Impact on parasitemia, survival time and pro-inflammatory immune response in mice infected with Plasmodium berghei treated with Eleutherine plicata.

IF 4.8 2区 医学 Q1 PHARMACOLOGY & PHARMACY Frontiers in Pharmacology Pub Date : 2024-12-05 eCollection Date: 2024-01-01 DOI:10.3389/fphar.2024.1484934
Antônio Rafael Quadros Gomes, Ana Laura Gadelha Castro, Gleison Gonçalves Ferreira, Heliton Patrick Cordovil Brígido, Everton Luiz Pompeu Varela, Valdicley Vieira Vale, Liliane Almeida Carneiro, Maria Fâni Dolabela, Sandro Percario
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Abstract

In vitro studies with Plasmodium falciparum have demonstrated the antiparasitic activity of E. plicata, attributed to its naphthoquinones. This study reports on pro-inflammatory changes in mice infected with P. berghei and correlates these changes with parasitemia and survival. The ethanol extract of Eleutherine plicata (EEEp) was fractionated under reflux to obtain the dichloromethane fraction (FDMEp) and isolated compounds from E. plicata, relating these to survival time and parasitemia. Antimalarial activity was evaluated using the Peters suppressive test, with mice infected with Plasmodium berghei and treated with E. plicata, assessing parasitemia and survival over 30 days. The pro-inflammatory profile was determined by measuring interleukin-10, interferon-γ (IFN-γ), and nitric oxide levels. EEEp, FDMEp, and eleutherol showed activity on the 5th day of infection, with only FDMEp being active on the 8th day. Treatment with EEEp and FDMEp extended animal survival, reduced IFN-γ and NO levels, and increased IL-10 levels. Eleutherol significantly altered the response, with eleutherol glucuronide seemingly active by binding to lactate dehydrogenase, inhibiting hemozoin metabolism, leading to parasite death. Pro-inflammatory changes did not appear to correlate with survival and reduced parasitemia. In summary, FDMEp and eleutherol reduced parasitemia, extended survival, and modulated the inflammatory response. FDMEp and eleutherol are promising candidates for developing new antimalarial drugs.

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细叶莲子对伯氏疟原虫感染小鼠寄生虫血症、存活时间和促炎免疫反应的影响。
对恶性疟原虫的体外研究表明,E. plicata 具有抗寄生虫活性,这归功于其萘醌类物质。本研究报告了小鼠感染 P. berghei 后的促炎变化,并将这些变化与寄生虫血症和存活率联系起来。在回流条件下对荸荠乙醇提取物(EEEp)进行分馏,得到二氯甲烷馏分(FDMEp),并从荸荠中分离出化合物,将其与存活时间和寄生虫血症联系起来。使用彼得斯抑制试验评估抗疟活性,小鼠感染疟原虫后,用 E. plicata 治疗,评估寄生虫血症和 30 天的存活率。通过测量白细胞介素-10、干扰素-γ(IFN-γ)和一氧化氮的水平来确定促炎特征。EEEp、FDMEp和榄香素在感染的第5天显示出活性,只有FDMEp在第8天显示出活性。使用EEEp和FDMEp可延长动物存活时间,降低IFN-γ和一氧化氮水平,提高IL-10水平。榄香烯醇明显改变了反应,榄香烯醇葡萄糖醛酸苷似乎通过与乳酸脱氢酶结合而发挥活性,抑制造血素代谢,导致寄生虫死亡。促炎性变化似乎与存活率和寄生虫血症的降低无关。总之,FDMEp 和 Eleutherol 可降低寄生虫血症、延长存活时间并调节炎症反应。FDMEp和榄香烯醇是开发新型抗疟药物的理想候选药物。
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来源期刊
Frontiers in Pharmacology
Frontiers in Pharmacology PHARMACOLOGY & PHARMACY-
CiteScore
7.80
自引率
8.90%
发文量
5163
审稿时长
14 weeks
期刊介绍: Frontiers in Pharmacology is a leading journal in its field, publishing rigorously peer-reviewed research across disciplines, including basic and clinical pharmacology, medicinal chemistry, pharmacy and toxicology. Field Chief Editor Heike Wulff at UC Davis is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
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