DOCSLIB.ORG

Marine-Derived Biologically Active Compounds for the Potential Treatment of Rheumatoid Arthritis

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Marine-Derived Biologically Active Compounds for the Potential Treatment of Rheumatoid Arthritis marine drugs Review Marine-Derived Biologically Active Compounds for the Potential Treatment of Rheumatoid Arthritis Muhammad Bilal 1,* , Maimoona Qindeel 2, Leonardo Vieira Nunes 3 , Marco Thúlio Saviatto Duarte 4 , Luiz Fernando Romanholo Ferreira 5,6 , Renato Nery Soriano 7 and Hafiz M. N. Iqbal 8,* 1 School of Life Science and Food Engineering, Huaiyin Institute of Technology, Huaian 223003, China 2 Department of Pharmacy, Quaid-i-Azam University, Islamabad 45320, Pakistan; [email protected] 3 Department of Medicine, Federal University of Juiz de Fora, Juiz de Fora-MG 36036-900, Brazil; [email protected] 4 Department of Medicine, Federal University of Juiz de Fora, Governador Valadares-MG 35010-180, Brazil; [email protected] 5 Graduate Program in Process Engineering, Tiradentes University (UNIT), Av. Murilo Dantas, 300, Farolândia, Aracaju-Sergipe 49032-490, Brazil; [email protected] 6 Institute of Technology and Research (ITP), Tiradentes University (UNIT), Av. Murilo Dantas, 300, Farolândia, Aracaju-Sergipe 49032-490, Brazil 7 Division of Physiology and Biophysics, Department of Basic Life Sciences, Federal University of Juiz de Fora, Governador Valadares-MG 35010-180, Brazil; [email protected] 8 School of Engineering and Sciences, Tecnologico de Monterrey, Monterrey 64849, Mexico * Correspondence: [email protected] or [email protected] (M.B.); hafi[email protected] (H.M.N.I.) Abstract: Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease with a prevalence rate of up to 1% and is significantly considered a common worldwide public health concern. Com- mercially, several traditional formulations are available to treat RA to some extent. However, these synthetic compounds exert toxicity and considerable side effects even at lower therapeutic concentra- tions. Considering the above-mentioned critiques, research is underway around the world in finding and exploiting potential alternatives. For instance, marine-derived biologically active compounds Citation: Bilal, M.; Qindeel, M.; have gained much interest and are thus being extensively utilized to confront the confines of in Nunes, L.V.; Duarte, M.T.S.; Ferreira, practice counterparts, which have become ineffective for 21st-century medical settings. The utiliza- L.F.R.; Soriano, R.N.; Iqbal, H.M.N. tion of naturally available bioactive compounds and their derivatives can minimize these synthetic Marine-Derived Biologically Active compounds’ problems to treat RA. Several marine-derived compounds exhibit anti-inflammatory Compounds for the Potential and antioxidant properties and can be effectively used for therapeutic purposes against RA. The Treatment of Rheumatoid Arthritis. results of several studies ensured that the extraction of biologically active compounds from marine Mar. Drugs 2021, 19, 10. https://doi. sources could provide a new and safe source for drug development against RA. Finally, current org/10.3390/md19010010 challenges, gaps, and future perspectives have been included in this review. Received: 19 November 2020 Keywords: rheumatoid arthritis; marine-derived compounds; anti-inflammatory; drug development; Accepted: 10 December 2020 biomedical applications Published: 29 December 2020 Publisher’s Note: MDPI stays neu- tral with regard to jurisdictional claims in published maps and institutional 1. Introduction affiliations. Rheumatoid arthritis (RA) is a chronic autoimmune disorder that affects the synovial joints lining and is allied with progressive disability, mortality, and socioeconomic burdens. The disease is more common in women than men, with a prevalence rate of 1%. The clinical sign and symptoms of RA include swelling, arthralgia, the loss of mobility, and Copyright: © 2020 by the authors. Li- redness of the joints [1,2]. The early diagnosis of RA is considered as the critical parameter censee MDPI, Basel, Switzerland. This to prevent disease progression. In the past 20 years, a significant advancement in the article is an open access article distributed diagnosis and management of the disease has occurred. However, the early diagnosis under the terms and conditions of the remains challenging because it depends on the clinical information collected from the Creative Commons Attribution (CC BY) license (https://creativecommons.org/ patient’s clinical and physical examination, including blood test and imaging results [3,4]. licenses/by/4.0/). The pathogenesis of RA is allied with genetic factors and stimulated by environmental Mar. Drugs 2021, 19, 10. https://doi.org/10.3390/md19010010 https://www.mdpi.com/journal/marinedrugs Mar. Drugs 2021Mar., Drugs19, 10 2020 , 18, x 2 of 