DOCSLIB.ORG

Lignans and Their Derivatives from Plants As Antivirals

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Lignans and Their Derivatives from Plants As Antivirals molecules Review Lignans and Their Derivatives from Plants as Antivirals Qinghua Cui 1,2,3,*, Ruikun Du 1,2,3 , Miaomiao Liu 1 and Lijun Rong 4,* 1 College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China; [email protected] (R.D.); [email protected] (M.L.) 2 Qingdao Academy of Chinese Medicinal Sciences, Shandong University of Traditional Chinese Medicine, Qingdao 266122, China 3 Research Center, Shandong University of Traditional Chinese Medicine, Jinan 250355, China 4 Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA * Correspondence: [email protected] (Q.C.); [email protected] (L.R.); Tel.: +86-186-6017-1818 (Q.C.); +1-312-996-0110 (L.R.) Academic Editor: David Barker Received: 8 November 2019; Accepted: 23 December 2019; Published: 1 January 2020 Abstract: Lignans are widely produced by various plant species; they are a class of natural products that share structural similarity. They usually contain a core scaffold that is formed by two or more phenylpropanoid units. Lignans possess diverse pharmacological properties, including their antiviral activities that have been reported in recent years. This review discusses the distribution of lignans in nature according to their structural classification, and it provides a comprehensive summary of their antiviral activities. Among them, two types of antiviral lignans—podophyllotoxin and bicyclol, which are used to treat venereal warts and chronic hepatitis B (CHB) in clinical, serve as examples of using lignans for antivirals—are discussed in some detail. Prospects of lignans in antiviral drug discovery are also discussed. Keywords: lignans; antivirals; mechanism; drug development 1. Introduction Lignans are a large group of naturally occurring compounds that are derived from the shikimic acid biosynthetic pathway [1]. Structurally, Lignans contain a basic scaffold of two or more phenylpropanoid units [2], and the monomers forming lignans are cinnamic acid, cinnamyl alcohol, propenyl benzene, and allyl benzene. When the molecular linkage of monomers occurs between positions β-β0 (also referred to as an 8-80), these compounds are designated as “classical lignans”. In contrast, the compounds are grouped into “neolignans” if the main structural units are coupled in any other way (non β-β0 linkage). Figure1 shows the monomers and the classification. Neolignans have more varied structures than classical lignans. Lignans are widely distributed in the plant kingdom, and they exist in plant roots, rhizomes, stems, leaves, flowers, fruits, seeds, xylem, and resins. Plants, such as the Lauraceae family, especially the genera of Machilus, Ocotea, and Nectandra are rich sources of lignans. Additionally, Annonaceae, Orchidaceae, Berberidaceae, and Schisandraceae family contain a large number of constituents of lignans and neolignans [3–5]. Up to date, lignans are found in over 70 families in plant kingdom, and more than 200 classical lignans and 100 neolignans have been characterized [6]. They are usually present as dimers, but some of them are trimers or tetramers. Most of the lignans in plants are in a free state, while some of them can combine with glycon and form glycosides and other derivatives. Molecules 2020, 25, 183; doi:10.3390/molecules25010183 www.mdpi.com/journal/molecules Molecules 2020, 25, 183 2 of 17 Molecules 2019, 24, x 2 of 19 FigureFigure 1. The 1. The monomers monomers and and thisthis classification classification of lignans. of lignans. With such structural diversity of lignans being discovered, it is not surprising that many attractive Withpharmacological such structural activities diversity of the lignan of lignans family, such being as antitumor discovered, [7], antioxidant it is not [5], surprising antibacterial [that8], many attractiveimmunosuppressive pharmacological [9 ],activities and antiasthmatic of the propertieslignan family, [10] were such reported. as antitumor Pertinent to[7], this antioxidant review, [5], antibacterialmany [8], lignans immunosuppressive have been identified with [9], antiviral and antias activitiesthmatic [11]. Tubulinproperties binding, [10] reverse were transcriptasereported. Pertinent