Determination of the Total Dietary Polyphenol Load of a Population of Healthy Adults In
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Raman Imaging of Small Biomolecules
BB48CH15_Min ARjats.cls April 16, 2019 13:8 Annual Review of Biophysics Raman Imaging of Small Biomolecules Yihui Shen, Fanghao Hu, and Wei Min Department of Chemistry, Columbia University, New York, NY 10027, USA; email: [email protected] Annu. Rev. Biophys. 2019. 48:347–69 Keywords First published as a Review in Advance on Raman microscopy, small molecule imaging, vibrational tags, lipid March 20, 2019 metabolism, drug imaging The Annual Review of Biophysics is online at biophys.annualreviews.org Abstract Access provided by Columbia University on 06/21/19. For personal use only. https://doi.org/10.1146/annurev-biophys-052118- Imaging techniques greatly facilitate the comprehensive knowledge of Annu. Rev. Biophys. 2019.48:347-369. Downloaded from www.annualreviews.org 115500 biological systems. Although imaging methodology for biomacromolecules Copyright © 2019 by Annual Reviews. such as protein and nucleic acids has been long established, micro- All rights reserved scopic techniques and contrast mechanisms are relatively limited for small biomolecules, which are equally important participants in biological pro- cesses. Recent developments in Raman imaging, including both microscopy and tailored vibrational tags, have created exciting opportunities for non- invasive imaging of small biomolecules in living cells, tissues, and organ- isms. Here, we summarize the principle and workflow of small-biomolecule imaging by Raman microscopy. Then, we review recent efforts in imaging, for example, lipids, metabolites, and drugs. The unique advantage of Raman imaging has been manifested in a variety of applications that have provided novel biological insights. 347 BB48CH15_Min ARjats.cls April 16, 2019 13:8 Contents THENEEDFORIMAGINGSMALLBIOMOLECULES........................ 348 IMAGINGSMALLMOLECULESBYVIBRATIONALCONTRAST............. 349 LINEAR AND NONLINEAR RAMAN SCATTERING SPECTROSCOPY ANDMICROSCOPY......................................................... -
Small Molecules, Big Impact
FOR RESEARCH USE ONLY. NOT INTENDED FOR HUMAN OR ANIMAL DIAGNOSTIC OR THERAPEUTIC USES. STEMCELL TECHNOLOGIES INC.’S QUALITY MANAGEMENT SYSTEM IS CERTIFIED TO ISO 13485 MEDICAL DEVICE STANDARDS. TGFβ: The TGFβ superfamily members are major regulators of self-renewal and differentiation to mesendodermal lineages. p38 / p53: p38 MAPK is activated in response to cellular stresses, and influences apoptosis and cellular differentiation. p53 is activated in Pathway Activators: IDE1, IDE2; Pathway Inhibitors: SB431542, LY364947, RepSox, Dorsomorphin, LDN193189 response to cellular stresses and regulates growth arrest, apoptosis and/or DNA repair. Inhibition of p53 is used to facilitate reprogramming. Pathway Inhibitors: BIRB-796, SB202190, SB203580, Cyclic Pifithrin-α, Pifithrin-μ Hedgehog: The Hedgehog pathway is important in the differentiation of mesenchymal subtypes (e.g. osteocytes) and in neural subtypes (e.g. dopaminergic neurons). FGF: FGF signaling via MEK/ERK is critical for self-renewal and proliferation of human PSCs. However, other receptor tyrosine kinases can Pathway Activator: Purmorphamine; Pathway Inhibitors: Cyclopamine, HPI-1 also act through the MEK/ERK and PI3K signaling pathways. Pathway Activators: Pyrintegrin, PS-48; Pathway Inhbitors: Pluripotin, PD0325901, PD98059, Reversine IWP-2 WNT: The WNT pathway regulates differentiation to the mesoendodermal lineages, induces self-renewal of PSCs, and aids in reprogramming. IWP-3 Pathway Activators: BIO, CHIR99021, Kenpaullone, SB216763; Pathway Inhibitors: IWP-2, IWP-3, IWP-4, -
Plant Phenolics: Bioavailability As a Key Determinant of Their Potential Health-Promoting Applications