23 2 of 21 However, the early diagnosis remains challenging because it depends on the clinical information collected from the patient’s clinical and physical examination, including blood test and imaging factors. It is proposed that almost 60–65% of RA cases are due to genetic factors. There results [3,4]. The pathogenesis of RA is allied with genetic factors and stimulated by environmental are nearly 100 loci that are responsible for the progression of RA [5,6]. Among the several factors. It is proposed that almost 60–65% of RA cases are due to genetic factors. There are nearly 100 loci, the most common loci associated with RA contains information for the expression of loci that are responsiblemajor for histocompatibility the progression of complex RA [5,6]. (MHC Among class-II), the several especially loci, the HLADRO1/O4. most common Addition- loci associated with RAally, contains the loci thatinformation express thefor th post-translationale expression of major modified histocompatibility enzyme, intercellular complex regulatory (MHC class-II), especiallypathways, HLADRO1/O4. and costimulatory Additionally pathways, the alsoloci that contribute express towards the post-translational disease progression [7]. modified enzyme, intercellularThe environmental regulatory factors pathways, like exposure and costimulatory to Epstein-barr pathways virus, also silica contribute particles, alcohol, towards disease progressionand obesity [7]. The also environmental possesses the capabilityfactors like to exposure stimulate to suchEpstein-barr genetic loci.virus, The silica interaction particles, alcohol, andamong obesity these also genetic possesses and environmental the capability triggersto stimulate leads tosuch the genetic onset of loci. self-citrullinated The interaction among theseproteins, genetic which and form environmental autoantibodies triggers against leads citrullinated to the onset peptides. of self-citrullinated The exposure of the proteins, which formlungs autoantibodies to several exogenous against citrull compoundsinated peptides. like silica The particles, exposure Epstein-barr of the lungs virus, toAggregati- several exogenous bactercompounds actinomycetemcomitans like silica , andparticles,Porphyromonas Epstein-barr gingivalis virus,can triggerAggregatibacter the maturation of actinomycetemcomitansanti-citrullinated, and Porphyromonas protein-antibody gingivalis can (ACPA)trigger the and maturation citrullination of anti-citrullinated of self-proteins [8]. This protein-antibody (ACPA)citrullination and citrullination is catalyzed of self- via theproteins calcium-dependent [8]. This citrullination enzyme, is i.e.,catalyzed peptidylamine via the deami- nase (PAD4), which converts the cationic arginine into neutral but polar citrulline. In RA calcium-dependent enzyme, i.e., peptidylamine deaminase (PAD4), which converts the cationic patients, the PAD4 is secreted from the activated macrophages and granulocytes [9]. On the arginine into neutral but polar citrulline. In RA patients, the PAD4 is secreted from the activated other hand, the level of ACPA is increased in RA patients due to an abnormal response of macrophages and granulocytesthe immune [9]. system On the against other varioushand, the citrullinated level of ACPA proteins, is increased including in RA fibronectin, patients histones, due to an abnormal responsetype-II collagen, of the immune vimentin, system and ag fibrin.ainst Thesevarious compounds citrullinated also proteins, activate including the MHC-class II, fibronectin, histones,which type-II subsequently collagen, vimentin, stimulates and fibrin. the B-cells These to compounds produce further also activate ACPA. the This MHC- phase is also class II, which subsequentlyconsidered stimulates as the loss the of tolerance.B-cells to Anproduce interesting further thing ACPA. about This the ACPA phase is is that also the level of considered as the lossthese of tolerance. antibodies An is detected interesting years thing before about the the onset ACPA of RA is symptoms, that the level hence of earlythese detection antibodies is detectedand years prophylactic before the treatmentonset of RA of symptoms, these antibodies hence can early reduce detection the severity and prophylactic and progression of treatment of these antibodiesthe disease. can reduce the severity and progression of the disease. The visual illustrationThe of visualthe several illustration stages ofinvol theved several in the stages development involved of in RA the is development depicted in of RA is Figure 1 [10]. depicted in Figure1[10]. Figure 1. TheFigure visual 1. illustrationThe visual ofillustration the impact of of the several impact genetic of several and environmental genetic and factorsenvironmental in the pathogenesis factors in ofthe rheumatoid arthritis (RA).pathogenesis RF - rheumatoid of rheumatoid factor.
