DOCSLIB.ORG

(12) Patent Application Publication (10) Pub. No.: US 2007/0166255A1 GUPTA (43) Pub

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) Patent Application Publication (10) Pub. No.: US 2007/0166255A1 GUPTA (43) Pub US 20070166255A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2007/0166255A1 GUPTA (43) Pub. Date: Jul. 19, 2007 (54) TREATMENT OF TOPICAL DISCOMFORTS Continuation-in-part of application No. 10/904,665, INCLUDING ACNE, SUNBURN, DIAPER filed on Nov. 22, 2004. RASH, WOUND, WRINKLES AND DANDRUFF/HAIR LOSS BY NATURAL Publication Classification LGNANS VAFATTY ACID DESATURASE INHIBITION (51) Int. Cl. A6IR 8/49 (2006.01) A6IR 8/3 (2006.01) (76) Inventor: SHYAM K GUPTA, Scottsdale, AZ (52) U.S. Cl. ........................ 424/70.1; 514/473; 514/731; (US) 514/754 Correspondence Address: SHYAM. K. GUPTA BODERMI RESEARCH (57) ABSTRACT S221 E. WINDROSE DRIVE SCOTTSDALE, AZ 85254 (US) The present invention discloses compositions and method (21) Appl. No.: 11/670,942 ology based on certain natural lignans that provide treatment of topical discomforts and ailments including Sunburn, (22) Filed: Feb. 2, 2007 radiation burn, thermal burn and blisters, diaper rash, shav Related U.S. Application Data ing burn, wound, venous cannulation, acne, darkened skin pigmentation, skin wrinkles, dandruff, and hair loss; said (63) Continuation-in-part of application No. 1 1/161,856, treatment having achieved via topical inhibition of Fatty filed on Aug. 19, 2005. Acid Desaturases. CH3 Patent Application Publication Jul. 19, 2007 Sheet 1 of 4 US 2007/01662.55 A1 CH 2 HC ( ) ( ) CH 3 OH C OH HO O HO 4 O 2O HO O C OH 5 Figure 1. Lignan Structures Patent Application Publication Jul. 19, 2007 Sheet 2 of 4 US 2007/01662.55 A1 Lignan Silybin Werbascoside C CH p H O ps -d s-\ p 2 'rc \-d o CH Rosmarinic Acid Sesamine HO - -s -OH 1-CH3 -1N, --, -1^ -2 HCO -21s ^/ r r Y- OCH H CH O O Ove Tetrahydrocurcumin Cile OH Dihydroguaiaretic acid OCH H3CO CCH HCOs s 1Yoh Ho-sa CH Saucernetin NS Secoisolariciresinol Y1Y Yoch, CH4 HG CH3 OH HC CH3 - Me OMe MeO fat Y-k A 2'-OMs Mg Interiotherin Schisandrin 9 Me Figure 2. Examples of Lignans and Analogs Patent Application Publication Jul. 19, 2007 Sheet 3 of 4 US 2007/01662.55 A1 Patent Application Publication Jul. 19, 2007 Sheet 4 of 4 US 2007/01662.55 A1 OH OH DeSaturase Silybin O Dehydrosilybin Figure 4. Inhibition of Desaturase by Silybin US 2007/01662.55 A1 Jul. 19, 2007 TREATMENT OF TOPCAL DISCOMFORTS substituted cinnamic alcohols to a dibenzylbutane skeleton INCLUDING ACNE, SUNBURN, DIAPER RASH, 2. A neolignan is skeleton 3. When part of the human diet, WOUND, WRINKLES AND DANDRUFF/HAIR lignans are converted into the mammalian lignans known as LOSS BY NATURAL LIGNANS VAFATTY ACID enterodiol (4) and enterolactone (5) by intestinal bacteria. DESATURASE INHIBITION FIG. 1). 0001. This is a continuation-in-part of U.S. patent appli 0007 FIG. 1). cation Ser. No. 1 1/161,856: filed Aug. 19, 2005; the said application having disclosed certain furostanol Saponins and 0008 Alignan can be fused to another chemical struc Sapogenins that reduce sebum production. This is also a ture, for example, a flavone, or a saccharide. Biosynthesis of continuation-in-part of U.S. patent application Ser. No. lignans and lignins has been disclosed Lignin and Lignan 10/904,665; filed Nov. 22, 2004; the said application having Biosynthesis, Lewis et al. (ed), Am. Chem. Soc. Symposium disclosed a topical delivery system for cosmetic and phar (1998). Examples of various lignan structures of impor maceutical agents. tance to the present invention are shown in FIG. 2). 