Departmentof Biological Sciences, Faculty of Science and Humanities, Shaqra University, Ad-Dawadimi, Saudi Arabia.
Department of Basic Science, Faculty of Medicine, Almaarefa University, Riyadh, Saudi Arabia.
Front Cell Infect Microbiol. 2022 Jun 9;12:900046. doi: 10.3389/fcimb.2022.900046. eCollection 2022.
This experimental study determined the , , and toxicity effects of methanolic extract (CZME) against infection.
The activity of CZME tachyzoites was studied by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Infected mice were treated with CZME for two weeks at doses of 20, 40, and 60 mg/kg/day. Then, the therapeutic effects of CZME were evaluated by assessing the mean number and mean size of tissue cysts, oxidant-antioxidant enzymes, pro-inflammatory cytokines, and mRNA expression levels of bradyzoite surface antigen 1 (BAG1) by real-time PCR.
CZME significantly (p <0.001) increased the mortality rate of parasites in a dose- and time-dependent response. The mean number of intracellular tachyzoites was significantly reduced after CZME therapy. The treatment of infected mice with CZME resulted in a significant (p <0.001) downregulation of BAG1 and the level of lipid peroxidation (LPO) and nitric oxide (NO) as oxidative stress markers. However, a considerable rise (p <0.05) was found in the levels of antioxidant markers such as glutathione peroxidase (GPx), catalase enzyme (CAT), and superoxide dismutase enzyme activity (SOD). In a dose-dependent response, after treatment of infected mice with CZME, the level of pro-inflammatory cytokines of IFN-γ, IL-1β, and IL-12 was considerably elevated. CZME had no significant cytotoxicity on Vero cells, with a 50% cytotoxic concentration of 169.5 ± 5.66 μg/ml.
The findings confirmed the promising therapeutic effects of CZME on chronic toxoplasmosis in mice. Nevertheless, further investigations must confirm these results, elucidate its precise mechanisms, and examine its effectiveness in human volunteers.
本实验研究了甲醇提取物（CZME）对感染的、、毒性作用。
通过 MTT（3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐）测定法研究 CZME 对速殖子的活性。用 CZME 以 20、40 和 60 mg/kg/天的剂量治疗感染的小鼠两周。然后，通过评估组织包囊的平均数量和平均大小、氧化应激酶、促炎细胞因子以及实时 PCR 检测缓殖子表面抗原 1（BAG1）的 mRNA 表达水平来评估 CZME 的治疗效果。
CZME 以剂量和时间依赖的方式显著（p <0.001）增加寄生虫的死亡率。用 CZME 治疗后，细胞内速殖子的数量明显减少。用 CZME 治疗感染的小鼠导致 BAG1 和脂质过氧化（LPO）和一氧化氮（NO）水平显著下调（p <0.001）作为氧化应激标志物。然而，抗氧化标志物如谷胱甘肽过氧化物酶（GPx）、过氧化氢酶酶（CAT）和超氧化物歧化酶酶活性（SOD）的水平发现明显升高（p <0.05）。在剂量依赖性反应中，用 CZME 治疗感染的小鼠后，IFN-γ、IL-1β 和 IL-12 的促炎细胞因子水平明显升高。CZME 对 Vero 细胞没有明显的细胞毒性，半数细胞毒性浓度为 169.5 ± 5.66 μg/ml。
这些发现证实了 CZME 对小鼠慢性弓形虫病有很好的治疗效果。然而，必须进行进一步的研究来证实这些结果，阐明其确切的机制，并研究其在人类志愿者中的有效性。
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