دورية أكاديمية
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Curzerene antileishmania activity: Effects on Leishmania amazonensis and possible action mechanisms.

التفاصيل البيبلوغرافية
العنوان: Curzerene antileishmania activity: Effects on Leishmania amazonensis and possible action mechanisms.
المؤلفون: Nunes TAL; Laboratório de Doenças Infecciosas, Campus Ministro Reis Velloso, Universidade Federal do Delta do Parnaíba, 64202-020 Parnaíba, PI, Brazil., Santos MM; Laboratório de Imunologia e Parasitologia, Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro, 38025-180 Uberaba, MG, Brazil., de Oliveira MS; Laboratório de Imunologia e Parasitologia, Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro, 38025-180 Uberaba, MG, Brazil., de Sousa JMS; Laboratório de Doenças Infecciosas, Campus Ministro Reis Velloso, Universidade Federal do Delta do Parnaíba, 64202-020 Parnaíba, PI, Brazil., Rodrigues RRL; Laboratório de Doenças Infecciosas, Campus Ministro Reis Velloso, Universidade Federal do Delta do Parnaíba, 64202-020 Parnaíba, PI, Brazil., Sousa PSA; Núcleo de Pesquisa em Biotecnologia e Biodiversidade, Campus Ministro Reis Velloso, Universidade Federal do Delta do Parnaíba, 64202-020 Parnaíba, PI, Brazil., de Araújo AR; Núcleo de Pesquisa em Biotecnologia e Biodiversidade, Campus Ministro Reis Velloso, Universidade Federal do Delta do Parnaíba, 64202-020 Parnaíba, PI, Brazil., Pereira ACTDC; Laboratório de Biologia de Microrganismos, Campus Ministro Reis Velloso, Universidade Federal do Delta do Parnaíba, 64202-020 Parnaíba, PI, Brazil., Ferreira GP; Laboratório de Biologia de Microrganismos, Campus Ministro Reis Velloso, Universidade Federal do Delta do Parnaíba, 64202-020 Parnaíba, PI, Brazil., Rocha JA; Grupo de Pesquisa em Química Medicinal e Biotecnologia, QUIMEBIO, Universidade Federal do Maranhão, UFMA, São Bernardo, MA, Brazil., Rodrigues Junior V; Laboratório de Imunologia e Parasitologia, Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro, 38025-180 Uberaba, MG, Brazil., da Silva MV; Laboratório de Imunologia e Parasitologia, Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro, 38025-180 Uberaba, MG, Brazil., Rodrigues KADF; Laboratório de Doenças Infecciosas, Campus Ministro Reis Velloso, Universidade Federal do Delta do Parnaíba, 64202-020 Parnaíba, PI, Brazil. Electronic address: klinger@ufpi.edu.br.
المصدر: International immunopharmacology [Int Immunopharmacol] 2021 Nov; Vol. 100, pp. 108130. Date of Electronic Publication: 2021 Sep 06.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 100965259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1705 (Electronic) Linking ISSN: 15675769 NLM ISO Abbreviation: Int Immunopharmacol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Amsterdam ; New York : Elsevier Science, c2001-
مواضيع طبية MeSH: Antiprotozoal Agents/*pharmacology , Leishmania mexicana/*drug effects , Sesquiterpenes/*pharmacology, Animals ; Antiprotozoal Agents/therapeutic use ; Apoptosis/drug effects ; Humans ; Interferon-gamma/metabolism ; Interleukin-10/metabolism ; Interleukin-12/metabolism ; Interleukin-6/metabolism ; Leishmania mexicana/growth & development ; Macrophages/drug effects ; Mice ; Mice, Transgenic ; Molecular Docking Simulation ; RAW 264.7 Cells ; Tumor Necrosis Factor-alpha/metabolism
مستخلص: Leishmaniasis is a set of infectious diseases with high rates of morbidity and mortality, it affects millions of people around the world. Treatment, mainly with pentavalent antimonials, presents significant toxicity and many cases of resistance. In previous works we have demonstrated the effective and selective antileishmanial activity of Eugenia uniflora L. essential oil, being constituted (47.3%) by the sesquiterpene curzerene. Considering the high rate of parasite inhibition demonstrated for E. uniflora essential oil, and the significant presence of curzerene in the oil, this study aimed to evaluate its antileishmania activity and possible mechanisms of action. Curzerene was effective in inhibiting the growth of promastigotes (IC 50 3.09 ± 0.14 µM) and axenic amastigotes (EC 50 2.56 ± 0.12 µM), with low cytotoxicity to RAW 264.7 macrophages (CC 50 83.87 ± 4.63 µM). It was observed that curzerene has direct effects on the parasite, inducing cell death by apoptosis with secondary necrotic effects (producing pores in the plasma membrane). Curzerene proved to be even more effective against intra-macrophage amastigote forms, with an EC 50 of 0.46 ± 0.02 µM. The selectivity index demonstrated by curzerene on these parasite forms was 182.32, being respectively 44.15 and 8.47 times more selective than meglumine antimoniate and amphotericin B. The antiamastigote activity of curzerene was associated with immunomodulatory activity, as it increased TNF-α, IL-12, and NO levels, and lysosomal activity, and decreased IL-10 and IL-6 cytokine levels detected in macrophages infected and treated. In conclusion, our results demonstrate that curzerene is an effective and selective antileishmanial agent, a candidate for in vivo investigation in models of antileishmanial activity.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: Antileishmania; Curzerene; L. amazonensis
المشرفين على المادة: 0 (Antiprotozoal Agents)
0 (Interleukin-6)
0 (Sesquiterpenes)
0 (Tumor Necrosis Factor-alpha)
0 (curzerene)
130068-27-8 (Interleukin-10)
187348-17-0 (Interleukin-12)
82115-62-6 (Interferon-gamma)
تواريخ الأحداث: Date Created: 20210909 Date Completed: 20220221 Latest Revision: 20220221
رمز التحديث: 20240829
DOI: 10.1016/j.intimp.2021.108130
PMID: 34500286
قاعدة البيانات: MEDLINE
الوصف
تدمد:1878-1705
DOI:10.1016/j.intimp.2021.108130