Load more

Recommended publications
  • First Insight Into Nutrition Effect on Spawning and Larvae Rearing of the Clam Ruditapes Decussatus L
    First insight into nutrition effect on spawning and larvae rearing of the clam Ruditapes decussatus L. from Dakhla Bay 1Yassine Ouagajjou, 2Touryia El Aloua, 3Mohamed El Moussaoui, 1El Mustafa Ait Chattou, 4Adil Aghzar, 3Younes Saoud 1 National Institute of Fisheries Research, INRH, Casablanca, Morocco; 2 Faculty of Science, Chouaib Doukkali University, El Jadida 24000, Morocco; 3 Faculty of Science, Abdelmalek Essaadi University, Tétouan 93002, Morocco; 4 Higher School of Technology, Sultan Moulay Slimane University, Khénifra, Morocco. Corresponding author: Y. Ouagajjou, [email protected]; [email protected] Abstract. The local clam Ruditapes decussatus has been a widespread bivalve along the natural beds in Dakhla Bay (Morocco). But, nowadays its overexploitation during many years has prompted the depletion of its occurrence in many extents and also has limited the availability of natural spat. In this study, the influence of nutrition on spawning, fertilization and larvae rearing was assessed for the first time. The potential of oocytes accumulation and release was highly influenced by the quality of microalgae combination (F = 20.7, p < 0.001) rather than their availability (F = 4.092, p < 0.05). Nevertheless, the eggs fertilization was also significantly affected by diet and ration respectively (F = 7.347, p < 0.01 and F = 4.645, p < 0.05). For larvae rearing, as regards to physiological responses, small size strains Isochrysis galbana and Pavlova lutheri are the most suitable regimen during early larvae phase, while diatom Chaetoceros calcitrans and large size strain Tetraselmis chui are more appropriate during late larvae phase. Therefore, the mixture of the four microalgae was the only diet that led to metamorphosis and settlement throughout this experiment.
