers to make safety determinations that the uses of their newest chemicals in food are safe without notifying the FDA. The agency’s attempts to limit these undisclosed GRAS determinations by asking industry to voluntarily inform the FDA about their chemicals are insufficient to ensure the safety of our food in today’s global marketplace with a complex food supply. Furthermore, no other developed country in the world has a system like GRAS to provide oversight of food ingredients. In Table 1 and 2 of the report, NRDC identified the 56 companies and the number of chemicals that each company appeared to market as GRAS without FDA clearance.
    [Show full text]
  • Herbal Remedies and Their Possible Effect on the Gabaergic System and Sleep
    nutrients Review Herbal Remedies and Their Possible Effect on the GABAergic System and Sleep Oliviero Bruni 1,* , Luigi Ferini-Strambi 2,3, Elena Giacomoni 4 and Paolo Pellegrino 4 1 Department of Developmental and Social Psychology, Sapienza University, 00185 Rome, Italy 2 Department of Neurology, Ospedale San Raffaele Turro, 20127 Milan, Italy; [email protected] 3 Sleep Disorders Center, Vita-Salute San Raffaele University, 20132 Milan, Italy 4 Department of Medical Affairs, Sanofi Consumer HealthCare, 20158 Milan, Italy; Elena.Giacomoni@sanofi.com (E.G.); Paolo.Pellegrino@sanofi.com (P.P.) * Correspondence: [email protected]; Tel.: +39-33-5607-8964; Fax: +39-06-3377-5941 Abstract: Sleep is an essential component of physical and emotional well-being, and lack, or dis- ruption, of sleep due to insomnia is a highly prevalent problem. The interest in complementary and alternative medicines for treating or preventing insomnia has increased recently. Centuries-old herbal treatments, popular for their safety and effectiveness, include valerian, passionflower, lemon balm, lavender, and Californian poppy. These herbal medicines have been shown to reduce sleep latency and increase subjective and objective measures of sleep quality. Research into their molecular components revealed that their sedative and sleep-promoting properties rely on interactions with various neurotransmitter systems in the brain. Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter that plays a major role in controlling different vigilance states. GABA receptors are the targets of many pharmacological treatments for insomnia, such as benzodiazepines. Here, we perform a systematic analysis of studies assessing the mechanisms of action of various herbal medicines on different subtypes of GABA receptors in the context of sleep control.
    [Show full text]
  • Therapeutic Applications of Compounds in the Magnolia Family
    Pharmacology & Therapeutics 130 (2011) 157–176 Contents lists available at ScienceDirect Pharmacology & Therapeutics journal homepage: www.elsevier.com/locate/pharmthera Associate Editor: I. Kimura Therapeutic applications of compounds in the Magnolia family Young-Jung Lee a, Yoot Mo Lee a,b, Chong-Kil Lee a, Jae Kyung Jung a, Sang Bae Han a, Jin Tae Hong a,⁎ a College of Pharmacy and Medical Research Center, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, Republic of Korea b Reviewer & Scientificofficer, Bioequivalence Evaluation Division, Drug Evaluation Department Pharmaceutical Safety Breau, Korea Food & Drug Administration, Republic of Korea article info abstract Keywords: The bark and/or seed cones of the Magnolia tree have been used in traditional herbal medicines in Korea, Magnolia China and Japan. Bioactive ingredients such as magnolol, honokiol, 4-O-methylhonokiol and obovatol have Magnolol received great attention, judging by the large number of investigators who have studied their Obovatol pharmacological effects for the treatment of various diseases. Recently, many investigators reported the Honokiol anti-cancer, anti-stress, anti-anxiety, anti-depressant, anti-oxidant, anti-inflammatory and hepatoprotective 4-O-methylhonokiol effects as well as toxicities and pharmacokinetics data, however, the mechanisms underlying these Cancer Nerve pharmacological activities are not clear. The aim of this study was to review a variety of experimental and Alzheimer disease clinical reports and, describe the effectiveness, toxicities and pharmacokinetics, and possible mechanisms of Cardiovascular disease Magnolia and/or its constituents. Inflammatory disease © 2011 Elsevier Inc. All rights reserved. Contents 1. Introduction .............................................. 157 2. Components of Magnolia ........................................ 159 3. Therapeutic applications in cancer ...................................