to this review,inhibition, many integrase lignans inhibition, have and been topoisomerase identified inhibition with areantiviral included activities as the reported [11]. mechanisms Tubulin binding, of antiviral activities [12]. Here, we will highlight the antiviral activities and mechanisms of action reverse transcriptase inhibition, integrase inhibition, and topoisomerase inhibition are included as (MOA) of different lignans and their derivatives. the reported mechanisms of antiviral activities [12]. Here, we will highlight the antiviral activities and mechanisms2. Antiviral of E ffactionect and (MOA) MOA of different lignans and their derivatives. Lignans display a vast structural diversity due to the numerous potential coupling modes of the 2. Antiviralphenoxy Effect radicals and [ 13MOA]. As mentioned above, they can be grouped into two subclasses: classical lignans and neolignans. Next, we will discuss the antiviral lignans and possible MOA, according to different Lignanssubclasses, display and thena vast summarize structural them diversity in Table1 dueat the to end the of numerous this section. potential coupling modes of the phenoxy radicals [13]. As mentioned above, they can be grouped into two subclasses: classical lignans 2.1. Classical Lignans and neolignans. Next, we will discuss the antiviral lignans and possible MOA, according to different subclasses, andThe then classical summarize lignans contain them dimeric in Table structures 1 at the that end are of formedthis section. by a β -β0-linkage between two phenyl propane units, some of them with a different degree of oxidation in the side-chain and a different substitution pattern in the aromatic moieties. They can be classified into six 2.1. Classical Lignans major subtypes—dibenzylbutanes, dibenzylbutyrolactones, arylnaphthalenes/aryltetralins, substituted Thetetrahydro-furans, classical lignans 2,6-diarylfurofurans, contain dimeric andstructures dibenzocyclooctadienes that are formed [6,14 by]. Figurea β-β′2-linkage illustrates between the two phenyl propanestructures andunits, relationships some of amongthem them.with a different degree of oxidation in the side-chain and a different substitution pattern in the aromatic moieties. They can be classified into six major subtypes—dibenzylbutanes, dibenzylbutyrolactones, arylnaphthalenes/aryltetralins, substituted tetrahydro-furans, 2,6-diarylfurofurans, and dibenzocyclooctadienes [6,14]. Figure 2 illustrates the structures and relationships among them. Molecules 2020, 25, 183 3 of 17 Molecules 2019, 24, x 3 of 19 Molecules 2019, 24, x 4 of 19 TMP is the shorter title of tetra-O-methyl nordihydroguaiaretic acid. It is a methylated derivative of NDGAFigure and 2.2. Relationships Relationshipswas also initially between between founded di ffdifferenterent classicalin theclassical resin lignans. lignans.of the It depicts creosote It depicts the basicbush the mother [26].basic As nucleusmother the derivative structurenucleus of NDGA,ofstructure di itff erentwas of subtypestested different the of subtypes antiviral classical of lignans, effectsclassical the agains lignans, maint structuralWNV the main and feature structural ZIKV of simultaneously this feature subclass of this is the subclass withβ-β0 NDGA;linkage. is the the resultsDibenzylbutaneβ- β′showed linkage. both Dibenzylbutane (central compounds position) (central inhibited is theposition) basic the structure isinfe thection basic of ofstructure classical WNV lignan,ofand classical ZIKA, other lignan, with subtypes othergood of subtypes and lignans similar derive from this structure with different chemical reactions. IC50 values,of lignans and derive MOA from was this likely structur by impairinge with different viral chemical replication reactions. [24]. Meanwhile, Pollara showed that TMP2.1.1. inhibits Dibenzylbutanes poxvirus growth in vitro by preventing the efficient spread of virus particles from cell to2.1.1. cell Dibenzylbutanes [27]. Additionally, there were some reports regarding the antiviral activity of TMP against herpesDibenzylbutanes, simplex virus (HSV)which andare alsohuman known immunodeficiency as simple lignans, virus are (HIV) the simplest [28,29]. Moreover,classical lignans, it was whichmade intoare are the thevaginal only only lignanointment lignan subtype