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Induction of cell death on Plasmodium falciparum asexual blood stages by Solanum nudum steroids
Authors:Mary Luz López  Rossiane Vommaro  Mariano Zalis  Wanderley de Souza  Silvia Blair  Cesar Segura
Institution:1. Grupo Malaria, Universidad de Antioquia, Sede de Investigación Universitaria-SIU, Medellín, Colombia;2. Laboratório de Ultraestrutura Celular Hertha Meyer, Universidade Federal do Rio de Janeiro. Rio de Janeiro, Brazil;3. Laboratório de Infectologia e Parasitologia Molecular, Universidade Federal do Rio de Janeiro. Rio de Janeiro, Brazil;1. Departamento de Ciências Farmacêuticas, Universidade Federal de Pernambuco, Brazil;2. Instituto de Ciências Exatas e Tecnologia, Universidade Federal do Amazonas, Brazil;3. Departamento de Antibióticos, Universidade Federal de Pernambuco, Brazil;1. School of Pharmaceutical Science, Yantai University, Yantai 264005, People''s Republic of China;2. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, People''s Republic of China;1. Departamento de Zootecnia, Faculdade de Ciências Agrárias e Veterinárias, UNESP-Univ Estadual Paulista, Jaboticabal, SP, Brasil;2. Departamento de Zootecnia, Escola de Medicina Veterinária e Zootecnia, Universidade Federal da Bahia, Salvador, BA, Brasil;3. Departamento de Ecologia, Zoologia e Genética, Universidade Federal de Pelotas, Pelotas, RS, Brasil;1. Institute of Chemistry, University of Tartu, Estonia;2. Department of Physiology, Institute of Biosciences, University of Sao Paulo, Brazil;3. Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom;4. Institut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris Descartes Cité Sorbonne, Paris, France;1. Research School of Biology, The Australian National University, Canberra, ACT 0200, Australia;2. Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia;3. Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA;4. Novartis Institute for Tropical Diseases (NITD), 138670 Singapore, Singapore;5. University of California, San Diego, School of Medicine, La Jolla, CA 92093, USA;1. Bioinformatics Division, School of Biosciences and Technology, Vellore, Institute of Technology University, Vellore, Tamil Nadu 632014, India;2. Cognizant Technology Solutions, Technocomplex, Plot GN-34/3, Sector-V, Saltlake Electronic Complex, Kolkata 700091, India
Abstract:Solanum nudum Dunal (Solanaceae) is a plant used in traditional medicine in Colombian Pacific Coast, from which five steroids denominated SNs have been isolated. The SNs compounds have antiplasmodial activity against asexual blood stages of Plasmodium falciparum strain 7G8 with an IC50 between 20–87 µM. However, their mode of action is unknown. Steroids regulate important cellular functions including cell growth, differentiation and death. Thus, the aim of this work was to determine the effects of S. nudum compounds on P. falciparum asexual blood stages and their association with cell death. We found that trophozoite and schizont stages were the most sensitive to SNs. By Giemsa-stained smears, induction of crisis forms was observed. Transmission electron microscopy of treated parasites showed morphological abnormalities such as a cytoplasm rich in vesicles and myelinic figures. The Mitochondria presented no morphological alterations and the nuclei showed no abnormal chromatin condensation. By the use of S. nudum compounds, cell death in P. falciparum was evident by a decrease in mitochondrial membrane potential, DNA fragmentation and cytoplasmic acidification. The asexual blood stages of P. falciparum showed some apoptotic-like and autophagic-like cell death characteristics induced by SNs treatment.
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