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单独使用和与阿托伐醌联合使用蜂王酸(10-羟基-2-癸烯酸)的体外抗疟效果和诱导凋亡作用。

In vitro anti- effects and apoptotic induction of queen bee acid (10-hydroxy-2-decenoic acid) alone and in combination with atovaquone.

机构信息

Faculty of Pharmacy, Eastern Mediterranean University, Famagusta, North Cyprus.

出版信息

Arch Razi Inst. 2024 Apr 30;79(2):321-326. doi: 10.32592/ARI.2024.79.2.321. eCollection 2024 Apr.

Abstract

Toxoplasmosis, which is caused by the parasite, is a parasitic, infectious disease. 10-hydroxy-2-decenoic acid (10-H2DA, queen bee acid (QBA), is one of the most prevalent fatty acids (>40%) present in royal jelly. Studies have pointed to antitumor, anti-inflammatory, antiangiogenic, and antimicrobial effects of 10-H2DA, improving the immune system. This experimental survey aimed to assess the efficacy of QBA against tachyzoites and intracellular parasites of the RH strain. Anti- effects of QBA against tachyzoites were examined by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay for 30, 60, 120, and 180 min. In addition, the effect of QBA on infection rate and intracellular parasites was studied. Real-time polymerase chain reaction (Real-Time PCR) was also applied to assess the expression level of the Caspase-3 gene. The best efficiency of QBA was obtained at 100 and 50 µg/mL, whereas all tachyzoites were diminished, followed by 120- and 180-min treatment, respectively. It was also found that the best repressing efficacy of QBA in the infection rate and the load of parasites into the Vero cells was indicated at 100 µg/mL (<0.001). Nonetheless, the combination of QBA (12.5 µg/mL) along with atovaquone 30 µg/mL displayed the most marked effect on the infection rate and a load of parasites into the Vero cells in the infected Vero cells. The expression level of the Caspase-3 gene was dose-dependently increased after the exposure of tachyzoites to QBA, mainly at ½ IC and IC compared to normal saline. The obtained findings exhibited the high potency of QBA, especially in combination with atovaquone against RH strain tachyzoites. Although apoptosis induction can be suggested as one of the principle mechanisms, more studies are required to elucidate its accurate mechanisms, as well as its efficacy and safety in animal models and clinical settings.

摘要

弓形虫病是一种寄生虫引起的传染病。10-羟基-2-癸烯酸(10-H2DA,蜂王酸(QBA))是蜂王浆中最常见的脂肪酸之一(>40%)。研究表明,10-H2DA 具有抗肿瘤、抗炎、抗血管生成和抗菌作用,可改善免疫系统。本实验旨在评估 QBA 对 RH 株速殖子和细胞内寄生虫的疗效。通过 MTT(3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴盐)法在 30、60、120 和 180 分钟检测 QBA 对速殖子的抗作用。此外,还研究了 QBA 对感染率和细胞内寄生虫的影响。还应用实时聚合酶链反应(Real-Time PCR)评估 Caspase-3 基因的表达水平。在 100 和 50 µg/mL 时,QBA 的效率最佳,所有速殖子均被消除,随后分别进行 120 和 180 分钟的处理。还发现,QBA 在感染率和寄生虫负荷方面的最佳抑制效果表明在 100 µg/mL(<0.001)。然而,QBA(12.5 µg/mL)与阿托伐醌 30 µg/mL 联合使用对感染的 Vero 细胞中的感染率和寄生虫负荷显示出最显著的效果。速殖子暴露于 QBA 后,Caspase-3 基因的表达水平呈剂量依赖性增加,与生理盐水相比,主要在半 IC 和 IC 时增加。研究结果表明,QBA 具有很高的效力,尤其是与阿托伐醌联合使用时,对 RH 株速殖子具有很高的效力。虽然可以推测凋亡诱导是其主要机制之一,但需要进一步研究以阐明其确切机制,以及在动物模型和临床环境中的疗效和安全性。

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