0002 The present invention discloses compositions and 0009 FIG. 2). methodology for topical application based on certain natural 0010 Natural lignans have been known for some time. lignans that provide treatment of topical discomforts and Lignans are phenolic-compounds widely distributed in ailments including Sunburn, radiation burn, thermal burn and plants. They can be found in different parts (roots, leafs, blisters, diaper rash, shaving burn, wound, Venous cannula stem, seeds, fruits) but mainly in Small amounts. In many tion, acne, darkened skin pigmentation, skin wrinkles, dan Sources (seeds, fruits), lignans are found as glycosidic druff, and hair loss, said treatment achieved via topical conjugates associated with fiber component of plants. The inhibition of Fatty Acid Desaturases. most common dietary sources of mammalian lignan precur sors are unrefined grain products. The highest concentra 0003 Topical discomfort relates to certain conditions that tions in edible plants have been found in flaxseed, followed can cause either physical pain and anxiety or mental (psy by unrefined grain products, particularly rye. Considerable chological) anguish. In most cases these are not life-threat amounts of lignans are also found in coniferous trees. The ening situations. The examples of Such physical pain and type of lignans differs in different species and the amounts anxiety include Sunburn, radiation burn, thermal burn and of lignans vary in different parts of the trees. The typical blisters, shaving burn, wound, Venous cannulation, and acne. lignans in heartwood of Norway spruce (Picea abies) are The examples mental or psychological anguish include hydroxymatairesinol (HMR), alpha-conidendrin, alpha dandruff, hair loss, skin wrinkles, and darkened skin pig conidendric acid, matairesinol, isolariciresinol, secoisolar mentation. iciresinol, liovil, picearesinol, lariciresinol and pinoresinol 0004 Fatty Acid Desaturases are enzymes that catalyze Ekman R: Distribution of lignans in Norway spruce, Acta the insertion of a double bond at the Delta position of fatty Academiae Aboensis, Ser B, 39:1–6 (1979). The far most acids. There seem to be two different families of fatty acid abundant single component of lignans in spruce is HMR, desaturases. The fatty acid desaturases of interest in the about 60 percent of total lignans, which occurs mainly in present invention are those belonging to family-2 of the unconjugated free form. Plant lignans Such as hydroxy desaturases, some of which are also called Delta-5-desatu matairesinol, matairesinol, lariciresinol and secoisolaricir rases and Delta-6-desaturases, or fatty acid desaturase-2. esinol, are converted by gut microflora to mammalian lig Fatty acid desaturases in skin have been unknown, until very nans, enterolactone or enterodiol. The mammalian lignans recently. The desaturases thus appear to work in a direction can also be manufactured synthetically M B Groen and J opposite to that of dehydrogenases, for example, 5-Alpha Leemhius, Tetrahedron Letters 21, 5043, (1980)). reductase, which causes the hydrogenation of the double 0011 Lignans are known to possess beneficial effects on bond in testosterone to form dihydrotestosterone (DHT), human health. The health benefits obtained with lignan rich which is biologically more active than testosterone. diet are, for example, decreased risk for various cancers and 0005 Deltaé-desaturase reaction, for example, is the cardiovascular diseases (Adlercreutz (1998) Phytoestrogens rate-limiting step in the conversion of linoleic acid and alpha and human health, In: Reproductive and Developmental linoleic acids to the longer, more highly unsaturated mem Toxicology (edited by Korach, K.). pp. 299-371, Marcel & bers of the n-6 and n-3 polyunsaturated fatty acids in the Dekker, NY.). metabolic pathway of mammalian cells. DeltaG-desaturase is 0012 Nam Mini Rev Med Chem., 8, 945 (2006) dis also required for the conversion of dietary linoleic acid to closed NF-kappaB inhibitor properties of lignans such as arachidonic acid. Delta6-desaturase has recently been shown to catalyze an unexpected 'sebaceous-type' reaction, that of manassantins, saucernetin, and saucerneol. converting palmitate into the mono-unsaturated fatty acid, 0013 Kubaneck et al. Phytochemistry, 54, 281 (2000) sapienate, a 16-carbon fatty acid with a single cis double report lignans with anti-feedant properties that includes bond at the sixth carbon from the carboxyl end. Sapienate is sauriol, licarin, dihydroguaiaretic acid, saucernetin, and sau the most abundant fatty acid in human sebum and among cerneol. hair-bearing animals is restricted to humans. 