    [Show full text]
  • Synthesis of Magnolol and Its Analogue Compounds Synthese Von Magnolol Und Analog-Verbindungen Synthèse De Magnolol Et Ses Composés Analogues
    (19) TZZ ¥¥_Z_T (11) EP 2 539 310 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: C07C 37/055 (2006.01) C07C 37/62 (2006.01) 16.07.2014 Bulletin 2014/29 C07C 39/21 (2006.01) C07C 41/48 (2006.01) C07C 41/52 (2006.01) C07C 43/313 (2006.01) (2006.01) (2006.01) (21) Application number: 10705965.1 C07C 43/30 A61K 31/05 A61P 31/04 (2006.01) (22) Date of filing: 25.02.2010 (86) International application number: PCT/US2010/025378 (87) International publication number: WO 2011/106003 (01.09.2011 Gazette 2011/35) (54) SYNTHESIS OF MAGNOLOL AND ITS ANALOGUE COMPOUNDS SYNTHESE VON MAGNOLOL UND ANALOG-VERBINDUNGEN SYNTHÈSE DE MAGNOLOL ET SES COMPOSÉS ANALOGUES (84) Designated Contracting States: • SUBRAMANYAM, Ravi AT BE BG CH CY CZ DE DK EE ES FI FR GB GR Belle Mead HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL NJ 08502 (US) PT RO SE SI SK SM TR (74) Representative: Jenkins, Peter David (43) Date of publication of application: Page White & Farrer 02.01.2013 Bulletin 2013/01 Bedford House John Street (73) Proprietors: London WC1N 2BF (GB) •Colgate-Palmolive Company New York, NY 10022 (US) (56) References cited: • Indian Institute Of Chemical Technology US-A1- 2006 140 885 Andhra Pradesh (IN) • J. RUNEBERG: "Phenol Dehydrogenations" (72) Inventors: ACTA CHEMICA SCANDINAVICA, vol. 12, 1958, • REDDY, Basi, V., Subba pages 188-192, XP002575197 cited in the Nacharam (IN) application • YADAV, Jhillu, S.
    [Show full text]
  • Nutrition Biofiles7
    2007 Volume 2 Number 2 FOR LIFE SCIENCE RESEARCH DIETARY ANTIOXIDANTS OMEGA-3 FATTY ACIDS AND HEART DISEASE THE BIOACTIVE NUTRIENT EXPLORER METABOLITE LIBRARIES Examples of fruits and vegetables that contain antioxidants such as kaempferol, lycopene, and resveratrol. Nutrition Research sigma-aldrich.com Life Science Pathways Animated ATP Synthase & Glycolysis! The evolutionary pathway of life science research has brought today’s researchers full circle to a destination we now call metabolomics. n 1947, Sigma produced the first commercially The Enzyme Explorer’s Metabolic Pathways The Enzyme Explorer I available ATP. Since then, Sigma-Aldrich has Resource Center provides the online tools you need Assay Library consistently expanded its product portfolio to to explore the metabolome today. The largest collection of enzymatic maintain the most comprehensive line of organic • Metabolic Pathway Chart with 500 Hyperlinks assay procedures available online. More than 600 step-by-step metabolites, enzymes, and bio-analytical tools in to Product Listings, and Technical Data procedures for: the world. • Direct Access to 35 Nicholson Metabolic Mini-maps To strengthen our commitment to metabolic METABOLIC ENZYMES • Animated ATP Synthase Mechanism METABOLITE QUANTITATION education and research, Sigma-Aldrich is proud DIAGNOSTIC ENZYMES to announce the formation of a collaboration • Animated Glycolysis Pathway ANALYTICAL ENZYMES with the IUBMB to produce, animate, and • Isotopically Labeled Metabolites PROTEASES PROTEASE INHIBITORS publish the Nicholson Metabolic Pathway Charts. • Metabolite Libraries CELL SIGNALING ENZYMES PROTEIN QUANTITATION Visit the Assay Library at: sigma-aldrich.com/enzymeexplorer Visit us online today at: sigma-aldrich.com/metpath LEADERSHIP IN LIFE SCIENCE, HIGH TECHNOLOGY AND SERVICE sigma-aldrich.com SIGMA-ALDRICH CORPORATION • BOX 14508 • ST.