subtype for women without without with being being HPV-linked cyclized. cyclized. They cervical They are phenylpropane areintraepithelial phenylpropane dimersneoplasia dimers that and have that it β β showedhavea β-β′ alinkage. an- excellent0 linkage. Dibenzylbutane safety Dibenzylbutane profile lignans in Phase lignansalso I/II show trials also an [30]. show increased an increased diversity diversity due to multiple due to multiplepossible possibleoxidationBesides, oxidation states Xu isolatedalong states the alongfour butane new the butanelignanschain [15]. chainfrom Niranthin, [the15]. aerial Niranthin, partsnordihydroguaiaretic of nordihydroguaiaretic Justicia procumbens acid (Acanthaceae)(NDGA), acid (NDGA), and andterameprocol terameprocoltested their (TMP), activity (TMP), are againstthe are representative the HIV-1. representative One compound of compoundsthe news with secoisolariciresinol withantiviral antiviral activity activity dimethylether in this in subclass, this subclass, acetate and and Figure3
Load more

Recommended publications
  • Report of the Advisory Group to Recommend Priorities for the IARC Monographs During 2020–2024
    IARC Monographs on the Identification of Carcinogenic Hazards to Humans Report of the Advisory Group to Recommend Priorities for the IARC Monographs during 2020–2024 Report of the Advisory Group to Recommend Priorities for the IARC Monographs during 2020–2024 CONTENTS Introduction ................................................................................................................................... 1 Acetaldehyde (CAS No. 75-07-0) ................................................................................................. 3 Acrolein (CAS No. 107-02-8) ....................................................................................................... 4 Acrylamide (CAS No. 79-06-1) .................................................................................................... 5 Acrylonitrile (CAS No. 107-13-1) ................................................................................................ 6 Aflatoxins (CAS No. 1402-68-2) .................................................................................................. 8 Air pollutants and underlying mechanisms for breast cancer ....................................................... 9 Airborne gram-negative bacterial endotoxins ............................................................................. 10 Alachlor (chloroacetanilide herbicide) (CAS No. 15972-60-8) .................................................. 10 Aluminium (CAS No. 7429-90-5) .............................................................................................. 11
    [Show full text]
  • Insecticides - Development of Safer and More Effective Technologies
    INSECTICIDES - DEVELOPMENT OF SAFER AND MORE EFFECTIVE TECHNOLOGIES Edited by Stanislav Trdan Insecticides - Development of Safer and More Effective Technologies http://dx.doi.org/10.5772/3356 Edited by Stanislav Trdan Contributors Mahdi Banaee, Philip Koehler, Alexa Alexander, Francisco Sánchez-Bayo, Juliana Cristina Dos Santos, Ronald Zanetti Bonetti Filho, Denilson Ferrreira De Oliveira, Giovanna Gajo, Dejane Santos Alves, Stuart Reitz, Yulin Gao, Zhongren Lei, Christopher Fettig, Donald Grosman, A. Steven Munson, Nabil El-Wakeil, Nawal Gaafar, Ahmed Ahmed Sallam, Christa Volkmar, Elias Papadopoulos, Mauro Prato, Giuliana Giribaldi, Manuela Polimeni, Žiga Laznik, Stanislav Trdan, Shehata E. M. Shalaby, Gehan Abdou, Andreia Almeida, Francisco Amaral Villela, João Carlos Nunes, Geri Eduardo Meneghello, Adilson Jauer, Moacir Rossi Forim, Bruno Perlatti, Patrícia Luísa Bergo, Maria Fátima Da Silva, João Fernandes, Christian Nansen, Solange Maria De França, Mariana Breda, César Badji, José Vargas Oliveira, Gleberson Guillen Piccinin, Alan Augusto Donel, Alessandro Braccini, Gabriel Loli Bazo, Keila Regina Hossa Regina Hossa, Fernanda Brunetta Godinho Brunetta Godinho, Lilian Gomes De Moraes Dan, Maria Lourdes Aldana Madrid, Maria Isabel Silveira, Fabiola-Gabriela Zuno-Floriano, Guillermo Rodríguez-Olibarría, Patrick Kareru, Zachaeus Kipkorir Rotich, Esther Wamaitha Maina, Taema Imo Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2013 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work.