0014 Choong et al. British Journal of Pharmacology, 0006 Alignan is a chemical compound found in plants. 146, 752 (2005) report four lignans isolated from the bark These natural products are built up of C6C3 units (a pro of Machilus thunbergii (Lauraceae) that protected primary pylbenzene skeleton, 1), similar to terpenes, which are built cultures of rat cortical neurons from neurotoxicity induced on C5 (isoprene) units. Plant lignans are polyphenolic Sub by glutamate. Among the lignans, meso-dihydroguaiarectic stances derived from phenylalanine via dimerization of acid and licarin-A significantly attenuated glutamate-in US 2007/01662.55 A1 Jul. 19, 2007 duced neurotoxicity when added prior to or right after the 0029 Ahn et al. (KR20010036445) disclose a lignan excitotoxic glutamate challenge. compound having antioxidant activity to low density lipo protein and a process for separating the compound from 0015 Kassuya et al. Eur J. Pharmacol. 546, 182 (2006 Saururus chinensis Baill are provided, which can be effec report anti-inflammatory action of lignan Nirenthin isolated tively used for the prevention and treatment of a circulatory from Phyllanthus amarus. disease such as arteriosclerosis by oxidation of low density 0016 Yamauchi et al. Biosci Biotechnol Biochem, 70, lipoprotein. 1934 (2006 report radical and superoxide scavenging activ 0030 Parket al. (KR20010026440) disclose an ingestible ity of lignan Matairesinol and oxidized Matairesinol. composition for hangover
Load more

Recommended publications
  • Substances That Target Tumor Metabolism
    Biomedical Research 2011; 22 (2): 132-166 1181_On the metabolic origin of cancer: substances that target tumor metabolism. Maurice Israël 1 and Laurent Schwartz 2 1Biorebus 38 rue de Bassano 75008 Paris ; and 2 Av Aristide Briand 91440 Bures sur Yvette. France. 2LIX : Ecole Polytechnique Palaiseau France ; and Hôpital Pitié- Salpêtrière, service de radiothérapie, 75013 Paris. Abstract. Work from our group and others clearly suggest the key role of altered metabolism in cancer. The goal of this review is to summarize current knowledge on cancer metabolism, draw hy- pothesis explaining metabolic alterations and associated gene changes. Most importantly, we indicate a list of possible pharmacological targets. In short, tumor metabolism displays mixed glycolysis and neoglucogenesis features; most glycolitic enzymes are activate, but the pyruvate kinase and the pyruvate deshydrogenase are inhibited. This would result from an activation of their specific kinases, or from the inactivation of phosphatases, such as PP2A, regulated by me- thylation. In parallel, the phosphatase failure would enhance “tyrosine kinase receptor” signals, as occurs with oncogenes. Such signaling pathways are similar to those activated by insuline, or IGF- Growth hormone; they control mitosis, cell survival, carbohydrate metabolism. If for some reason, their regulation fails (oncogenes, PP2A methylation deficit, enhanced kinases…) a typical tumor metabolism starts the carcinogenic process. We also describe changes in the citric acid- urea cycles, polyamines, and show how body stores feed tumor metabolic pathways above and below “bottlenecks” resulting from wrongly switched enzymes. Studying the available lit- erature, we list a number of medications that target enzymes that are essential for tumor cells.
