In silico and experimental potentials of 6-shogaol and meglumine antimoniate on Leishmania major: multiple synergistic combinations through modulation of biological properties.

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC
Saeid Shahsavari, Iraj Sharifi, Ehsan Salarkia, Alireza Keyhani, Fatemeh Sharifi, Zahra Babaei
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引用次数: 0

Abstract

Conventional therapeutic agents are no longer adequate against leishmaniasis. This complex condition continues to have a high mortality rate and public health impact. The present study aimed to explore an extensive array of experiments to monitor the biological activities of 6-shogaol, a major component of ginger, and meglumine antimoniate (MA or Glucantime®). The binding affinity of 6-shogaol and inducible nitric oxide synthase (iNOS), a major enzyme catalyzing nitric oxide (NO) from L-arginine was the source for the docking outline. The inhibitory effects of 6-shogaol, MA, and mixture were assessed using colorimetric and macrophage assays. Antioxidant activity was inferred by UV-visible spectrophotometry. Variably expressed genes were measured by quantifiable real-time polymerase chain reaction. Apoptotic and cell cycle profiles were analyzed by flow cytometry. Moreover, a DNA fragmentation assay was performed by electrophoresis and antioxidant metabolites include superoxide dismutase (SOD), catalase (CAT), and also nitric oxide (NO) by enzyme-linked immunosorbent assay. 6-shogaol and MA exhibited multiple synergistic mechanisms of action. These included a remarkable leishmanicidal effect, potent antioxidative activity, a high safety index, upregulation of M1 macrophages/Th1-associated cytokines (including, γ-interferon, interleukin-12p40, tumor necrotizing factor-alpha, and associated iNOS), significant cell division capture at the sub-G0/G1 phase, a high profile of apoptosis through DNA fragmentation of the nuclear components. In addition, the activity of NO was substantially elevated by treated intracellular amastigotes, while SOD and CAT activities were significantly diminished. This study is exclusive because no similar investigation has inclusively been conducted before. These comprehensive mechanistic actions form a logical foundation for additional advanced study.

Abstract Image

6-shogaol 和 meglumine antimoniate 对利什曼原虫的硅学和实验潜力:通过调节生物特性实现多重协同组合。
传统的利什曼病治疗药物已不再适用。这种复杂的疾病仍然具有很高的死亡率和对公共健康的影响。本研究旨在探索一系列广泛的实验,以监测生姜的主要成分 6-肖高醇和巨鲁明抗锑酸盐(MA 或 Glucantime®)的生物活性。对接大纲以 6-肖高醇与诱导型一氧化氮合酶(iNOS)(一种从 L-精氨酸催化一氧化氮(NO)的主要酶)的结合亲和力为依据。使用比色法和巨噬细胞法评估了 6-shogaol、MA 和混合物的抑制作用。通过紫外可见分光光度法推断抗氧化活性。可变表达基因通过可量化的实时聚合酶链反应进行测量。流式细胞术分析了细胞凋亡和细胞周期情况。此外,还采用电泳法进行了 DNA 片段分析,并采用酶联免疫吸附法测定了抗氧化代谢物,包括超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和一氧化氮(NO)。6-shogaol 和 MA 表现出多种协同作用机制。这些机制包括显著的杀利什曼作用、强效抗氧化活性、高安全指数、上调 M1 巨噬细胞/Th1 相关细胞因子(包括γ-干扰素、白细胞介素-12p40、肿瘤坏死因子-α 和相关 iNOS)、在亚 G0/G1 阶段显著捕获细胞分裂、通过核成分的 DNA 断裂实现细胞凋亡。此外,经处理的细胞内母细胞的 NO 活性大幅提高,而 SOD 和 CAT 活性则显著降低。这项研究具有独创性,因为此前从未进行过类似的综合调查。这些全面的机理作用为进一步的深入研究奠定了合理的基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.20
自引率
4.30%
发文量
567
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