    [Show full text]
  • The Anthelmintic Niclosamide Is a Potent TMEM16A Antagonist That Fully Bronchodilates Airways
    bioRxiv preprint doi: https://doi.org/10.1101/254888; this version posted January 27, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. The anthelmintic niclosamide is a potent TMEM16A antagonist that fully bronchodilates airways Kent Miner1, Benxian Liu1, Paul Wang2, Katja Labitzke2,†, Kevin Gaida1, Jian Jeffrey Chen3, Longbin Liu3,†, Anh Leith1,†, Robin Elliott1, Kathryn Henckels1, Esther Trueblood4,†, Kelly Hensley4, Xing-Zhong Xia1, Oliver Homann5, Brian Bennett1, Mike Fiorino1, John Whoriskey1, Sabine Escobar1, Gang Yu1, Joe McGivern2, Min Wong1, Teresa L. Born1,†, Alison Budelsky1,†, Mike Comeau1, Dirk Smith1,†, Jonathan Phillips1, James A. Johnston1, Kerstin Weikl2,†, David 2 1,* 2,†.* 1,† ,* Powers , Deanna Mohn , Andreas Hochheimer , John K. Sullivan 1Department of Inflammation Research, Amgen Inc., Thousand Oaks, CA and Seattle, WA, USA 2Department of Therapeutic Discovery, Amgen Inc., Thousand Oaks, CA, USA and Regensburg, Germany 3Department of Medicinal Chemistry, Amgen Inc., Thousand Oaks, CA, USA 4Department of Comparative Biology and Safety Sciences, Amgen Inc., Seattle, WA, Thousand Oaks, CA and South San Francisco, CA, USA 5Genome Analysis Unit, Amgen Inc., South San Francisco, CA, USA †Present address; see Additional Information section *Corresponding authors. E-mails: [email protected] (J.K.S); [email protected] (A.H.); [email protected] (D.M.) Abstract There is an unmet need in severe asthma where approximately 40% of patients exhibit poor -agonist responsiveness, suffer daily symptoms and show frequent exacerbations. 2+ Antagonists of the Ca -activated-Cl¯ channel, TMEM16A, offers a new mechanism to bronchodilate airways and block the multiple contractiles operating in severe disease.
    [Show full text]
  • Anthelmintic Activity of Yeast Particle-Encapsulated Terpenes
    molecules Article Anthelmintic Activity of Yeast Particle-Encapsulated Terpenes Zeynep Mirza 1, Ernesto R. Soto 1 , Yan Hu 1,2, Thanh-Thanh Nguyen 1, David Koch 1, Raffi V. Aroian 1 and Gary R. Ostroff 1,* 1 Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA; [email protected] (Z.M.); [email protected] (E.R.S.); [email protected] (Y.H.); [email protected] (T.-T.N.); [email protected] (D.K.); raffi[email protected] (R.V.A.) 2 Department of Biology, Worcester State University, Worcester, MA 01602, USA * Correspondence: gary.ostroff@umassmed.edu; Tel.: 508-856-1930 Academic Editor: Vaclav Vetvicka Received: 2 June 2020; Accepted: 24 June 2020; Published: 27 June 2020 Abstract: Soil-transmitted nematodes (STN) infect 1–2 billion of the poorest people worldwide. Only benzimidazoles are currently used in mass drug administration, with many instances of reduced activity. Terpenes are a class of compounds with anthelmintic activity. Thymol, a natural monoterpene phenol, was used to help eradicate hookworms in the U.S. South circa 1910. However, the use of terpenes as anthelmintics was discontinued because of adverse side effects associated with high doses and premature stomach absorption. Furthermore, the dose–response activity of specific terpenes against STNs has been understudied. Here we used hollow, porous yeast particles (YPs) to efficiently encapsulate (>95%) high levels of terpenes (52% w/w) and evaluated their anthelmintic activity on hookworms (Ancylostoma ceylanicum), a rodent parasite (Nippostrongylus brasiliensis), and whipworm (Trichuris muris). We identified YP–terpenes that were effective against all three parasites.
    [Show full text]
  • Antiparasitic Properties of Cardiovascular Agents Against Human Intravascular Parasite Schistosoma Mansoni
    pharmaceuticals Article Antiparasitic Properties of Cardiovascular Agents against Human Intravascular Parasite Schistosoma mansoni Raquel Porto 1, Ana C. Mengarda 1, Rayssa A. Cajas 1, Maria C. Salvadori 2 , Fernanda S. Teixeira 2 , Daniel D. R. Arcanjo 3 , Abolghasem Siyadatpanah 4, Maria de Lourdes Pereira 5 , Polrat Wilairatana 6,* and Josué de Moraes 1,* 1 Research Center for Neglected Diseases, Guarulhos University, Praça Tereza Cristina 229, São Paulo 07023-070, SP, Brazil; [email protected] (R.P.); [email protected] (A.C.M.); [email protected] (R.A.C.) 2 Institute of Physics, University of São Paulo, São Paulo 05508-060, SP, Brazil; [email protected] (M.C.S.); [email protected] (F.S.T.) 3 Department of Biophysics and Physiology, Federal University of Piaui, Teresina 64049-550, PI, Brazil; [email protected] 4 Ferdows School of Paramedical and Health, Birjand University of Medical Sciences, Birjand 9717853577, Iran; [email protected] 5 CICECO-Aveiro Institute of Materials & Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal; [email protected] 6 Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand * Correspondence: [email protected] (P.W.); [email protected] (J.d.M.) Citation: Porto, R.; Mengarda, A.C.; Abstract: The intravascular parasitic worm Schistosoma mansoni is a causative agent of schistosomiasis, Cajas, R.A.; Salvadori, M.C.; Teixeira, a disease of great global public health significance. Praziquantel is the only drug available to F.S.; Arcanjo, D.D.R.; Siyadatpanah, treat schistosomiasis and there is an urgent demand for new anthelmintic agents.
