is a major constraint in the development of small ruminant subsector due to significant production losses incurred by it. The present study explores the antiparasitic potential of three anthelmintic plants ( and ) against . taking albendazole as the standard. molecular docking and pharmacokinetic prediction studies were conducted with known bioactive molecules of these plants (palasonin, vinblastine, vincristine, betulinic acid and ursolic acid) against Glutamate Dehydrogenase (GDH) and tubulin molecules of the parasite. Methanolic extracts of these herbs were fractionated (hexane, ethyl acetate, chloroform and methanol) and used in larvicidal studies. Based on the data, two herbal prototypes were developed and clinically tested. All the 5 ligand molecules showed better binding affnity for GDH and tubulin protein as compared with albendazole and shared similar binding site in the core of the GDH hexamer with slight variations. Albendazole approximately stacked against GLY190A residue, showing hydrophobic interactions with PRO157A and a Pi-cation electrostatic interaction with ARG390 along with four hydrogen bonds. Vincristine formed 2 pi-anionic electrostatic bonds with ASP158 of B and C subunits alongwith hydrogen bonding and hydrophobic interaction and an additional pi-anion electrostatic interaction at ASP158A for vinblastine. Albendazole bound to α-tubulin next to colchicine site whereas vinblastine is bound at the nearby laulimalide/peloruside site of the dimer. Betulinic acid showed lateral interaction between the H2-H3 loop of one alpha subunit and H10 of the adjacent alpha subunit of two tubulin dimers. Ursolic acid and palasonin bound at the intradimer N site of microtubulin involving the H1-H7 and H1-H2 zone, respectively. The studies demonstrated good dose dependent anthelmintic potential. Both the prototypes were quite efficacious in clearing the infection, keeping it to a minimal for more than 5 months, probably, through direct anthelmintic effect through GDH, tubulin depolymerization and uncoupling as well as indirectly through immunomodulation along with antioxidant and anti-inflammatory properties.
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http://dx.doi.org/10.1016/j.heliyon.2022.e08789 | DOI Listing |
Heliyon
January 2022
Division of Animal Health, ICAR-Central Institute for Research on Goats, Makhdoom, Farah, Mathura, 281122, UP, India.
is a major constraint in the development of small ruminant subsector due to significant production losses incurred by it. The present study explores the antiparasitic potential of three anthelmintic plants ( and ) against . taking albendazole as the standard.
View Article and Find Full Text PDFMicrob Pathog
December 2020
Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Medical Lab Technology, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Iran. Electronic address:
Leishmaniasis is an infectious disease caused by Leishmania that widespread in 98 countries. The differentiation of Leishmania (L) from procyclic to metacyclic promastigote has occurred along with morphological and biochemical changes in proteome scale. We aim here to identify the proteomes of two successive developmental forms (procyclic and metacyclic promastigotes) from Leishmania major isolates using SWATH-MS quantitative proteomics technique.
View Article and Find Full Text PDFProtein Sci
August 2019
Department of Chemistry & Biochemistry, University of San Diego, San Diego, California, 92110.
Suppressor of IKKepsilon (SIKE) is a 207 residue protein that is implicated in the TLR3-TANK-binding kinase-1-mediated response to viral infection. SIKE's function in this pathway is unknown, but SIKE forms interactions with two distinct cytoskeletal proteins, α-actinin and tubulin, and SIKE knockout reduces cell migration. As structure informs function and in the absence of solved structural homologs, our studies were directed toward creating a structural model of SIKE through biochemical and biophysical characterization to probe and interrogate SIKE function.
View Article and Find Full Text PDFBiology (Basel)
December 2016
Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 19991, Russia.
J Am Chem Soc
July 2010
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14850, USA.
Poly(ADP-ribose) polymerases (PARPs) catalyze the transfer of multiple adenine diphosphate ribose (ADP-ribose) units from nicotinamide adenine dinucleotide (NAD) to substrate proteins. There are 17 PARPs in humans. Several PARPs, such as PARP-1 and Tankyrase-1, are known to play important roles in DNA repair, transcription, mitosis, and telomere length maintenance.
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