antioxidants Review Plant Phenolics: Bioavailability as a Key Determinant of Their Potential Health-Promoting Applications Patricia Cosme , Ana B. Rodríguez, Javier Espino * and María Garrido * Neuroimmunophysiology and Chrononutrition Research Group, Department of Physiology, Faculty of Science, University of Extremadura, 06006 Badajoz, Spain; [email protected] (P.C.); [email protected] (A.B.R.) * Correspondence: [email protected] (J.E.); [email protected] (M.G.); Tel.: +34-92-428-9796 (J.E. & M.G.) Received: 22 October 2020; Accepted: 7 December 2020; Published: 12 December 2020 Abstract: Phenolic compounds are secondary metabolites widely spread throughout the plant kingdom that can be categorized as flavonoids and non-flavonoids. Interest in phenolic compounds has dramatically increased during the last decade due to their biological effects and promising therapeutic applications. In this review, we discuss the importance of phenolic compounds’ bioavailability to accomplish their physiological functions, and highlight main factors affecting such parameter throughout metabolism of phenolics, from absorption to excretion. Besides, we give an updated overview of the health benefits of phenolic compounds, which are mainly linked to both their direct (e.g., free-radical scavenging ability) and indirect (e.g., by stimulating activity of antioxidant enzymes) antioxidant properties. Such antioxidant actions reportedly help them to prevent chronic and oxidative stress-related disorders such as cancer, cardiovascular and neurodegenerative diseases, among others. Last, we comment on development of cutting-edge delivery systems intended to improve bioavailability and enhance stability of phenolic compounds in the human body. Keywords: antioxidant activity; bioavailability; flavonoids; health benefits; phenolic compounds 1. Introduction Phenolic compounds are secondary metabolites widely spread throughout the plant kingdom with around 8000 different phenolic structures [1]. -
Phase I and Ii Enzyme Induction and Inhibition by Secoisolariciresinol Diglucoside and Its Aglycone
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by University of Saskatchewan's Research Archive PHASE I AND II ENZYME INDUCTION AND INHIBITION BY SECOISOLARICIRESINOL DIGLUCOSIDE AND ITS AGLYCONE A Thesis Submitted to the College of Graduate Studies and Research in Partial Fulfillment of the Requirements for the Degree of Master of Science in the Toxicology Graduate Program University of Saskatchewan Saskatoon, Saskatchewan Canada Erin Margaret Rose Boyd ©Copyright Erin Margaret Rose Boyd, April 2007, All rights reserved. PERMISSION TO USE In presenting this thesis in partial fulfillment of the requirements for a Postgraduate degree from the University of Saskatchewan, I agree that the Libraries of this University may make it freely available for inspection. I further agree that permission for copying of this thesis in any manner, in whole or in part, for scholarly purposes may be granted by the professor or professors who supervised my thesis work or, in their absence, by the Head of the Department or the Dean of the College in which my thesis work was done. It is also understood that any copying or publication or use of this thesis or parts thereof for financial gain shall not be allowed without my written permission. It is also understood that due recognition shall be given to me and to the University of Saskatchewan in any scholarly use which may be made of any material in my thesis. Requests for permission to copy or to make other use of material in this thesis in whole or part should be addressed to: Chair of the Toxicology Graduate Program Toxicology Centre University of Saskatchewan 44 Campus Drive Saskatoon, SK, Canada, S7N 5B3 i ABSTRACT The flaxseed lignan, secoisolariciresinol diglucoside (SDG), and its aglycone, secoisolariciresinol (SECO), have demonstrated benefits in the treatment and/or prevention of cancer, diabetes and cardiovascular disease. -
Monoclonal Antibodies and Small-Molecule Drugs: WHAT GENERAL NEUROLOGISTS NEED to KNOW
THIS CONTENT IS SPONSORED BY AMGEN INC. AND NOVARTIS PHARMACEUTICALS CORPORATION USA-334-83498 Monoclonal Antibodies and Small-Molecule Drugs: WHAT GENERAL NEUROLOGISTS NEED TO KNOW APRIL 2020 I VOL. 28 NO. 4 A Member of the Network Introduction plasma concentration 1–8 days) than IV, but this route permits self- Numerous drug modalities have been approved to treat neurologic administration at home.9,22 diseases, including small-molecule drugs (SMDs) and biologics SMDs generally have wide distribution into tissues, organs and such as monoclonal antibodies (mAbs).1-3 While both are consid- plasma.10,23 They are metabolized by CYP450 enzymes via oxidation, ered targeted therapies,2-7 each has unique characteristics that may leading to renal elimination in the urine, and by conjugation reac- affect their use in clinical practice.5,8,9 This article describes the gen- tions (eg, glucuronidation), leading to hepatic/biliary elimination in eral characteristics of SMDs and mAbs and discusses some of their the stool.10,24,25 mAbs have a small range of distribution.10,23 Particu- safety implications relevant to their use by general neurologists in larly relevant to neurology, therapeutic mAbs do not readily cross clinical practice. the blood–brain barrier and therefore have minimal distribution in the central nervous system (CNS).8,9 Therapeutic mAbs are also Characteristics of SMDs and mAbs too large for clearance by renal or hepatic mechanisms, and instead The general characteristics and pharmacokinetics (PK) of are metabolized by two primary -