    [Show full text]
  • Antiprotozoal and Antitumor Activity of Natural Polycyclic Endoperoxides: Origin, Structures and Biological Activity
    molecules Review Antiprotozoal and Antitumor Activity of Natural Polycyclic Endoperoxides: Origin, Structures and Biological Activity Valery M. Dembitsky 1,2,*, Ekaterina Ermolenko 2, Nick Savidov 1, Tatyana A. Gloriozova 3 and Vladimir V. Poroikov 3 1 Centre for Applied Research, Innovation and Entrepreneurship, Lethbridge College, 3000 College Drive South, Lethbridge, AB T1K 1L6, Canada; [email protected] 2 A.V. Zhirmunsky National Scientific Center of Marine Biology, 17 Palchevsky Str., 690041 Vladivostok, Russia; [email protected] 3 Institute of Biomedical Chemistry, 10 Pogodinskaya Str., 119121 Moscow, Russia; [email protected] (T.A.G.); [email protected] (V.V.P.) * Correspondence: [email protected]; Tel.: +1-403-320-3202 (ext. 5463); Fax: +1-888-858-8517 Abstract: Polycyclic endoperoxides are rare natural metabolites found and isolated in plants, fungi, and marine invertebrates. The purpose of this review is a comparative analysis of the pharmacological potential of these natural products. According to PASS (Prediction of Activity Spectra for Substances) estimates, they are more likely to exhibit antiprotozoal and antitumor properties. Some of them are now widely used in clinical medicine. All polycyclic endoperoxides presented in this article demonstrate antiprotozoal activity and can be divided into three groups. The third group includes endoperoxides, which show weak antiprotozoal activity with a reliability of up to 70%, and this group includes only 1.1% of metabolites. The second group includes the largest number of endoperoxides, Citation: Dembitsky, V.M.; which are 65% and show average antiprotozoal activity with a confidence level of 70 to 90%. Lastly, Ermolenko, E.; Savidov, N.; the third group includes endoperoxides, which are 33.9% and show strong antiprotozoal activity with Gloriozova, T.A.; Poroikov, V.V.
