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Physalis angulata induces death of promastigotes and amastigotes of Leishmania (Leishmania) amazonensis via the generation of reactive oxygen species
Institution:1. Federal University of Pará, Institute of Biological Sciences, Laboratory of Parasitology and Laboratory of Structural Biology, Belém, Pará, Brazil;2. National Institute of Science and Technology in Structural Biology and Bioimaging, Rio de Janeiro, Rio de Janeiro, Brazil;3. Evandro Chagas Institute, Laboratory of Electron Microscopy, Department of Health Surveillance, Ministry of Health, Belém, Pará, Brazil;4. Federal University of Pará, Institute of Biological Sciences, Laboratory of Neurochemistry Molecular and Cellular, Belém, Pará, Brazil;1. Nano Material Research Laboratory, Department of Chemistry, Indian Institute of Technology (BHU), Varanasi 221005, U.P., India;2. Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701, USA;1. Institute of Marine Biology & Natural Products, Ocean College, Zhejiang University, Zijingang Campus, No. 866 Yuhangtang Road, Hangzhou 310058, PR China;2. Zhejiang Key Laboratory of Gastro-Intestinal Pathophysiology, Zhejiang Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, No. 54 Youdian Road, Hangzhou 310006, PR China;3. Zhejiang Institute for Drug Control, No. 86 Jichang Road, Hangzhou 310004, PR China;4. Zhejiang Provincial People''s Hospital, No. 158 Shangtang Rd., Hangzhou 310014, China;1. Depto. Botánica y Zoología, Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara, Km 15.5 Carr. Guadalajara-Nogales, Nextipac, Zapopan, Jalisco, CP 44100, Mexico;2. Depto. Ecología, Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara, Km 15.5 Carr. Guadalajara-Nogales, Zapopan, Jalisco, Mexico;3. Depto. Producción agrícola,Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara, Km 15.5 Carr. Guadalajara-Nogales, Zapopan, Jalisco, Mexico;1. Biological Sciences Department, State University of Feira de Santana, 44036-900 Feira de Santana, Bahia, Brazil;2. Department of Physics, Dr. Ambedkar Government Arts College, 600039 Chennai, Tamil Nadu, India;3. Agriculture and Forestry Engineering Department, Universidad de Valladolid, 34004 Palencia, Castilla y Leon, Spain;4. Superior Polytechnic School, European University Miguel de Cervantes, 47012 Valladolid, Castilla y Leon, Spain
Abstract:Leishmaniasis are a neglected group of emerging diseases that have been found in 98 countries and are caused by protozoa of the genus Leishmania. The therapy for leishmaniasis causes several side effects and leads to drug-resistant strains. Natural products from plants have exhibited activities against Leishmania in various experimental models. Physalis angulata is a widely used plant in popular medicine, and in the literature it has well-documented leishmanicidal activity. However, its mechanism of action is still unknown. Thus, this study aims to evaluate the mechanism driving the leishmanicidal activity of an aqueous extract of P. angulata root (AEPa). AEPa was effective against both promastigotes and intracellular amastigote forms of Leishmania amazonensis. This effect was mediated by an increase of reactive oxygen species (ROS), but not of nitric oxide (NO). The increased production of ROS induces cell death by phenotypes seems by apoptosis cell death in Leishmania, but not autophagy or necrosis. In addition, morphological analysis of macrophages showed that AEPa induced a high number of cytoplasmic projections, increased the volume of cytoplasm and number of vacuoles, caused cytoskeleton alterations and resulted in high spreading ability. AEPa also promoted superoxide anion (O2) production in both uninfected macrophages and those infected with Leishmania. Therefore, these results revealed that AEPa causes cell death by phenotypes seems by apoptosis cell death in L. amazonensis and modulates macrophage activation through morphofunctional alterations and O2 generation to induce Leishmania death.
Keywords:Antileishmanial activity  Macrophage activation  ROS production
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