研究动态
Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

香豆素戊醚在小鼠全身念珠菌症模型中的生长抑制和凋亡效应。

The growth inhibitory and apoptotic effects of umbelliprenin in a mouse model of systemic candidiasis.

发表日期:2023 Sep 05
作者: Mohsen Rashidi, Ali Bazi, Alireza Ahmadzadeh, Orazio Romeo, Ali Rezaei-Matehkolaei, Mahdi Abastabar, Iman Haghani, Sepideh Mirzaei
来源: TROPICAL MEDICINE & INTERNATIONAL HEALTH

摘要:

紫芹内酯表现出了很有前途的生物活性,包括免疫调节、抗炎和抗癌作用。本研究探讨了紫芹内酯对BALB/c小鼠播散性念珠菌感染模型中念珠菌生长抑制和诱导细胞凋亡的影响。首先,进行了微量稀释敏感性测试以进行抗菌测定。然后,将25只6周龄的雌性BALB/c小鼠(20±12g)分为五组,包括一个对照组(无紫芹内酯治疗)和四个实验组:念珠菌感染的小鼠分别接受紫芹内酯剂量为5、10、20和40mg kg-1的处理。检查大脑、肺、肾脏、脾脏和肝脏组织,观察真菌感染和组织病理学损伤情况,并进行TUNEL染色以评估细胞凋亡。使用β-1, 3-葡聚糖合酶活性测定来评估酶活性,并进行基因表达分析以研究ERG11、CDR1、ALS1和HWP1基因的转录变化。紫芹内酯的最小抑菌浓度(MIC)为1.5 mg mL-1。我们的研究结果显示,在40 mg kg-1剂量下,紫芹内酯能够消除BALB/c小鼠中的真菌感染。紫芹内酯处理组中的凋亡细胞百分比呈浓度依赖性增加。紫芹内酯(40 mg kg-1)还抑制了β-1, 3-葡聚糖合酶的表达,以及与抗真菌耐药性相关的基因(CDR1和ERG11)的表达,以及与粘附蛋白(ALS1和HWP1)编码基因的表达。我们的研究结果显示,紫芹内酯能够通过诱导凋亡部分地促进抗真菌效应。© 作者(2023)。由牛津大学出版社代表应用微生物国际出版。
Umbelliprenin has shown promising biological activities, including immunoregulatory, anti-inflammatory, and anti-cancer effects. The present study investigated the growth inhibitory and apoptotic effects of umbelliprenin against Candida albicans in a BALB/c mice model of disseminated candidiasis.First, an antimicrobial assay via micro-dilution sensitivity test was performed. Then twenty-five 6-week-old female BALB/c mice (20 ± 12 g) were divided into five groups of five mice, including one control group (no umbelliprenin treatment) and four experimental groups: C. albicans-infected mice treated with umbelliprenin at the doses of 5, 10, 20, and 40 mg kg -1. The brain, lung, kidney, spleen, and liver tissues were examined for fungal infection and histological lesions, and TUNEL staining was performed to assess apoptosis. The β-1, 3-glucan synthase assay was used to evaluate enzymatic activity, and gene expression analysis was also performed to investigate the transcriptional changes of ERG11, CDR1, ALS1, and HWP1 genes. The MIC of umbelliprenin was 1.5 mg mL-1. Our results showed that at the 40 mg kg -1 dose, umbelliprenin was able to eradicate fungal infection in BALB/c mice. The percentage of apoptotic cells in umbelliprenin-treated groups increased in a concentration-dependent manner. Umbelliprenin (40 mg kg -1) also inhibited the expression of β-1, 3-glucan synthase, and the genes involved in antifungal resistance (CDR1 and ERG11), as well as the expression of the genes encoding adhesins (ALS1 and HWP1).Our results showed that umbelliprenin could promote antifungal effects, partly via inducing apoptosis.© The Author(s) 2023. Published by Oxford University Press on behalf of Applied Microbiology International.