    [Show full text]
  • Natural Products As Alternative Choices for P-Glycoprotein (P-Gp) Inhibition
    Review Natural Products as Alternative Choices for P-Glycoprotein (P-gp) Inhibition Saikat Dewanjee 1,*, Tarun K. Dua 1, Niloy Bhattacharjee 1, Anup Das 2, Moumita Gangopadhyay 3, Ritu Khanra 1, Swarnalata Joardar 1, Muhammad Riaz 4, Vincenzo De Feo 5,* and Muhammad Zia-Ul-Haq 6,* 1 Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Raja S C Mullick Road, Kolkata 700032, India; [email protected] (T.K.D.); [email protected] (N.B.); [email protected] (R.K.); [email protected] (S.J.) 2 Department of Pharmaceutical Technology, ADAMAS University, Barasat, Kolkata 700126, India; [email protected] 3 Department of Bioechnology, ADAMAS University, Barasat, Kolkata 700126, India; [email protected] 4 Department of Pharmacy, Shaheed Benazir Bhutto University, Sheringal 18050, Pakistan; [email protected] 5 Department of Pharmacy, Salerno University, Fisciano 84084, Salerno, Italy 6 Environment Science Department, Lahore College for Women University, Jail Road, Lahore 54600, Pakistan * Correspondence: [email protected] (S.D.); [email protected] (V.D.F.); [email protected] (M.Z.-U.-H.) Academic Editor: Maria Emília de Sousa Received: 11 April 2017; Accepted: 15 May 2017; Published: 25 May 2017 Abstract: Multidrug resistance (MDR) is regarded as one of the bottlenecks of successful clinical treatment for numerous chemotherapeutic agents. Multiple key regulators are alleged to be responsible for MDR and making the treatment regimens ineffective. In this review, we discuss MDR in relation to P-glycoprotein (P-gp) and its down-regulation by natural bioactive molecules. P-gp, a unique ATP-dependent membrane transport protein, is one of those key regulators which are present in the lining of the colon, endothelial cells of the blood brain barrier (BBB), bile duct, adrenal gland, kidney tubules, small intestine, pancreatic ducts and in many other tissues like heart, lungs, spleen, skeletal muscles, etc.
    [Show full text]
  • Herbal Principles in Cosmetics Properties and Mechanisms of Action Traditional Herbal Medicines for Modern Times
    Traditional Herbal Medicines for Modern Times Herbal Principles in Cosmetics Properties and Mechanisms of Action Traditional Herbal Medicines for Modern Times Each volume in this series provides academia, health sciences, and the herbal medicines industry with in-depth coverage of the herbal remedies for infectious diseases, certain medical conditions, or the plant medicines of a particular country. Series Editor: Dr. Roland Hardman Volume 1 Shengmai San, edited by Kam-Ming Ko Volume 2 Rasayana: Ayurvedic Herbs for Rejuvenation and Longevity, by H.S. Puri Volume 3 Sho-Saiko-To: (Xiao-Chai-Hu-Tang) Scientific Evaluation and Clinical Applications, by Yukio Ogihara and Masaki Aburada Volume 4 Traditional Medicinal Plants and Malaria, edited by Merlin Willcox, Gerard Bodeker, and Philippe Rasoanaivo Volume 5 Juzen-taiho-to (Shi-Quan-Da-Bu-Tang): Scientific Evaluation and Clinical Applications, edited by Haruki Yamada and Ikuo Saiki Volume 6 Traditional Medicines for Modern Times: Antidiabetic Plants, edited by Amala Soumyanath Volume 7 Bupleurum Species: Scientific Evaluation and Clinical Applications, edited by Sheng-Li Pan Traditional Herbal Medicines for Modern Times Herbal Principles in Cosmetics Properties and Mechanisms of Action Bruno Burlando, Luisella Verotta, Laura Cornara, and Elisa Bottini-Massa Cover art design by Carlo Del Vecchio. CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2010 by Taylor and Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works Printed in the United States of America on acid-free paper 10 9 8 7 6 5 4 3 2 1 International Standard Book Number-13: 978-1-4398-1214-3 (Ebook-PDF) This book contains information obtained from authentic and highly regarded sources.
    [Show full text]
  • Multiple Myeloma Inhibitory Activity of Plant Natural Products
    cancers Review Multiple Myeloma Inhibitory Activity of Plant Natural Products Karin Jöhrer 1 and Serhat Sezai Ҫiҫek 2,* 1 Tyrolean Cancer Research Institute, Innrain 66, 6020 Innsbruck, Austria; karin.joehrer@tkfi.at 2 Department of Pharmaceutical Biology, Kiel University, Gutenbergstraße 76, 24118 Kiel, Germany * Correspondence: [email protected] Simple Summary: Multiple myeloma is the second most common hematological cancer and is still incurable. Although enhanced understanding of the disease background and the development of novel therapeutics during the last decade resulted in a significant increase of overall survival time, almost all patients relapse and finally succumb to their disease. Therefore, novel medications are urgently needed. Nature-derived compounds still account for the majority of new therapeutics and especially for the treatment of cancer often serve as lead compounds in drug development. The present review summarizes the data on plant natural products with in vitro and in vivo activity against multiple myeloma until the end of 2020, focusing on their structure–activity relationship as well as the investigated pathways and involved molecules. Abstract: A literature search on plant natural products with antimyeloma activity until the end of 2020 resulted in 92 compounds with effects on at least one human myeloma cell line. Compounds were divided in different compound classes and both their structure–activity-relationships as well as eventual correlations with the pathways described for Multiple Myeloma were discussed. Each of the major compound classes in this review (alkaloids, phenolics, terpenes) revealed interesting candidates, such as dioncophyllines, a group of naphtylisoquinoline alkaloids, which showed pronounced Citation: Jöhrer, K.; Ҫiҫek, S.S.