    [Show full text]
  • Pinoresinol Reductase 1 Impacts Lignin Distribution During Secondary Cell Wall Biosynthesis in Arabidopsis
    Phytochemistry xxx (2014) xxx–xxx Contents lists available at ScienceDirect Phytochemistry journal homepage: www.elsevier.com/locate/phytochem Pinoresinol reductase 1 impacts lignin distribution during secondary cell wall biosynthesis in Arabidopsis Qiao Zhao a, Yining Zeng b,e, Yanbin Yin c, Yunqiao Pu d,e, Lisa A. Jackson a,e, Nancy L. Engle e,f, Madhavi Z. Martin e,f, Timothy J. Tschaplinski e,f, Shi-You Ding b,e, Arthur J. Ragauskas d,e, ⇑ Richard A. Dixon a,e,g, a Plant Biology Division, Samuel Roberts Noble Foundation, 2510 Sam Noble Parkway, Ardmore, OK 73401, USA b Biosciences Center, National Renewable Energy Laboratory, Golden, CO 80401, USA c Department of Biological Sciences, Northern Illinois University, DeKalb, IL 60115, USA d Institute of Paper Science and Technology, Georgia Institute of Technology, Atlanta, GA, USA e BioEnergy Science Center (BESC), Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA f Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA g Department of Biological Sciences, University of North Texas, Denton, TX 76203, USA article info abstract Article history: Pinoresinol reductase (PrR) catalyzes the conversion of the lignan (À)-pinoresinol to (À)-lariciresinol in Available online xxxx Arabidopsis thaliana, where it is encoded by two genes, PrR1 and PrR2, that appear to act redundantly. PrR1 is highly expressed in lignified inflorescence stem tissue, whereas PrR2 expression is barely detect- Keywords: able in stems. Co-expression analysis has indicated that PrR1 is co-expressed with many characterized Lignan genes involved in secondary cell wall biosynthesis, whereas PrR2 expression clusters with a different Lignin set of genes.
    [Show full text]
  • 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.
    [Show full text]
  • Hinokinin, an Emerging Bioactive Lignan
    Molecules 2014, 19, 14862-14878; doi:10.3390/molecules190914862 OPEN ACCESS molecules ISSN 1420-3049 www.mdpi.com/journal/molecules Review Hinokinin, an Emerging Bioactive Lignan Maria Carla Marcotullio *, Azzurra Pelosi and Massimo Curini Department of Pharmaceutical Sciences, University of Perugia, via del Liceo 1, 06123 Perugia, Italy; E-Mails: [email protected] (A.P.); [email protected] (M.C.) * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +39-075-585-5100; Fax: +39-075-585-5116. Received: 24 June 2014; in revised form: 10 September 2014 / Accepted: 10 September 2014 / Published: 17 September 2014 Abstract: Hinokinin is a lignan isolated from several plant species that has been recently investigated in order to establish its biological activities. So far, its cytotoxicity, its anti-inflammatory and antimicrobial activities have been studied. Particularly interesting is its notable anti-trypanosomal activity. Keywords: cubebinolide; cytotoxicity; Trypanosoma; Chagas disease; antigenotoxic activity 1. Introduction Lignans are important components of foods and medicines biosynthetically deriving from the radical coupling of two molecules of coniferyl alcohol at C-8/C-8′ positions (Figure 1). They are classified in different groups—dibenzylfuran, dihydroxybenzylbutane, dibenzylbutyrolactol, dibenzylbutyrolactone, aryltetraline lactone and arylnaphtalene derivatives—on the basis of the skeleton oxidation [1] and of the way in which oxygen is incorporated into the skeleton [2] (Figure 1). Podophyllotoxin and deoxypodophyllotoxin are, perhaps, the most important biologically active lignans, and their properties have been broadly reviewed [3,4]. In these last years, the biological activities of several lignans have been studied in depth [5–7] and among them hinokinin (1) is emerging as a new interesting compound.
    [Show full text]
  • Preparation of Flaxseed for Lignan Determination by Gas Chromatography-Mass Spectrometry Method
    Czech J. Food Sci. Vol. 30, 2012, No. 1: 45–52 Preparation of Flaxseed for Lignan Determination by Gas Chromatography-Mass Spectrometry Method Hrvoje SARAJLIJA2, Nikolina ČUKELj 1, Dubravka NOVOTNI1, Gordan MRšIć 2, Mladen BRnčIć 1 and Duška ćURIć 1 1Faculty of Food Technology and Biotechnology, University of Zagreb, Zagreb, Croatia; 2Forensic Science Centre “Ivan Vučetić”, Croatian Ministry of the Interior, Zagreb, Croatia Abstract Sarajlija H., Čukelj N., Novotni D., Mršić G., Brnčić M., Ćurić D. (2012): Preparation of flaxseed for lignan determination by gas chromatography-mass spectrometry method. Czech J. Food Sci., 30: 45–52. Since 1980s, several methods for the determination of lignans in food samples have been developed depending on the types of lignans and foods analysed, but mostly on flaxseed as a reference food. In this work, specific steps in flaxseed preparation for lignan secoisolariciresinol analysis by gas chromatography-mass spectrometry method were examined. Ethanol extraction of lignan from defatted and non-defatted flaxseed before acid hydrolysis yielded significantly lower concentrations (5172 ± 49 μg/g; 5159 ± 83 μg/g, respectively), when compared to the direct acid hydrolysis (8566 ± 169 μg/g; 8571 ± 192 μg/g, respectively). In the analysed samples of defatted and dried flaxseed, no significant differ- ence in lignan content was observed when compared to non-defatted flaxseed samples. Keywords: defatting; extraction; GC/MS; hydrolysis; lignans Lignans are defined as a group of phenylpropa- studies on lignans have arisen, giving focus to all noid dimers, in which the phenylpropane units are the aspects of lignan analysis – from their occur- linked by the central carbon (C8) of their propyl rence in nature to their bioactivity in the human side chains.