Differential Anticancer Activity of Pterostilbene Against Three
ANTICANCER RESEARCH 37 : 6153-6159 (2017) doi:10.21873/anticanres.12064 Differential Anticancer Activity of Pterostilbene Against Three Subtypes of Human Breast Cancer Cells REI WAKIMOTO, MISAKI ONO, MIKAKO TAKESHIMA, TAKAKO HIGUCHI and SHUJI NAKANO Graduate School of Health and Nutritional Sciences, Nakamura Gakuen University, Fukuoka, Japan Abstract. Although pterostilbene, a natural analog of factor receptor 2 (HER2) expression. Therapeutic options for resveratrol, has potent antitumor activity against several patients with advanced breast cancer are limited and depend human cancer types, the possible inhibitory mechanisms on the breast cancer subtype. Although survival of patients against subtypes of human breast cancer with different with breast cancer has been improved by hormonal and hormone receptor and human epidermal growth factor receptor targeted therapy in recent years, triple-negative breast cancer, 2 (HER2) status remain unknown. We investigated the which is clinically negative for expression of ER, PR and anticancer activity of pterostilbene using three subtypes of HER2, is associated with a poor prognosis (2). Because there breast cancer cell lines. Pterostilbene treatment exhibited a are a limited number of treatments for triple-negative breast dose-dependent antiproliferative activity, with the greatest cancer, development of novel treatment options and prevention growth inhibition observed in triple-negative MDA-MB-468 for this type of breast cancer is extremely important. In this cells. Although pterostilbene arrested cell-cycle progression at context, fruit and vegetables have attracted attention because the G 0/G 1 phase regardless of breast cancer subtype, its their intake has been shown to reduce the risk of breast cancer apoptosis-inducing activity was highly apparent in MDA-MB- (3), and differentially affect ER-negative and -positive breast 468 cells. -
Modulation of Lipid Metabolism by Phytosterol Stearates and Black Raspberry Seed Oils
University of Nebraska - Lincoln DigitalCommons@University of Nebraska - Lincoln Nutrition & Health Sciences Dissertations & Theses Nutrition and Health Sciences, Department of 5-2010 Modulation of Lipid Metabolism by Phytosterol Stearates and Black Raspberry Seed Oils Mark McKinley Ash University of Nebraska at Lincoln, [email protected] Follow this and additional works at: https://digitalcommons.unl.edu/nutritiondiss Part of the Dietetics and Clinical Nutrition Commons, and the Molecular, Genetic, and Biochemical Nutrition Commons Ash, Mark McKinley, "Modulation of Lipid Metabolism by Phytosterol Stearates and Black Raspberry Seed Oils" (2010). Nutrition & Health Sciences Dissertations & Theses. 17. https://digitalcommons.unl.edu/nutritiondiss/17 This Article is brought to you for free and open access by the Nutrition and Health Sciences, Department of at DigitalCommons@University of Nebraska - Lincoln. It has been accepted for inclusion in Nutrition & Health Sciences Dissertations & Theses by an authorized administrator of DigitalCommons@University of Nebraska - Lincoln. Modulation of Lipid Metabolism by Phytosterol Stearates and Black Raspberry Seed Oils by Mark McKinley Ash A THESIS Presented to the Faculty of The Graduate College at the University of Nebraska In Partial Fulfillment of Requirements For the Degree of Master of Science Major: Nutrition Under the Supervision of Professor Timothy P. Carr Lincoln, Nebraska May, 2010 Modulation of Lipid Metabolism by Phytosterol Stearates and Black Raspberry Seed Oils Mark McKinley Ash, M.S. University of Nebraska, 2010 Adviser: Timothy P. Carr Naturally occurring compounds and lifestyle modifications as combination and mono- therapy are increasingly used for dyslipidemia. Specficially, phytosterols and fatty acids have demonstrated an ability to modulate cholesterol and triglyceride metabolism in different fashions. -