    [Show full text]
  • Dr. Duke's Phytochemical and Ethnobotanical Databases List of Chemicals for Chronic Venous Insufficiency/CVI
    Dr. Duke's Phytochemical and Ethnobotanical Databases List of Chemicals for Chronic Venous Insufficiency/CVI Chemical Activity Count (+)-AROMOLINE 1 (+)-CATECHIN 5 (+)-GALLOCATECHIN 1 (+)-HERNANDEZINE 1 (+)-PRAERUPTORUM-A 1 (+)-SYRINGARESINOL 1 (+)-SYRINGARESINOL-DI-O-BETA-D-GLUCOSIDE 1 (-)-ACETOXYCOLLININ 1 (-)-APOGLAZIOVINE 1 (-)-BISPARTHENOLIDINE 1 (-)-BORNYL-CAFFEATE 1 (-)-BORNYL-FERULATE 1 (-)-BORNYL-P-COUMARATE 1 (-)-CANADINE 1 (-)-EPICATECHIN 4 (-)-EPICATECHIN-3-O-GALLATE 1 (-)-EPIGALLOCATECHIN 1 (-)-EPIGALLOCATECHIN-3-O-GALLATE 2 (-)-EPIGALLOCATECHIN-GALLATE 3 (-)-HYDROXYJASMONIC-ACID 1 (-)-N-(1'-DEOXY-1'-D-FRUCTOPYRANOSYL)-S-ALLYL-L-CYSTEINE-SULFOXIDE 1 (1'S)-1'-ACETOXYCHAVICOL-ACETATE 1 (2R)-(12Z,15Z)-2-HYDROXY-4-OXOHENEICOSA-12,15-DIEN-1-YL-ACETATE 1 (7R,10R)-CAROTA-1,4-DIENALDEHYDE 1 (E)-4-(3',4'-DIMETHOXYPHENYL)-BUT-3-EN-OL 1 1,2,6-TRI-O-GALLOYL-BETA-D-GLUCOSE 1 1,7-BIS(3,4-DIHYDROXYPHENYL)HEPTA-4E,6E-DIEN-3-ONE 1 Chemical Activity Count 1,7-BIS(4-HYDROXY-3-METHOXYPHENYL)-1,6-HEPTADIEN-3,5-DIONE 1 1,8-CINEOLE 1 1-(METHYLSULFINYL)-PROPYL-METHYL-DISULFIDE 1 1-ETHYL-BETA-CARBOLINE 1 1-O-(2,3,4-TRIHYDROXY-3-METHYL)-BUTYL-6-O-FERULOYL-BETA-D-GLUCOPYRANOSIDE 1 10-ACETOXY-8-HYDROXY-9-ISOBUTYLOXY-6-METHOXYTHYMOL 1 10-GINGEROL 1 12-(4'-METHOXYPHENYL)-DAURICINE 1 12-METHOXYDIHYDROCOSTULONIDE 1 13',II8-BIAPIGENIN 1 13-HYDROXYLUPANINE 1 14-ACETOXYCEDROL 1 14-O-ACETYL-ACOVENIDOSE-C 1 16-HYDROXY-4,4,10,13-TETRAMETHYL-17-(4-METHYL-PENTYL)-HEXADECAHYDRO- 1 CYCLOPENTA[A]PHENANTHREN-3-ONE 2,3,7-TRIHYDROXY-5-(3,4-DIHYDROXY-E-STYRYL)-6,7,8,9-TETRAHYDRO-5H-
    [Show full text]
  • Metabolic Enzyme/Protease
    Inhibitors, Agonists, Screening Libraries www.MedChemExpress.com Metabolic Enzyme/Protease Metabolic pathways are enzyme-mediated biochemical reactions that lead to biosynthesis (anabolism) or breakdown (catabolism) of natural product small molecules within a cell or tissue. In each pathway, enzymes catalyze the conversion of substrates into structurally similar products. Metabolic processes typically transform small molecules, but also include macromolecular processes such as DNA repair and replication, and protein synthesis and degradation. Metabolism maintains the living state of the cells and the organism. Proteases are used throughout an organism for various metabolic processes. Proteases control a great variety of physiological processes that are critical for life, including the immune response, cell cycle, cell death, wound healing, food digestion, and protein and organelle recycling. On the basis of the type of the key amino acid in the active site of the protease and the mechanism of peptide bond cleavage, proteases can be classified into six groups: cysteine, serine, threonine, glutamic acid, aspartate proteases, as well as matrix metalloproteases. Proteases can not only activate proteins such as cytokines, or inactivate them such as numerous repair proteins during apoptosis, but also expose cryptic sites, such as occurs with β-secretase during amyloid precursor protein processing, shed various transmembrane proteins such as occurs with metalloproteases and cysteine proteases, or convert receptor agonists into antagonists and vice versa such as chemokine conversions carried out by metalloproteases, dipeptidyl peptidase IV and some cathepsins. In addition to the catalytic domains, a great number of proteases contain numerous additional domains or modules that substantially increase the complexity of their functions.