    [Show full text]
  • A Comprehensive Review on Phyllanthus Derived Natural Products As Potential Chemotherapeutic and Immunomodulators for a Wide Range of T Human Diseases
    Biocatalysis and Agricultural Biotechnology 17 (2019) 529–537 Contents lists available at ScienceDirect Biocatalysis and Agricultural Biotechnology journal homepage: www.elsevier.com/locate/bab A comprehensive review on Phyllanthus derived natural products as potential chemotherapeutic and immunomodulators for a wide range of T human diseases Mohamed Ali Seyed Department of Clinical Biochemistry, Faculty of Medicine, University of Tabuk, Tabuk 71491, Saudi Arabia ARTICLE INFO ABSTRACT Keywords: Treatment options for most cancers are still insufficient, despite developments and technology advancements. It Cancer has been postulated that the immune response to progressive tumors is insufficient due to a deficiency in afferent Phyllanthus amarus/niruri mechanisms responsible for the development of tumor-reactive T cells. Many patients treated for cancer will Phyllanthin have their cancer recurrence, often after a long remission period. This suggests that there are a small number of Hypophyllanthin tumor cells that remain alive after standard treatment(s) – alone or in combination and have been less effective Chemotherapeutic in combating metastasis that represents the most elaborate hurdle to overcome in the cure of the disease. Immunomodulation Therefore, any new effective and safe therapeutic agents will be highly demanded. To circumvent many plant extracts have attributed for their chemoprotective potentials and their influence on the human immune system. It is now well recognized that immunomodulation of immune response could provide an alternative or addition to conventional chemotherapy for a variety of disease conditions. However, many hurdles still exist. In recent years, there has been a tremendous interest either in harnessing the immune system or towards plant-derived immunomodulators as anticancer agents for their efficacy, safety and their targeted drug action and drug de- livery mechanisms.
    [Show full text]
  • Silibinin Exerts Cancer Chemopreventive Efficacy Via
    SILIBININ EXERTS CANCER CHEMOPREVENTIVE EFFICACY VIA TARGETING PROSTATE CANCER CELL AND CANCER-ASSOCIATED FIBROBLAST INTERACTION By HAROLD J. TING M.S. Western University of Health Sciences, 2010 B.S. University of California, Berkeley, 2002 A thesis submitted to the Faculty of the Graduate School of the University of Colorado in partial fulfillment of the requirements for the degree of Doctor of Philosophy Pharmaceutical Sciences 2015 This thesis for the Doctor of Philosophy degree by Harold J. Ting has been approved for the Pharmaceutical Sciences Program by Tom Anchordoquy, Chair Rajesh Agarwal, Advisor David Ross Robert Sclafani Gagan Deep Date__12/18/15_____________ ii Harold J. Ting (Ph.D., Pharmaceutical Sciences) Silibinin Exerts Cancer Chemopreventive Efficacy via Targeting Prostate Cancer Cell and Cancer-Associated Fibroblast Interaction Thesis directed by Professor Rajesh Agarwal ABSTRACT Prostate cancer (PCA) kills thousands in the US each year despite massive investment and success in improving early detection and treatment. Importantly, even successful treatment is still associated with persistent and often highly disruptive adverse health effects on the patient. As a consequence, the development of alternative treatment regimens like chemoprevention remains of great interest. Chemoprevention is intended for long-term and continuous use to prevent or halt disease even in individuals with no outward sign of disease. A developing tumor and its surrounding tumor microenvironment (TME) can be together thought of as a nascent organ, with specific components carrying out distinct functions. To study these interactions, we developed a cell culture system that would isolate the secretions of PCA cells and cancer associated fibroblasts (CAFs) to identify their effects on TME elements which might support PCA progression.