    [Show full text]
  • Marine Pharmacology in 1999: Compounds with Antibacterial
    Comparative Biochemistry and Physiology Part C 132 (2002) 315–339 Review Marine pharmacology in 1999: compounds with antibacterial, anticoagulant, antifungal, anthelmintic, anti-inflammatory, antiplatelet, antiprotozoal and antiviral activities affecting the cardiovascular, endocrine, immune and nervous systems, and other miscellaneous mechanisms of action Alejandro M.S. Mayera, *, Mark T. Hamannb aDepartment of Pharmacology, Chicago College of Osteopathic Medicine, Midwestern University, 555 31st Street, Downers Grove, IL 60515, USA bSchool of Pharmacy, The University of Mississippi, Faser Hall University, MS 38677, USA Received 28 November 2001; received in revised form 30 May 2002; accepted 31 May 2002 Abstract This review, a sequel to the 1998 review, classifies 63 peer-reviewed articles on the basis of the reported preclinical pharmacological properties of marine chemicals derived from a diverse group of marine animals, algae, fungi and bacteria. In all, 21 marine chemicals demonstrated anthelmintic, antibacterial, anticoagulant, antifungal, antimalarial, antiplatelet, antituberculosis or antiviral activities. An additional 23 compounds had significant effects on the cardiovascular, sympathomimetic or the nervous system, as well as possessed anti-inflammatory, immunosuppressant or fibrinolytic effects. Finally, 22 marine compounds were reported to act on a variety of molecular targets, and thus could potentially contribute to several pharmacological classes. Thus, during 1999 pharmacological research with marine chemicals continued
    [Show full text]
  • Effects of Long-Acting, Broad Spectra Anthelmintic Treatments on The
    www.nature.com/scientificreports OPEN Efects of long‑acting, broad spectra anthelmintic treatments on the rumen microbial community compositions of grazing sheep Christina D. Moon1*, Luis Carvalho1, Michelle R. Kirk1, Alan F. McCulloch2, Sandra Kittelmann3, Wayne Young1, Peter H. Janssen1 & Dave M. Leathwick1 Anthelmintic treatment of adult ewes is widely practiced to remove parasite burdens in the expectation of increased ruminant productivity. However, the broad activity spectra of many anthelmintic compounds raises the possibility of impacts on the rumen microbiota. To investigate this, 300 grazing ewes were allocated to treatment groups that included a 100‑day controlled release capsule (CRC) containing albendazole and abamectin, a long‑acting moxidectin injection (LAI), and a non‑treated control group (CON). Rumen bacterial, archaeal and protozoal communities at day 0 were analysed to identify 36 sheep per treatment with similar starting compositions. Microbiota profles, including those for the rumen fungi, were then generated for the selected sheep at days 0, 35 and 77. The CRC treatment signifcantly impacted the archaeal community, and was associated with increased relative abundances of Methanobrevibacter ruminantium, Methanosphaera sp. ISO3‑F5, and Methanomassiliicoccaceae Group 12 sp. ISO4‑H5 compared to the control group. In contrast, the LAI treatment increased the relative abundances of members of the Veillonellaceae and resulted in minor changes to the bacterial and fungal communities by day 77. Overall, the anthelmintic treatments resulted in few, but highly signifcant, changes to the rumen microbiota composition. Anthelmintic treatment of adult ewes is practiced by about 80% of sheep farmers in New Zealand1, and many of these treatments use active compounds with broad-spectrum persistent activity.
    [Show full text]
  • Pathogens and Parasites of the Mussels Mytilus Galloprovincialis and Perna Canaliculus: Assessment of the Threats Faced by New Zealand Aquaculture
    Pathogens and Parasites of the Mussels Mytilus galloprovincialis and Perna canaliculus: Assessment of the Threats Faced by New Zealand Aquaculture Cawthron Report No. 1334 December 2007 EXECUTIVE SUMMARY The literature on pathogens and parasites of the mytilid genera Mytilus and Perna was surveyed with particular focus on M. galloprovincialis and P. canaliculus. Likely pathological threats posed to New Zealand mussel aquaculture were identified and recommendations were discussed under the following topics. Epidemiological differences between New Zealand Mytilus and Perna There is a paucity of data for this comparison. Comparability or otherwise would inform predictions as to the threat posed by overseas Mytilus parasites to New Zealand Perna and vice versa. Samples of P. canaliculus and M. galloprovincialis should be surveyed to establish any significant difference in parasite loads or pathology. Invasive dynamics and possible development of pathological threat The greatest potential threat to New Zealand Perna canaliculus aquaculture appears to be posed by parasites introduced by invading Mytilus species. These common ship-borne fouling organisms are a likely source of overseas pathogens, the most important of which are probably Marteilia spp. and disseminated haemic neoplasia. Hybridisation of invasive and local mussels presents a further potential pathology hazard by production of a more susceptible reservoir host thus giving the potential for production of more infected hosts and greater water load of transmission stages. Such an increase in transmission stages might be a cause of concern for Perna canaliculus whose susceptibility is currently unknown. Studies on Marteilia and haemic neoplasia are required to address the following questions: Is Perna canaliculus susceptible to either of these pathogens? What are the current prevalences of these pathogens in local mytilids? What species of mussels are entering New Zealand waters? Do they include Mytilus spp.
