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对感染 并用 治疗的小鼠的疟原虫血症、存活时间和促炎免疫反应的影响。

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

作者信息

Quadros Gomes Antônio Rafael, Castro Ana Laura Gadelha, Ferreira Gleison Gonçalves, Brígido Heliton Patrick Cordovil, Varela Everton Luiz Pompeu, Vale Valdicley Vieira, Carneiro Liliane Almeida, Dolabela Maria Fâni, Percario Sandro

机构信息

Postgraduate Program in Pharmaceutical Innovation, Federal University of Pará, Belém, Brazil.

Postgraduate Program in Biodiversity and Biotechnology, Federal University of Pará, Belém, Brazil.

出版信息

Front Pharmacol. 2024 Dec 5;15:1484934. doi: 10.3389/fphar.2024.1484934. eCollection 2024.

Abstract

studies with have demonstrated the antiparasitic activity of , attributed to its naphthoquinones. This study reports on pro-inflammatory changes in mice infected with and correlates these changes with parasitemia and survival. The ethanol extract of (EEEp) was fractionated under reflux to obtain the dichloromethane fraction (FDMEp) and isolated compounds from , relating these to survival time and parasitemia. Antimalarial activity was evaluated using the Peters suppressive test, with mice infected with and treated with , 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.

摘要

对[具体物质]的研究已证明其具有抗寄生虫活性,这归因于其萘醌类成分。本研究报告了感染[具体寄生虫]的小鼠体内的促炎变化,并将这些变化与寄生虫血症和存活率相关联。对[具体植物]的乙醇提取物(EEEp)进行回流分馏,得到二氯甲烷馏分(FDMEp),并从[具体植物]中分离出化合物,将其与存活时间和寄生虫血症相关联。使用彼得斯抑制试验评估抗疟活性,让感染[具体寄生虫]的小鼠用[具体物质]进行治疗,在30天内评估寄生虫血症和存活率。通过测量白细胞介素-10、干扰素-γ(IFN-γ)和一氧化氮水平来确定促炎特征。EEEp、FDMEp和刺五加醇在感染的第5天显示出活性,只有FDMEp在第8天仍有活性。用EEEp和FDMEp治疗可延长动物存活时间,降低IFN-γ和NO水平,并提高IL-10水平。刺五加醇显著改变了反应,刺五加醇葡萄糖醛酸苷似乎通过与乳酸脱氢酶结合而具有活性,抑制疟原虫色素代谢,导致寄生虫死亡。促炎变化似乎与存活和寄生虫血症降低无关。总之,FDMEp和刺五加醇降低了寄生虫血症,延长了存活时间,并调节了炎症反应。FDMEp和刺五加醇是开发新型抗疟药物的有前景的候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26e4/11656046/3a9df1d9ea46/fphar-15-1484934-g001.jpg

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