    [Show full text]
  • Overview of the Anti-Inflammatory Effects, Pharmacokinetic Properties
    Acta Pharmacologica Sinica (2018) 39: 787–801 © 2018 CPS and SIMM All rights reserved 1671-4083/18 www.nature.com/aps Review Article Overview of the anti-inflammatory effects, pharmacokinetic properties and clinical efficacies of arctigenin and arctiin from Arctium lappa L Qiong GAO, Mengbi YANG, Zhong ZUO* School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China Abstract Arctigenin (AR) and its glycoside, arctiin, are two major active ingredients of Arctium lappa L (A lappa), a popular medicinal herb and health supplement frequently used in Asia. In the past several decades, bioactive components from A lappa have attracted the attention of researchers due to their promising therapeutic effects. In the current article, we aimed to provide an overview of the pharmacology of AR and arctiin, focusing on their anti-inflammatory effects, pharmacokinetics properties and clinical efficacies. Compared to acrtiin, AR was reported as the most potent bioactive component of A lappa in the majority of studies. AR exhibits potent anti-inflammatory activities by inhibiting inducible nitric oxide synthase (iNOS) via modulation of several cytokines. Due to its potent anti-inflammatory effects, AR may serve as a potential therapeutic compound against both acute inflammation and various chronic diseases. However, pharmacokinetic studies demonstrated the extensive glucuronidation and hydrolysis of AR in liver, intestine and plasma, which might hinder its in vivo and clinical efficacy after oral administration. Based on the reviewed pharmacological and pharmacokinetic characteristics of AR, further pharmacokinetic and pharmacodynamic studies of AR via alternative administration routes are suggested to promote its ability to serve as a therapeutic agent as well as an ideal bioactive marker for A lappa.
    [Show full text]
  • Investigation of the Antidiabetic Activity Of
    INVESTIGATION OF THE ANTIDIABETIC ACTIVITY OF CNICUS BENEDICTUS L. IN RATS. RAYMONDE BAMBOUKOU BEKALE (B. Pharm, UWC) A thesis submitted in partial fulfilment of the requirements for the degree of Magister Pharmaceuticae in the School of Pharmacy, University of the Western Cape SUPERVISOR: PROFESSOR GEORGE J. AMABEOKU NOVEMBER 2016 i DECLARATION I declare that the thesis, Investigation of the antidiabetic activity of Cnicusbenedictus L. in rats, is my own work, that it has not been submitted before for any degree examination in any other University and that all the sources I have used or quoted have been indicated and acknowledged by complete reference. Raymonde BAMBOUKOU BEKALE November 2016 Signed……………………………….. ii DEDICATION I dedicate this thesis to my loving mother, Boubwetata Loba Helene and my family for their sacrifices and endless love, care and encouragement that has got me to where I am today. Thank you for believing in me and supporting me to be the best. iii ACKNOWLEDGEMENTS First of all, I thank the Almighty God, our Saviour, for His Mercy, Guidance and Protection throughout the years. The completion of this work has come as a product of hard work and I would like to express my sincere gratitude to the following individual and organizations, whose involvement in my life enabled me to complete this thesis: My supervisor, PROFESSOR GEORGE J. AMABEOKU for his commitment, guidance, patience, support, advice and valuable contributions made towards my study. I am privileged to have worked alongside him. The National Research Foundation for financial support. Mrs Eloise for her assistance with laboratory technicalities. MrsVirginaMvula for the maintenance of the animal house and upkeep of the animals.