Phenolics in Human Health
International Journal of Chemical Engineering and Applications, Vol. 5, No. 5, October 2014 Phenolics in Human Health T. Ozcan, A. Akpinar-Bayizit, L. Yilmaz-Ersan, and B. Delikanli with proteins. The high antioxidant capacity makes Abstract—Recent research focuses on health benefits of polyphenols as an important key factor which is involved in phytochemicals, especially antioxidant and antimicrobial the chemical defense of plants against pathogens and properties of phenolic compounds, which is known to exert predators and in plant-plant interferences [9]. preventive activity against infectious and degenerative diseases, inflammation and allergies via antioxidant, antimicrobial and proteins/enzymes neutralization/modulation mechanisms. Phenolic compounds are reactive metabolites in a wide range of plant-derived foods and mainly divided in four groups: phenolic acids, flavonoids, stilbenes and tannins. They work as terminators of free radicals and chelators of metal ions that are capable of catalyzing lipid oxidation. Therefore, this review examines the functional properties of phenolics. Index Terms—Health, functional, phenolic compounds. I. INTRODUCTION In recent years, fruits and vegetables receive considerable interest depending on type, number, and mode of action of the different components, so called as “phytochemicals”, for their presumed role in the prevention of various chronic diseases including cancers and cardiovascular diseases. Plants are rich sources of functional dietary micronutrients, fibers and phytochemicals, such -
Mechanisms of Action for Small Molecules Revealed by Structural Biology in Drug Discovery
International Journal of Molecular Sciences Review Mechanisms of Action for Small Molecules Revealed by Structural Biology in Drug Discovery Qingxin Li 1,* and CongBao Kang 2,* 1 Guangdong Provincial Engineering Laboratory of Biomass High Value Utilization, Guangdong Provincial Bioengineering Institute (Guangzhou Sugarcane Industry Research Institute), Guangdong Academy of Sciences, Guangzhou 510316, China 2 Experimental Drug Development Centre (EDDC), Agency for Science, Technology and Research (A*STAR), 10 Biopolis Road, Chromos, #05-01, Singapore 138670, Singapore * Correspondence: [email protected] (Q.L.); [email protected] (C.K.); Tel.: +86-020-84168436 (Q.L.); +65-64070602 (C.K.) Received: 12 June 2020; Accepted: 20 July 2020; Published: 24 July 2020 Abstract: Small-molecule drugs are organic compounds affecting molecular pathways by targeting important proteins. These compounds have a low molecular weight, making them penetrate cells easily. Small-molecule drugs can be developed from leads derived from rational drug design or isolated from natural resources. A target-based drug discovery project usually includes target identification, target validation, hit identification, hit to lead and lead optimization. Understanding molecular interactions between small molecules and their targets is critical in drug discovery. Although many biophysical and biochemical methods are able to elucidate molecular interactions of small molecules with their targets, structural biology is the most powerful tool to determine the mechanisms of action for both targets and the developed compounds. Herein, we reviewed the application of structural biology to investigate binding modes of orthosteric and allosteric inhibitors. It is exemplified that structural biology provides a clear view of the binding modes of protease inhibitors and phosphatase inhibitors. -
Comparison of Antioxidant Activities and Total Polyphenolic and Methylxanthine Contents Between the Unripe Fruit and Leaves of Ilex Paraguariensis A
