6-姜烯酚和葡甲胺锑酸盐对利什曼原虫的计算机和实验潜力:通过调节生物特性的多种协同组合。
In silico and experimental potentials of 6-shogaol and meglumine antimoniate on Leishmania major: multiple synergistic combinations through modulation of biological properties.
发表日期:2024 Aug 18
作者:
Saeid Shahsavari, Iraj Sharifi, Ehsan Salarkia, Alireza Keyhani, Fatemeh Sharifi, Zahra Babaei
来源:
CYTOKINE & GROWTH FACTOR REVIEWS
摘要:
常规治疗剂不再足以对抗利什曼病。这种复杂的情况仍然具有很高的死亡率和公共卫生影响。本研究旨在探索一系列广泛的实验来监测 6-姜烯酚(生姜的主要成分)和葡甲胺锑酸盐(MA 或 Glucantime®)的生物活性。 6-姜烯酚和诱导型一氧化氮合酶 (iNOS) 的结合亲和力是对接轮廓的来源,iNOS 是一种从 L-精氨酸催化一氧化氮 (NO) 的主要酶。使用比色法和巨噬细胞测定法评估 6-姜烯酚、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。通过可定量的实时聚合酶链式反应来测量可变表达的基因。通过流式细胞术分析细胞凋亡和细胞周期概况。此外,通过电泳进行DNA片段化分析,并通过酶联免疫吸附分析进行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-姜烯酚和 MA 表现出多种协同作用机制。这些包括显着的杀利什曼效应、有效的抗氧化活性、高安全指数、M1巨噬细胞/Th1相关细胞因子的上调(包括γ-干扰素、白细胞介素-12p40、肿瘤坏死因子-α和相关的iNOS)、显着的细胞分裂在亚 G0/G1 期捕获,通过核成分的 DNA 断裂而发生高调的细胞凋亡。此外,经过处理的细胞内无鞭毛体,NO 活性显着升高,而 SOD 和 CAT 活性显着降低。这项研究是排他性的,因为之前没有进行过类似的包容性调查。这些全面的机械作用为进一步的高级研究奠定了逻辑基础。© 2024。作者获得 Springer Science Business Media, LLC(Springer Nature 旗下公司)的独家许可。
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.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.