    [Show full text]
  • Identification of Pyrvinium, an Anthelmintic Drug, As a Novel Anti
    molecules Article Identification of Pyrvinium, an Anthelmintic Drug, as a Novel Anti-Adipogenic Compound Based on the Gene Expression Microarray and Connectivity Map Zonggui Wang 1, Zhong Dai 2,3, Zhicong Luo 2,3 and Changqing Zuo 2,3,* 1 Department of Biochemistry and Molecular Biology, Guangdong Medical University, Dongguan 523808, Guangdong, China 2 Guangdong Key Laboratory for Research and Development of Natural Drugs, Zhanjiang 524023, Guangdong, China 3 School of Pharmacy, Guangdong Medical University, Dongguan 523808, Guangdong, China * Correspondence: [email protected]; Tel.: +86-769-22896551 Received: 3 June 2019; Accepted: 27 June 2019; Published: 28 June 2019 Abstract: Obesity is a serious health problem, while the current anti-obesity drugs are not very effective. The Connectivity Map (C-Map), an in-silico drug screening approach based on gene expression profiles, has recently been indicated as a promising strategy for drug repositioning. In this study, we performed mRNA expression profile analysis using microarray technology and identified 435 differentially expressed genes (DEG) during adipogenesis in both C3H10T1/2 and 3T3-L1 cells. Then, DEG signature was uploaded into C-Map, and using pattern-matching methods we discovered that pyrvinium, a classical anthelminthic, is a novel anti-adipogenic differentiation agent. Pyrvinium suppressed adipogenic differentiation in a dose-dependent manner, as evidenced by Oil Red O staining and the mRNA levels of adipogenic markers. Furthermore, we identified that the inhibitory effect of pyrvinium was resulted primarily from the early stage of adipogenesis. Molecular studies showed that pyrvinium downregulated the expression of key transcription factors C/EBPa and PPARγ. The mRNA levels of notch target genes Hes1 and Hey1 were obviously reduced after pyrvinium treatment.
    [Show full text]
  • Parasiticides: Fenbendazole, Ivermectin, Moxidectin Livestock
    Parasiticides: Fenbendazole, Ivermectin, Moxidectin Livestock 1 Identification of Petitioned Substance* 2 3 Chemical Names: 48 Ivermectin: Heart Guard, Sklice, Stomectol, 4 Moxidectin:(1'R,2R,4Z,4'S,5S,6S,8'R,10'E,13'R,14'E 49 Ivomec, Mectizan, Ivexterm, Scabo 6 5 ,16'E,20'R,21'R,24'S)-21',24'-Dihydroxy-4 50 Thiabendazole: Mintezol, Tresaderm, Arbotect 6 (methoxyimino)-5,11',13',22'-tetramethyl-6-[(2E)- 51 Albendazole: Albenza 7 4-methyl-2-penten-2-yl]-3,4,5,6-tetrahydro-2'H- 52 Levamisole: Ergamisol 8 spiro[pyran-2,6'-[3,7,1 9]trioxatetracyclo 53 Morantel tartrate: Rumatel 9 [15.6.1.14,8.020,24] pentacosa[10,14,16,22] tetraen]- 54 Pyrantel: Banminth, Antiminth, Cobantril 10 2'-one; (2aE, 4E,5’R,6R,6’S,8E,11R,13S,- 55 Doramectin: Dectomax 11 15S,17aR,20R,20aR,20bS)-6’-[(E)-1,2-Dimethyl-1- 56 Eprinomectin: Ivomec, Longrange 12 butenyl]-5’,6,6’,7,10,11,14,15,17a,20,20a,20b- 57 Piperazine: Wazine, Pig Wormer 13 dodecahydro-20,20b-dihydroxy-5’6,8,19-tetra- 58 14 methylspiro[11,15-methano-2H,13H,17H- CAS Numbers: 113507-06-5; 15 furo[4,3,2-pq][2,6]benzodioxacylooctadecin-13,2’- Moxidectin: 16 [2H]pyrano]-4’,17(3’H)-dione,4’-(E)-(O- Fenbendazole: 43210-67-9; 70288-86-7 17 methyloxime) Ivermectin: 59 Thiabendazole: 148-79-8 18 Fenbendazole: methyl N-(6-phenylsulfanyl-1H- 60 Albendazole: 54965-21-8 19 benzimidazol-2-yl) carbamate 61 Levamisole: 14769-72-4 20 Ivermectin: 22,23-dihydroavermectin B1a +22,23- 21 dihydroavermectin B1b 62 Morantel tartrate: 26155-31-7 63 Pyrantel: 22204-24-6 22 Thiabendazole: 4-(1H-1,3-benzodiazol-2-yl)-1,3- 23 thiazole
