Laboratory of Immunopathology, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, 38400-902, Minas Gerais, Brazil.
Institute of Exact and Natural Sciences, Federal University of Mato Grosso, Rondonópolis, 78735-901, Mato Grosso, Brazil.
Sci Rep. 2018 Jan 24;8(1):1547. doi: 10.1038/s41598-018-19840-x.
Increased resistance to the first-line treatment against P. falciparum malaria, artemisinin-based combination therapies, has been reported. Here, we tested the effect of crude ethanolic extract of the fungus Trichoderma stromaticum (Ext-Ts) on the growth of P. falciparum NF54 in infected human red blood cells (ihRBCs) and its anti-malarial and anti-inflammatory properties in a mouse model of experimental cerebral malaria. For this purpose, ihRBCs were treated with Ext-Ts and analysed for parasitaemia; C57BL/6 mice were infected with P. berghei ANKA (PbA), treated daily with Ext-Ts, and clinical, biochemical, histological and immunological features of the disease were monitored. It was observed that Ext-Ts presented a dose-dependent ability to control P. falciparum in ihRBCs. In addition, it was demonstrated that Ext-Ts treatment of PbA-infected mice was able to increase survival, prevent neurological signs and decrease parasitaemia at the beginning of infection. These effects were associated with systemically decreased levels of lipids and IFN-γ, ICAM-1, VCAM-1 and CCR5 cerebral expression, preserving blood brain barrier integrity and attenuating the inflammatory lesions in the brain, liver and lungs. These results suggest that Ext-Ts could be a source of immunomodulatory and antimalarial compounds that could improve the treatment of cerebral malaria.
已经报道了对青蒿素为基础的联合疗法(一线抗疟药物)的耐药性增加。在这里,我们测试了真菌 Trichoderma stromaticum 的粗乙醇提取物(Ext-Ts)对感染人类红细胞(ihRBC)中的 P. falciparum NF54 生长的影响,以及在实验性脑疟小鼠模型中的抗疟和抗炎特性。为此,用 Ext-Ts 处理 ihRBC 并分析寄生虫血症;用 P. berghei ANKA(PbA)感染 C57BL/6 小鼠,每天用 Ext-Ts 治疗,并监测疾病的临床、生化、组织学和免疫学特征。结果表明,Ext-Ts 具有剂量依赖性控制 ihRBC 中 P. falciparum 的能力。此外,还证明了 Ext-Ts 治疗 PbA 感染小鼠能够提高存活率,预防感染初期的神经症状和降低寄生虫血症。这些作用与系统性降低脂质和 IFN-γ、ICAM-1、VCAM-1 和 CCR5 脑表达水平相关,维持血脑屏障的完整性,并减轻脑、肝和肺中的炎症损伤。这些结果表明,Ext-Ts 可能是免疫调节和抗疟化合物的来源,可改善脑疟的治疗。