ORIGINAL ARTICLES Universidade Regional Integrada do Alto Uruguai e das Misso˜es1, Programa de Po´s-Graduac¸a˜o em Cieˆncias Farmaceˆuti- cas2, Curso de Farma´cia3, Departamento de Microbiologia4, Departamento de Farma´cia Industrial5, Universidade Federal de Santa Maria, Campus Camobi, Santa Maria, Rio Grande do Sul, Brasil Comparison of antioxidant activities and total polyphenolic and methylxanthine contents between the unripe fruit and leaves of Ilex paraguariensis A. St. Hil. A. Schubert1, D. F. Pereira2, F. F. Zanin3, S. H. Alves4, R. C. R. Beck5, M. L. Athayde5 Received February 15, 2007, accepted March 8, 2007 Prof. Dr. Margareth Linde Athayde, Departamento de Farma´cia Industrial, Pre´dio 26, sala 1115, Campus Camobi, Universidade Federal de Santa Maria, RS, Brasil. CEP 97105-900 [email protected] Pharmazie 62: 876–880 (2007) doi: 10.1691/ph.2007.11.7052 Ilex paraguariensis is used in Brazil as a stimulating beverage called “mate”. Leaves and immature fruit extracts of Ilex paraguariensis were evaluated for their radical scavenging capacity, total methyl- xanthine and polyphenol contents. Antimicrobial activity of two enriched saponin fractions obtained from the fruits were also evaluated. The radical scavenging activity of the fractioned extracts was determined spectrophotometrically using 1,1-diphenylpicrylhydrazyl free radical (DPPH). The IC50 of l-ascorbic acid, ethyl acetate and n-butanol fractions from the leaves and ethyl acetate fraction from the fruits were 6.48 mg/mL, 13.26 mg/mL, 27.22 mg/mL, and 285.78 mg/mL, respectively. Total methylxanthine content was 1.16 Æ 0.06 mg/g dry weight in the fruits and 8.78 Æ 0.01 mg/g in the leaves. -
L-Citrulline
L‐Citrulline Pharmacy Compounding Advisory Committee Meeting November 20, 2017 Susan Johnson, PharmD, PhD Associate Director Office of Drug Evaluation IV Office of New Drugs L‐Citrulline Review Team Ben Zhang, PhD, ORISE Fellow, OPQ Ruby Mehta, MD, Medical Officer, DGIEP, OND Kathleen Donohue, MD, Medical Officer, DGIEP, OND Tamal Chakraborti, PhD, Pharmacologist, DGIEP, OND Sushanta Chakder, PhD, Supervisory Pharmacologist, DGIEP, OND Jonathan Jarow, MD, Advisor, Office of the Center Director, CDER Susan Johnson, PharmD, PhD, Associate Director, ODE IV, OND Elizabeth Hankla, PharmD, Consumer Safety Officer, OUDLC, OC www.fda.gov 2 Nomination • L‐citrulline has been nominated for inclusion on the list of bulk drug substances for use in compounding under section 503A of the Federal Food, Drug and Cosmetic Act (FD&C Act) • It is proposed for oral use in the treatment of urea cycle disorders (UCDs) www.fda.gov 3 Physical and Chemical Characterization • Non‐essential amino acid, used in the human body in the L‐form • Well characterized substance • Soluble in water • Likely to be stable under ordinary storage conditions as solid or liquid oral dosage forms www.fda.gov 4 Physical and Chemical Characterization (2) • Possible synthetic routes – L‐citrulline is mainly produced by fermentation of L‐arginine as the substrate with special microorganisms such as the L‐arginine auxotrophs arthrobacterpa rafneus and Bacillus subtilis. – L‐citrulline can also be obtained through chemical synthesis. The synthetic route is shown in the scheme below. This -
Identification of the 100 Richest Dietary Sources of Polyphenols: an Application of the Phenol-Explorer Database
European Journal of Clinical Nutrition (2010) 64, S112–S120 & 2010 Macmillan Publishers Limited All rights reserved 0954-3007/10 www.nature.com/ejcn ORIGINAL ARTICLE Identification of the 100 richest dietary sources of polyphenols: an application of the Phenol-Explorer database JPe´rez-Jime´nez1,2, V Neveu1,2,FVos1,2 and A Scalbert1,2 1Clermont Universite´, Universite´ d’Auvergne, Unite´ de Nutrition Humaine, Saint-Genes-Champanelle, France and 2INRA, UMR 1019, UNH, CRNH Auvergne, Saint-Genes-Champanelle, France Background/Objectives: The diversity of the chemical structures of dietary polyphenols makes it difficult to estimate their total content in foods, and also to understand the role of polyphenols in health and the prevention of diseases. Global redox colorimetric assays have commonly been used to estimate the total polyphenol content in foods. However, these assays lack specificity. Contents of individual polyphenols have been determined by chromatography. These data, scattered in several hundred publications, have been compiled in the Phenol-Explorer database. The aim of this paper is to identify the 100 richest dietary sources of polyphenols using this database. Subjects/Methods: Advanced queries in the Phenol-Explorer database (www.phenol-explorer.eu) allowed retrieval of information on the content of 502 polyphenol glycosides, esters and aglycones in 452 foods. Total polyphenol content was calculated as the sum of the contents of all individual polyphenols. These content values were compared with the content of antioxidants estimated using the Folin assay method in the same foods. These values were also extracted from the same database. Amounts per serving were calculated using common serving sizes.