    [Show full text]
  • Plant. Biotechnol. 30(2)
    Plant Biotechnology 30, 97–109 (2013) DOI: 10.5511/plantbiotechnology.12.1230a Original Paper A lignan O-methyltransferase catalyzing the regioselective methylation of matairesinol in Carthamus tinctorius Toshiaki Umezawa1,2,*,†, Safendrri Komara Ragamustari1,2,†, Tomoyuki Nakatsubo1, Shohei Wada1, Laigeng Li3,4, Masaomi Yamamura1, Norikazu Sakakibara1,5, Takefumi Hattori1,6, Shiro Suzuki1, Vincent L. Chiang3 1 Research Institute for Sustainable Humanosphere, Kyoto University, Uji, Kyoto 611-0011, Japan; 2 Institute of Sustainability Science, Kyoto University, Uji, Kyoto 611-0011, Japan; 3 Department of Forestry and Environmental Resources, College of Natural Resources, North Carolina State University, Raleigh, NC 27695-7247, USA; 4 Institute of Plant Physiology and Ecology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China; 5 Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, Sanuki, Kagawa 769-2193, Japan; 6 Institute of Socio-Arts and Sciences, The University of Tokushima, Tokushima 770-8502, Japan * E-mail: [email protected] Tel: +81-774-38-3625 Fax: +81-774-38-3682 Received December 14, 2012; accepted December 30, 2012 (Edited by T. Aoki) Abstract Lignans are a group of plant phenolic compounds with various biological activities, including antitumor and antioxidant properties. O-Methylation is a critical step in biosynthesis of these compounds. However, little is known about the O-methyltransferase (OMT) enzymes that catalyze lignan O-methylation. We discovered a highly regioselective OMT activity in safflower (Carthamus tinctorius) seeds that catalyzed the methylation of matairesinol, a dibenzylbutyrolactone lignan, into 4′-O-methylmatairesinol (arctigenin) but not 4-O-methylmatairesinol (isoarctigenin). By examining such OMT activity in correlation with OMT transcript abundances during seed development, we cloned a few putative OMT cDNAs and produced their recombinant proteins in Escherichia coli.
    [Show full text]
  • Potential Neuroprotective Effects of Adiponectin in Alzheimer's Disease
    International Journal of Molecular Sciences Review Potential Neuroprotective Effects of Adiponectin in Alzheimer’s Disease Roy Chun-Laam NG 1,2 and Koon-Ho CHAN 1,2,3,4,* 1 Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; [email protected] 2 Research Center of Heart, Brain, Hormone and Healthy Aging, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China 3 Hong Kong University Alzheimer’s Disease Research Network, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China 4 Neuroimmunology and Neuroinflammation Research Laboratory, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China * Correspondence: [email protected]; Tel.: +852-3917-9735 Academic Editor: Katalin Prokai-Tatrai Received: 23 December 2016; Accepted: 28 February 2017; Published: 9 March 2017 Abstract: The adipocyte-secreted protein adiponectin (APN) has several protective functions in the peripheral tissues including insulin sensitizing, anti-inflammatory and anti-oxidative effects that may benefit neurodegenerative diseases such as Alzheimer’s disease (AD). In addition, dysregulation of cerebral insulin sensitivities and signaling activities have been implicated in AD. Emerging insights into the mechanistic roles of adiponectin and AD highlight the potential therapeutic effects for AD through insulin signaling. Keywords: adiponectin; Alzheimer’s disease; cognitive impairments; Amyloid-β 1. Introduction The central nervous system (CNS) is separated from the peripheral circulations by the blood-brain barrier (BBB), which stringently controls substance penetration in order to protect the brain from pathogenic micro-organisms and harmful toxins. The CNS receives and integrates information to coordinate the whole body’s activities.