    [Show full text]
  • Honokiol and Magnolol As Renewable Resources for the Synthesis of Polymers Towards Biomedical and Engineering Applications
    HONOKIOL AND MAGNOLOL AS RENEWABLE RESOURCES FOR THE SYNTHESIS OF POLYMERS TOWARDS BIOMEDICAL AND ENGINEERING APPLICATIONS A Dissertation by KEVIN T. WACKER Submitted to the Office of Graduate and Professional Studies of Texas A&M University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Chair of Committee, Karen L. Wooley Committee Members, Lei Fang Jaime C. Grunlan David C. Powers Head of Department, Simon W. North May 2018 Major Subject: Chemistry Copyright 2018 Kevin T. Wacker ABSTRACT This dissertation has focused on the design, synthesis, and characterization of novel polymers derived from the renewable resources honokiol and magnolol. These natural products – isolated from magnolia officinalis – are highly functional and, thus, amenable to a broad range of synthetic organic transformations. The transformations explored in this work have yielded diverse monomers and, subsequently, polymer types which have included polycarbonates, thermosets, and olefin-based polymers that were studied for potential engineering or biomedical materials. A guiding theme in the development of polymers from honokiol and magnolol has been to control and vary the final polymer properties through the monomer design and polymerization chemistry. This work has used scalable syntheses, well-known chemistries, and, as the first examples of polymers synthesized from these natural products, it has laid the foundation to further explore material applications and new polymers based on honokiol and magnolol. Poly(honokiol carbonate) (PHC) was synthesized in one step from honokiol using step-growth polycondensation techniques. Synthetic conditions were screened to yield polymers of varying molecular weight and the resulting polymers were studied in their thermomechanical and biological properties.
    [Show full text]
  • Honokiol and Magnolol As Multifunctional Antioxidative Molecules for Dermatologic Disorders
    Molecules 2010, 15, 6452-6465; doi:10.3390/molecules15096452 OPEN ACCESS molecules ISSN 1420-3049 www.mdpi.com/journal/molecules Review Honokiol and Magnolol as Multifunctional Antioxidative Molecules for Dermatologic Disorders Jui-Lung Shen 1,2,3,#, Kee-Ming Man 2,4,5,#, Po-Hsun Huang 6, Wen-Chi Chen 4, Der-Cherng Chen 4, Ya-Wen Cheng 1, Po-Len Liu 7,*, Ming-Chih Chou 1,*, and Yung-Hsiang Chen 4,* 1 Institute of Medicine, Chung Shan Medical University, Taichung; Taiwan; E-Mails: [email protected] (J.L.S.); [email protected] (Y.W.C.) 2 Department of Anesthesiology, Tungs’ Taichung MetroHarbor Hospital, Taichung; Taiwan; E-Mail: [email protected] (K.M.M.) 3 Department of Dermatology, Taichung Veterans General Hospital, Taichung; Taiwan 4 Graduate Institute of Integrated Medicine, College of Chinese Medicine, Graduate Institute of Clinical Medical Science, Department of Urology, Department of Neurosurgery, China Medical University and Hospital, Taichung; Taiwan; E-Mails: [email protected] (W.C.C.); [email protected] (D.C.C.); [email protected] (Y.H.C.) 5 Graduate Institute of Geriatric Medicine, Anhui Medical University, Hefei; China 6 Division of Cardiology, Taipei Veterans General Hospital, Institute of Clinical Medicine, Cardiovascular Research Center, National Yang-Ming University, Taipei; Taiwan; E-Mail: [email protected] 7 Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung; Taiwan; E-Mail: [email protected] # Jui-Lung Shen and Kee-Ming Man contributed equally to this study. * Author to whom correspondence should be addressed; E-mail: [email protected] (P.L.); [email protected] (M.C.); [email protected] (Y.C.); Tel.: +886-4-22053366-3512; Fax: +886-4-2203-7690.
    [Show full text]
  • Phytochemicals Having Neuroprotective Properties from Dietary Sources and Medicinal Herbs
    PHCOG J REVIEW ARTICLE Phytochemicals Having Neuroprotective Properties from Dietary Sources and Medicinal Herbs G. Phani Kumar*, K.R. Anilakumar and S. Naveen Applied Nutrition Division, Defence Food Research Laboratory (DRDO), Ministry of Defence, India ABSTRACT Many neuropsychiatric and neurodegenerative disorders, such as Alzheimer's disease, anxiety, cerebrovascular impairment, depression, seizures, Parkinson's disease, etc. are predominantly appearing in the current era due to the stress full lifestyle. Treatment of these disorders with prolonged administration of synthetic drugs will lead to severe side effects. In the recent years, scientists have focused the attention of research towards phytochemicals to cure neurological disorders. Nootropic