Antileishmania, Immune Modulation and Apoptosis Induction by Astragalus ecbatanus Extract Against Leishmania tropica

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-06-11 DOI:10.5812/jjnpp-146164

Hossein Mahmoudvand, Amal Khudair Khalaf, Leila Masoori, Javad Ghasemian Yadegari

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引用次数: 0

Abstract

Background: Due to the unique properties of Astragalus in treating diseases and strengthening the immune system, this study aimed to investigate, for the first time, the immune modulation and apoptosis induction by Astragalus ecbatanus extract against Leishmania tropica. Methods: The study assessed the in vitro efficacy of the Astragalus ecbatanus extract against both the promastigote and amastigote stages of L. tropica (MHOM/AF/88/KK27). Additionally, the effects of the extract on inducing nitric oxide (NO) release and its cytotoxicity on human macrophage cells were determined by calculating the 50% cytotoxic concentrations (CC50). The study also evaluated the Caspase-3-like activity in extract-treated parasites and conducted quantitative real-time PCR to assess the expression of genes associated with T lymphocytes. Results: Our study demonstrated that the A. ecbatanus extract significantly (P < 0.001) decreased the viability of both L. tropica promastigote and amastigote forms compared to the negative control. Moreover, the extract exhibited a high selectivity index (> 10), indicating its strong specificity towards intracellular parasites while showing low cytotoxicity to host cells. Our results indicated a dose-dependent upregulation of the expression levels of genes for inducible nitric oxide synthase (iNOS), interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNFα), and interleukin-10 (IL-10) in macrophages after exposure to A. ecbatanus ethyl acetate extract (P < 0.01). In contrast, the gene expression level of IL-10 exhibited a dose-dependent downregulation after exposure to A. ecbatanus ethyl acetate extract. We also found that the THP-1 macrophages exposed to the A. ecbatanus ethyl acetate extract exhibited enhanced production of nitric oxide (P < 0.001). Additionally, the ethyl acetate extract of A. ecbatanus significantly enhanced caspase-3 activation in Leishmania parasites (P < 0.01). Conclusions: The results demonstrated the significant impact of A. ecbatanus ethyl acetate extract on inhibiting and eradicating Leishmania parasites in laboratory settings. While some cellular mechanisms of action were identified, such as immune modulation and apoptosis induction against Leishmania parasites, further investigation is essential to elucidate the specific mechanisms of action and assess the efficacy in animal and human populations.

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黄芪提取物对热带利什曼原虫的抗利什曼病、免疫调节和细胞凋亡诱导作用

背景：鉴于黄芪在治疗疾病和增强免疫系统方面的独特功效，本研究旨在首次探讨黄芪提取物对热带利什曼病的免疫调节和细胞凋亡诱导作用。研究方法本研究评估了黄芪提取物对热带利什曼原虫和非原虫阶段（MHOM/AF/88/KK27）的体外疗效。此外，通过计算 50%的细胞毒性浓度（CC50），确定了黄芪提取物诱导一氧化氮（NO）释放的效果及其对人巨噬细胞的细胞毒性。研究还评估了萃取物处理过的寄生虫的类 Caspase-3 活性，并通过实时定量 PCR 评估了与 T 淋巴细胞相关的基因的表达。结果我们的研究表明，与阴性对照组相比，A. ecbatanus 提取物能显著降低 L. tropica 原原体和非原体的存活率（P < 0.001）。此外，该提取物还表现出很高的选择性指数（> 10），表明它对细胞内寄生虫具有很强的特异性，同时对宿主细胞的细胞毒性很低。我们的研究结果表明，暴露于 A. ecbatanus 乙酸乙酯提取物后，巨噬细胞中诱导型一氧化氮合酶（iNOS）、γ 干扰素（IFN-γ）、肿瘤坏死因子-α（TNFα）和白细胞介素-10（IL-10）基因的表达水平呈剂量依赖性上调（P < 0.01）。相反，IL-10的基因表达水平在暴露于蜕皮激素乙酸乙酯提取物后表现出剂量依赖性下调。我们还发现，THP-1 巨噬细胞暴露于蜕皮激素乙酸乙酯提取物后，一氧化氮的产生量增加（P < 0.001）。此外，信天翁乙酸乙酯萃取物还能显著增强利什曼寄生虫体内 Caspase-3 的活化（P < 0.01）。结论研究结果表明，A. ecbatanus 乙酸乙酯提取物对抑制和消灭实验室环境中的利什曼原虫寄生虫有重大影响。虽然确定了一些细胞作用机制，如免疫调节和诱导利什曼病寄生虫凋亡，但要阐明具体的作用机制并评估其在动物和人类群体中的功效，还需要进一步的研究。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.