    [Show full text]
  • Association of Adipose Tissue and Adipokines with Development of Obesity-Induced Liver Cancer
    International Journal of Molecular Sciences Review Association of Adipose Tissue and Adipokines with Development of Obesity-Induced Liver Cancer Yetirajam Rajesh 1 and Devanand Sarkar 2,* 1 Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298, USA; [email protected] 2 Massey Cancer Center, Department of Human and Molecular Genetics, VCU Institute of Molecular Medicine (VIMM), Virginia Commonwealth University, Richmond, VA 23298, USA * Correspondence: [email protected]; Tel.: +1-804-827-2339 Abstract: Obesity is rapidly dispersing all around the world and is closely associated with a high risk of metabolic diseases such as insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease (NAFLD), leading to carcinogenesis, especially hepatocellular carcinoma (HCC). It results from an imbalance between food intake and energy expenditure, leading to an excessive accumulation of adipose tissue (AT). Adipocytes play a substantial role in the tumor microenvironment through the secretion of several adipokines, affecting cancer progression, metastasis, and chemoresistance via diverse signaling pathways. AT is considered an endocrine organ owing to its ability to secrete adipokines, such as leptin, adiponectin, resistin, and a plethora of inflammatory cytokines, which modulate insulin sensitivity and trigger chronic low-grade inflammation in different organs. Even though the precise mechanisms are still unfolding, it is now established that the dysregulated secretion of adipokines by AT contributes to the development of obesity-related metabolic disorders. This review focuses on several obesity-associated adipokines and their impact on obesity-related Citation: Rajesh, Y.; Sarkar, D. metabolic diseases, subsequent metabolic complications, and progression to HCC, as well as their Association of Adipose Tissue and role as potential therapeutic targets.
    [Show full text]
  • Botanical Medicine
    prohealth QUICK REFERENCE EVIDENCE INFORMED BOTANICAL MEDICINE ,ĞƌďƐ͕ŶƵƚƌŝƟŽŶ͕ŚŽƌŵŽŶĞƐΘŵĞĚŝĐĂƟŽŶƐ ƌ͘DĂƌŝƐĂDĂƌĐŝĂŶŽΘƌ͘EŝŬŝƚĂ͘sŝnjŶŝĂŬ Introduction ............... 1 Botanical Studying Tips ................. iii Plant Harvesting ............................ vi Intro Intro Food is Medicine ........7 3URWHLQIDW¿EHUFDUERK\GUDWHV .... 9 A Vitamins & minerals .......................14 B Actions ....................... 31 C Constituents............... 59 D Pharmacy ................... 73 E Monographs A-Z.... ..... 85 F Appendix .................... 370 G Toxicology, CIs & Safe Dosing .............370 +HUEVLQ3UHJQDQF\ ............................. 376 H +HUEVLQ3HGLDWULFV .............................. 377 I 13/(; ERDUGH[DPKHUEOLVW ............ 378 +HUEVE\)DPLO\ ................................... 379 J +HUE'UXJ1XWULHQW,QWHUDFWLRQV .......... 382 K Medications (drug & use) .....................386 L Index .......................... 403 +HUEVE\ODWLQQDPH ............................. 406 M +HUEVE\FRPPRQQDPH ..................... 407 N Congratulations RQPDNLQJWKHEHVWLQYHVWPHQWRI\RXUOLIH\RXURZQHGXFDWLRQDQG\RXU O FRQWLQXHGVHUYLFHWR\RXUSDWLHQW¶VTXDOLW\RIOLIH7RKHOSVXSSRUW\RXWKLVWH[WZDVFUHDWHG P DVWKHPRVWXSWRGDWHIXQFWLRQDODQGFRVWHIIHFWLYHFOLQLFDOWH[WDYDLODEOH&RXQWOHVVKRXUVRI UHVHDUFK GHVLJQZHUHVSHQWWRGHYHORSWKHFRQWHQW IRUPDW,QIRUPDWLRQVRXUFHVLQFOXGH Q KXQGUHGVRIRULJLQDOSHHUUHYLHZHGUHVHDUFKDUWLFOHVZLWKFXWWLQJHGJHLQIRUPDWLRQ GHFDGHVRI R HYLGHQFHLQIRUPHGEHVWSUDFWLFHV PXOWLGLVFLSOLQDU\FOLQLFDOH[SHULHQFHZLWKDIRFXVRQresults S based medicine. ,QRUGHUWRJHWWKHPRVWFOLQLFDOXWLOLW\IURPWKLVWH[WLWPXVWEHDYDLODEOHDWDOOWLPHVDVVXFK
    [Show full text]