herb refers to the medicinal role of various plants/parts for their neuroprotective properties by the active phytochemicals including alkaloids, steroids, terpenoids, saponins, phenolics, flavonoids, etc. Phytocompounds from medicinal plants play a major part in maintaining the brain's chemical balance by acting upon the function of receptors for the major inhibitory neurotransmitters. Medicinal plants viz. Valeriana officinalis, Nardostachys jatamansi, Withania somnifera, Bacopa monniera, Ginkgo biloba and Panax ginseng have been used widely in a variety of traditional systems of therapy because of their adaptogenic, psychotropic and neuroprotective properties. This review highlights the importance of phytochemicals on neuroprotective function and other related disorders, in particular
    [Show full text]
  • Expression of Cyclooxygenase-2, Nitric Oxide Synthase 2
    in vivo 31 : 819-831 (2017) doi:10.21873/invivo.11135 Expression of Cyclooxygenase-2, Nitric Oxide Synthase 2 and Heme Oxygenase-1 mRNA Induced by Bis- Eugenol in RAW264.7 Cells and their Antioxidant Activity Determined Using the Induction Period Method YUKIO MURAKAMI, AKIFUMI KAWATA and SEIICHIRO FUJISAWA Division of Oral Diagnosis and General Dentistry, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Sakado, Japan Abstract. Background/Aim: To clarify the mechanisms induced the expression of HO-1 mRNA, and when combined responsible for the anti-inflammatory/proinflammatory with MMI it showed a potent antagonistic effect on BPO- activities of eugenol-related compounds, we investigated the induced antioxidant activity. The ability of methoxyphenols cytotoxicity and up-regulatory/down-refgulatory effects of the to inhibit LPS-stimulated Cox-2 gene expression declined in biphenols curcumin, bis-eugenol, magnolol and honokiol, the order curcumin >> isoeugenol > bis-eugenol >> and the monophenols eugenol and isoeugenol, on major eugenol, and the rank of ability was related to their ω value. regulators of cyclooxygenase-2 (Cox-2), nitric oxide synthase Conclusion: Most eugenol-related compounds had 2 (Nos2) and heme oxygenase-1 (HO-1) mRNA in RAW264.7 proinflammatory activity at high concentrations. However, cells. Materials and Methods: mRNA expression was they had also anti-inflammatory activity at lower investigated using real-time reverse transcriptase- concentrations. Eugenol-related compounds may exert polymerase chain reaction (RT-PCR), and the theoretical antioxidant and anti-inflammatory activity in LPS-stimulated parameters were calculated using the DFT/B3LYP/6-31* RAW264.7 cells possibly by inhibiting the activation of method.
    [Show full text]
  • 1H-Indole-3-Carboxylic Acid Is a Highly Selective Substrate for Glucuronidation by UGT1A1, Relative to B-Estradiol
    1521-009X/46/12/1836–1846$35.00 https://doi.org/10.1124/dmd.118.083709 DRUG METABOLISM AND DISPOSITION Drug Metab Dispos 46:1836–1846, December 2018 Copyright ª 2018 by The American Society for Pharmacology and Experimental Therapeutics 6-Chloro-5-[4-(1-Hydroxycyclobutyl)Phenyl]-1H-Indole-3-Carboxylic Acid is a Highly Selective Substrate for Glucuronidation by UGT1A1, Relative to b-Estradiol Kimberly Lapham, Jian Lin, Jonathan Novak, Christine Orozco, Mark Niosi, Li Di, Theunis C. Goosen, Sangwoo Ryu, Keith Riccardi, Heather Eng, Kimberly O. Cameron, and Amit S. Kalgutkar Medicine Design, Pfizer Inc., Groton, Connecticut (K.L., J.L., J.N., C.O., M.N., L.D., T.C.G., S.R., K.R., H.E.); and Medicine Design, Pfizer Inc., Cambridge, Massachusetts (K.O.C., A.S.K.) Received July 24, 2018; accepted September 5, 2018 Downloaded from ABSTRACT 6-Chloro-5-[4-(1-hydroxycyclobutyl)phenyl]-1H-indole-3-carboxylic of PF-06409577 to M1 by UGT1A1 occurred in a relatively selective acid (PF-06409577) is a direct activator of the human b1-containing fashion, compared with b-estradiol (ES), a conventional probe adenosine monophosphate-activated protein kinase (ΑMPK) isoforms. substrate of UGT1A1. The Michaelis-Menten constant (KM)and The clearance mechanism of PF-06409577 in animals and humans Vmax values describing the formation of M1 from PF-06409577 in involves uridine diphosphoglucuronosyl transferase (UGT)–mediated hrUGT1A1 and microsomal preparations from human intestine, dmd.aspetjournals.org glucuronidation to an acyl glucuronide metabolite of PF-06409577 liver, and kidney ranged from 131 to 212 mM(KM) and 107–3834 [(2S,3S,4S,5R,6S)-6-((6-chloro-5-(4-(1-hydroxycyclobutyl)phenyl)- pmol/min per milligram (Vmax) in the presence of 2% bovine serum 1H-indole-3-carbonyl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2- albumin.
    [Show full text]