    [Show full text]
  • Dr. Duke's Phytochemical and Ethnobotanical Databases List of Chemicals for Intermittent Claudication
    Dr. Duke's Phytochemical and Ethnobotanical Databases List of Chemicals for Intermittent Claudication Chemical Activity Count (+)-ALPHA-VINIFERIN 1 (+)-CATECHIN 6 (+)-EUDESMA-4(14),7(11)-DIENE-3-ONE 1 (+)-GALLOCATECHIN 1 (+)-HERNANDEZINE 1 (+)-ISOCORYDINE 1 (+)-PRAERUPTORUM-A 1 (+)-PSEUDOEPHEDRINE 1 (+)-SYRINGARESINOL 1 (-)-16,17-DIHYDROXY-16BETA-KAURAN-19-OIC 1 (-)-ACETOXYCOLLININ 1 (-)-ALPHA-BISABOLOL 1 (-)-BETONICINE 1 (-)-BISPARTHENOLIDINE 1 (-)-BORNYL-CAFFEATE 2 (-)-BORNYL-FERULATE 2 (-)-BORNYL-P-COUMARATE 2 (-)-EPIAFZELECHIN 1 (-)-EPICATECHIN 5 (-)-EPICATECHIN-3-O-GALLATE 1 (-)-EPIGALLOCATECHIN 1 (-)-EPIGALLOCATECHIN-3-O-GALLATE 2 (-)-EPIGALLOCATECHIN-GALLATE 4 (-)-HYDROXYJASMONIC-ACID 1 (-)-N-(1'-DEOXY-1'-D-FRUCTOPYRANOSYL)-S-ALLYL-L-CYSTEINE-SULFOXIDE 1 (1'S)-1'-ACETOXYCHAVICOL-ACETATE 2 (15:1)-CARDANOL 1 Chemical Activity Count (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 2 0-METHYLCORYPALLINE 2 1,2,6-TRI-O-GALLOYL-BETA-D-GLUCOSE 1 1,7-BIS(3,4-DIHYDROXYPHENYL)HEPTA-4E,6E-DIEN-3-ONE 1 1,7-BIS(4-HYDROXY-3-METHOXYPHENYL)-1,6-HEPTADIEN-3,5-DIONE 1 1,7-BIS-(4-HYDROXYPHENYL)-1,4,6-HEPTATRIEN-3-ONE 1 1,8-CINEOLE 1 1-(METHYLSULFINYL)-PROPYL-METHYL-DISULFIDE 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 2 10-DEHYDROGINGERDIONE 1 10-GINGERDIONE 1 12-METHOXYDIHYDROCOSTULONIDE 1 13',II8-BIAPIGENIN 2 13-OXYINGENOL-ESTER 1 14-ACETOXYCEDROL 3 16,17-DIHYDROXY-16BETA-KAURAN-19-OIC
    [Show full text]
  • Anticancer Mechanisms of Flaxseed and Its Derived Mammalian
    ANTICANCER MECHANISMS OF FLAXSEED AND ITS DERIVED MAMMALIAN LIGNAN ENTEROLACTONE IN LUNG A Dissertation Submitted to the Graduate Faculty of the North Dakota State University of Agriculture and Applied Science By Shireen Chikara In Partial Fulfillment of the Requirements for the Degree of DOCTOR OF PHILOSOPHY Major Program: Cellular and Molecular Biology April 2017 Fargo, North Dakota North Dakota State University Graduate School Title ANTICANCER MECHANISMS OF FLAXSEED AND ITS DERIVED MAMMALIAN LIGNAN ENTEROLACTONE IN LUNG By Shireen Chikara The Supervisory Committee certifies that this disquisition complies with North Dakota State University’s regulations and meets the accepted standards for the degree of DOCTOR OF PHILOSOPHY SUPERVISORY COMMITTEE: Dr. Katie Reindl Chair Dr. Jane Schuh Dr. Yeong Rhee Dr. Steven Qian Approved: 04-13-2017 Dr. Jane Schuh Date Department Chair ABSTRACT Whole flaxseed and its derived lignans have shown anti-cancer properties in a variety of malignancies. However, their potential remains uninvestigated in lung cancer, the leading cause of cancer-related deaths worldwide. We investigated the anti-tumor effects of flaxseed-derived mammalian lignan enterolactone (EL) in human lung cancer cell cultures and the chemopreventive potential of 10% whole flaxseed in a mouse model of lung carcinogenesis. We found that EL inhibits in vitro proliferation and motility of a panel of non-small cell lung cancer cell (NSCLC) lines. EL-mediated inhibition in lung cancer cell proliferation was due to a decrease in mRNA and protein expression levels of G1-phase cell cycle promoters and a simultaneous increase in mRNA and protein expression levels of p21WAF1/CIP1, a negative regulator of the G1-phase.
