In Vitro and In Vivo Leishmanicidal Activity of Beauvericin.

IF 3.3 2区 生物学 Q2 CHEMISTRY, MEDICINAL
Journal of Natural Products Pub Date : 2024-12-27 Epub Date: 2024-12-03 DOI:10.1021/acs.jnatprod.4c01098
Virlânio A de Oliveira Filho, Juliana R Gubiani, Vitória D Borgonovi, Felipe Hilário, Marcelo R de Amorim, Karen Minori, Vitor K S Bertolini, Antonio G Ferreira, Andressa R Biz, Marcos A Soares, Helder L Teles, Fernanda R Gadelha, Roberto G S Berlinck, Danilo C Miguel
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引用次数: 0

Abstract

Leishmaniasis is a worldwide disease caused by more than 20 species of Leishmania parasites. Leishmania amazonensis and L. braziliensis are among the main causative agents of cutaneous leishmaniasis, presenting a broad spectrum of clinical forms. As these pathologies lead to unsatisfactory treatment outcomes, the discovery of alternative chemotherapeutic options is urgently required. In this investigation, a leishmanicidal bioassay-guided fractionation of the growth media extract produced by Aspergillus terreus P63 led to the isolation of the cyclic depsipeptide beauvericin (1). The viability of L. amazonensis, L. braziliensis and mammalian cells (macrophages and L929 fibroblasts) was assessed in 1 incubated cultures. Leishmania promastigotes were sensitive to 1, with EC50 values ranging from 0.7 to 1.3 μM. Microscopy analysis indicated that Leishmania spp. parasites showed morphological abnormalities in a dose-dependent manner in the presence of 1. L. amazonensis intracellular amastigotes were more sensitive to 1 than promastigotes (EC50 = 0.8 ± 0.1 μM), with a good selectivity index (22-30). 1 reduced the infectivity index at very low concentrations, maintaining the integrity of the primary murine host cell for up to the highest concentration tested for 1. In vivo assays of 1 conducted using BALB/c mice infected with stationary-phase promastigotes of L. amazonensis in the tail base presented a significant reduction in the lesion parasite load. A second round of in vivo assays was performed to assess the efficacy of the topical use of 1. The results demonstrated a significant decrease in the total ulcerated area of mice treated with 1 when compared with untreated animals. Our results present promising in vitro and in vivo leishmanicidal effects of beauvericin, emphasizing that systemic inoculation of 1 led to a decrease in the parasite load at the lesion site, whereas topical administration of 1 delayed the progression of leishmaniasis ulcers, a cure criterion established for cutaneous leishmaniasis management.

Beauvericin体外和体内杀灭利什曼尼菌活性研究。
利什曼病是一种由20多种利什曼原虫引起的世界性疾病。亚马逊利什曼原虫和巴西利什曼原虫是皮肤利什曼病的主要病原体,表现出广泛的临床形式。由于这些病理导致治疗效果不理想,因此迫切需要发现替代化疗方案。在这项研究中,用利什曼尼法指导对土曲霉P63产生的生长培养基提取物进行分离,分离出环沉积肽beauvericin(1)。在1个培养物中评估了亚马逊乳杆菌、巴西乳杆菌和哺乳动物细胞(巨噬细胞和L929成纤维细胞)的活力。promastigotes利什曼原虫对1敏感,EC50值在0.7 ~ 1.3 μM之间。镜检分析表明,利什曼原虫在1。amazon L. amazonensis胞内无性系对1的敏感性高于promastigotes (EC50 = 0.8±0.1 μM),具有良好的选择性指数(22 ~ 30)。1在极低浓度下降低感染性指数,维持原代小鼠宿主细胞的完整性,直至1测试的最高浓度。在BALB/c小鼠的体内实验中,在尾基感染了亚马逊河猴静止期原毛菌,结果显示,病变部位的寄生虫负荷显著降低。进行第二轮体内试验以评估局部使用1的疗效。结果表明,与未治疗的动物相比,1治疗小鼠的总溃疡面积显着减少。我们的研究结果显示了beauvericin体外和体内杀灭利什曼原虫的良好效果,强调全身接种1可减少病变部位的寄生虫负荷,而局部给药1可延缓利什曼病溃疡的进展,这是皮肤利什曼病治疗的治愈标准。
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来源期刊
CiteScore
9.10
自引率
5.90%
发文量
294
审稿时长
2.3 months
期刊介绍: The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin. When new compounds are reported, manuscripts describing their biological activity are much preferred. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.
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