Department of Parasitology and Mycology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran.
PLoS Negl Trop Dis. 2020 Jan 13;14(1):e0007843. doi: 10.1371/journal.pntd.0007843. eCollection 2020 Jan.
BACKGROUND: Neglected parasitic diseases (NTDs) like cutaneous leishmaniasis (CL) have caused high mortality and morbidity rate in developing countries. This disease is considered as one of the six major tropical diseases, and has a great importance in HIV infected individuals as an opportunistic infection in those areas that both infections are endemic. This study evaluated the therapeutic effects of the Urtica dioica L (U. dioica) aqueous extract as an anti-leishmanial herbal drug in-vitro and in-vivo, and in addition to that, evaluated two vital immune system cytokines including gamma interferon (IFN-γ) and interleukin-4 (IL-4) plus nitric oxide (NO) and arginase activity against Leishmania major (L. major) infected mice. METHODOLOGY/PRINCIPAL FINDINGS: In-vitro anti-leishmanial activity of U. dioica aqueous extract was determined using MTT method and also Parasite Rescue Transformation Assay. Also, the footpad lesion size and parasite load in BALB/c mice infected with L. major were quantified for in-vivo assessment. Furthermore, for evaluating the immune responses, the levels of IFN-γ, IL-4, NO and arginase were measured in the BALB/c mice. These results indicated that U. dioica extract significantly reduced the L. major promastigotes viability. According to the in-vitro cytotoxicity assay of the extract on Leishmania parasites (CC50) and infected macrophages (EC50), the extract had no toxicity to the macrophages, however it efficiently killed the L. major amastigotes. In addition, the lesion size, parasite load, IL-4, and ARG were decreased in the treated infected mice, however IFN-γ and NO were significantly increased. CONCLUSIONS/SIGNIFICANCE: This study established satisfactory results in Leishmania parasite clearing both in-vivo and in-vitro. Therefore, U. dioica extract can be considered as an effective and harmless herbal compound for killing the parasite without toxicity to the host macrophages. Furthermore, it also can treat the CL by switching the mouse immune response towards a cell-mediated response (Th1); hence, it may be identified as a perfect therapeutic herbal drug for CL treatment.
背景:被忽视的寄生虫病(NTDs),如皮肤利什曼病(CL),在发展中国家造成了高死亡率和发病率。这种疾病被认为是六大热带病之一,在感染 HIV 的个体中具有重要意义,因为它是这些地区的机会性感染,这两种感染在这些地区都很流行。本研究评估了荨麻(U. dioica)水提取物作为一种抗利什曼草药药物在体外和体内的治疗效果,并评估了两种重要的免疫系统细胞因子,包括γ干扰素(IFN-γ)和白细胞介素 4(IL-4),外加一氧化氮(NO)和精氨酸酶活性对感染利什曼原虫(L. major)的小鼠的影响。
方法/主要发现:采用 MTT 法和寄生虫拯救转化试验测定荨麻水提取物的体外抗利什曼活性。还定量评估了 BALB/c 小鼠感染 L. major 后的足垫病变大小和寄生虫负荷。此外,为了评估免疫反应,测量了 BALB/c 小鼠的 IFN-γ、IL-4、NO 和精氨酸酶水平。结果表明,荨麻提取物显著降低了 L. major 前鞭毛体的活力。根据提取物对利什曼原虫(CC50)和感染巨噬细胞(EC50)的体外细胞毒性试验,提取物对巨噬细胞没有毒性,但能有效杀死 L. major 无鞭毛体。此外,治疗感染小鼠的病变大小、寄生虫负荷、IL-4 和 ARG 减少,而 IFN-γ 和 NO 显著增加。
结论/意义:本研究在体内和体外均对利什曼寄生虫的清除取得了令人满意的结果。因此,荨麻提取物可被视为一种有效且无害的草药化合物,可杀死寄生虫而不损害宿主巨噬细胞。此外,它还可以通过将小鼠免疫反应转向细胞介导反应(Th1)来治疗 CL,因此它可能被确定为治疗 CL 的理想治疗性草药药物。
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