    [Show full text]
  • Silibinin Inhibits LPS-Induced Macrophage Activation by Blocking P38 MAPK in RAW 264.7 Cells
    Original Article Biomol Ther 21(4), 258-263 (2013) Silibinin Inhibits LPS-Induced Macrophage Activation by Blocking p38 MAPK in RAW 264.7 Cells Cha Kyung Youn1,2, Seon Joo Park1,2, Min Young Lee1,2, Man Jin Cha2, Ok Hyeun Kim2, Ho Jin You1,2, In Youp Chang1,3, Sang Pil Yoon4 and Young Jin Jeon1,2,* 1DNA Damage Response Network Center, Departments of 2Pharmacology, 3Anatomy, School of Medicine, Chosun University, Gwangju 501-759, 4Department of Anatomy, School of Medicine, Jeju National University, Jeju 690-756, Republic of Korea Abstract We demonstrate herein that silibinin, a polyphenolic fl avonoid compound isolated from milk thistle (Silybum marianum), inhibits LPS-induced activation of macrophages and production of nitric oxide (NO) in RAW 264.7 cells. Western blot analysis showed silibinin inhibits iNOS gene expression. RT-PCR showed that silibinin inhibits iNOS, TNF-α, and IL1β. We also showed that silib- inin strongly inhibits p38 MAPK phosphorylation, whereas the ERK1/2 and JNK pathways are not inhibited. The p38 MAPK inhibi- tor abrogated the LPS-induced nitrite production, whereas the MEK-1 inhibitor did not affect the nitrite production. A molecular modeling study proposed a binding pose for silibinin targeting the ATP binding site of p38 MAPK (1OUK). Collectively, this series of experiments indicates that silibinin inhibits macrophage activation by blocking p38 MAPK signaling. Key Words: Silibinin, Macrophages, p38 MAPK, Nitric oxide INTRODUCTION signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) Silibinin is the major active constituent of silymarin, a stan- (Su and Karin, 1996).
    [Show full text]
  • Recent Advances in Research on Lignans and Neolignans Cite This: Nat
    Natural Product Reports View Article Online REVIEW View Journal | View Issue Recent advances in research on lignans and neolignans Cite this: Nat. Prod. Rep.,2016,33, 1044 ab a a Remy´ Bertrand Teponno,† Souvik Kusari† and Michael Spiteller* Covering: 2009 to 2015 Lignans and neolignans are a large group of natural products derived from the oxidative coupling of two C6–C3 units. Owing to their biological activities ranging from antioxidant, antitumor, anti-inflammatory to antiviral properties, they have been used for a long time both in ethnic as well as in conventional medicine. This review describes 564 of the latest examples of naturally occurring lignans and neolignans, and their glycosides in some cases, which have been isolated between 2009 and 2015. It comprises the Received 15th February 2016 data reported in more than 200 peer-reviewed articles and covers their source, isolation, structure DOI: 10.1039/c6np00021e Creative Commons Attribution-NonCommercial 3.0 Unported Licence. elucidation and bioactivities (where available), and highlights the biosynthesis and total synthesis of some www.rsc.org/npr important ones. 1 Introduction 1 Introduction 1.1 Denition 1.2 Biosynthesis and distribution of lignans and neolignans The last decade has witnessed a renewed interest in biologically 1.3 Hyphenated techniques used for the isolation, identi- active compounds isolated from a plethora of natural resources, cation and quantication of lignans and neolignans in addition to impressive progress in allied methodologies such This article is licensed under a 2 Lignans as combinatorial chemistry and high-throughput screening. 2.1 Dibenzocyclooctadiene derivatives Given the advantages of formulations containing compounds 2.2 Arylnaphthalene and aryltetralin derivatives obtained from natural resources over compounds obtained by 2.3 Dibenzylbutane, dibenzylbutyrolactol and dibenzylbutyr- total synthesis, including relatively low toxicity, complete Open Access Article.
    [Show full text]