    [Show full text]
  • WO 2018/117868 Al 28 June 2018 (28.06.2018) W !P O PCT
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2018/117868 Al 28 June 2018 (28.06.2018) W !P O PCT (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A23L 33/18 (2016.01) A61K 35/612 (2015.01) kind of national protection available): AE, AG, AL, AM, C12P 21/06 (2006.01) A61K 35/616 (2015.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, C12P 7/64 (2006 .0 1) A 61K 35/618 (2015.01) CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, A61K 35/00 (2006.01) DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, (21) International Application Number: KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, PCT/NZ20 17/050 167 MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (22) International Filing Date: OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, 20 December 2017 (20.12.2017) SC, SD, SE, SG, SK, SL, SM, ST, SV, SY,TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (25) Filing Language: English (84) Designated States (unless otherwise indicated, for every (26) Publication Language: English kind of regional protection available): ARIPO (BW, GH, (30) Priority Data: GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, 727786 20 December 2016 (20.12.2016) NZ UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, (71) Applicant: SANFORD LIMITED [NZ/NZ]; 22 Jellicoe EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, Street, Freemans Bay, Auckland, 1010 (NZ).
    [Show full text]
  • Impacts of the Invasive Ascidian Didemnum Vexillum on Green-Lipped Mussel Perna Canaliculus Aquaculture in New Zealand
    Vol. 4: 17–30, 2013 AQUACULTURE ENVIRONMENT INTERACTIONS Published online June 18 doi: 10.3354/aei00069 Aquacult Environ Interact OPENPEN ACCESSCCESS Impacts of the invasive ascidian Didemnum vexillum on green-lipped mussel Perna canaliculus aquaculture in New Zealand Lauren M. Fletcher1,2,*, Barrie M. Forrest1, James J. Bell2 1Cawthron Institute, Private Bag 2, Nelson 7010, New Zealand 2School of Biological Sciences, Victoria University of Wellington, PO Box 600, Wellington 6140, New Zealand ABSTRACT: Biofouling can pose a significant threat to shellfish aquaculture, as fouling organisms are often strong spatial competitors that are able to reach high densities or biomass in relatively short time frames. This study investigated the potential impacts of the colonial ascidian Didem- num vexillum on cultured New Zealand green-lipped mussels Perna canaliculus at one farm in the Marlborough Sounds region. Three size classes of mussels were examined: small (20 to 40 mm shell length at deployment), medium (40 to 60 mm), and large (60 to 70 mm). Replicate 4 m mussel lines were assigned to 1 of 3 treatments: (1) ambient fouling, (2) fouling enhanced by D. vexillum fragment inoculation (in addition to ambient fouling), or (3) control lines that were kept free of D. vexillum. After 15 mo, subsections of lines (0.5 m length) were processed to determine the effects of fouling cover on mussel density within lines, as well as on individual mussel size and condition. A highly significant negative relationship was shown between D. vexillum biomass and mussel density for small mussels, and to a lesser extent for medium mussels. Values of mussel condition indices were similar across size classes and across fouling treatments within each size class.
    [Show full text]