Abstract

Context

18β-Glycyrrhetinic acid (18β-GA), a pentacyclic triterpenoid saponin metabolite of glycyrrhizin, exhibits several biological activities.

Objective

We investigated the effects of 18β-GA on MA104 cells infected with rotavirus (RV) and its potential mechanism of action.

Materials and methods

Cell Counting Kit-8 was used to assess tissue culture infective dose 50 (TCID₅₀) and 50% cellular cytotoxicity (CC₅₀) concentration. MA104 cells infected with RV SA11 were treated with 18β-GA (1, 2, 4, and 8 μg/mL, respectively). Cytopathic effects were observed. The virus inhibition rate, concentration for 50% of maximal effect (EC₅₀), and selection index (SI) were calculated. Cell cycle, cell apoptosis, and mRNA and protein expression related to the Fas/FasL pathway were detected.

Results

TCID₅₀ of RV SA11 was 10^−4.47/100 µL; the CC₅₀ of 18β-GA on MA104 cells was 86.92 µg/mL. 18β-GA showed significant antiviral activity; EC₅₀ was 3.14 μg/mL, and SI was 27.68. The ratio of MA104 cells infected with RV SA11 in the G0/G1 phase and the G2/M phase decreased and increased, respectively, after 18β-GA treatment. 18β-GA significantly induced apoptosis in the infected cells. Furthermore, after 18β-GA treatment, the mRNA and protein expression levels of Fas, FasL, caspase 3, and Bcl-2 decreased, whereas the expression levels of Bax increased.

Discussion and conclusions

The study demonstrates that 18β-GA may be a promising candidate for the treatment of RV SA11 infection and provides theoretical support for the clinical development of glycyrrhizic acid compounds for the treatment of RV infection.

中文翻译：

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18β-甘草次酸通过Fas/FasL通路抑制轮状病毒SA11感染细胞的凋亡

摘要

语境

18β-Glycyrrhetinic acid (18β-GA) 是一种甘草甜素的五环三萜皂苷代谢物，具有多种生物活性。

客观的

我们研究了 18β-GA 对感染轮状病毒 (RV) 的 MA104 细胞的影响及其潜在的作用机制。

材料和方法

Cell Counting Kit-8 用于评估组织培养感染剂量 50 (TCID ₅₀ ) 和 50% 细胞毒性 (CC ₅₀ ) 浓度。用 18β-GA（分别为 1、2、4 和 8 μg/mL）处理感染了 RV SA11 的 MA104 细胞。观察到细胞病变效应。计算病毒抑制率、50%最大效应浓度（EC ₅₀）和选择指数（SI）。检测细胞周期、细胞凋亡以及与Fas/FasL通路相关的mRNA和蛋白表达。

结果

RV SA11 的TCID ₅₀为 10 ^-4.47 /100 µL；MA104 细胞上 18β-GA的 CC ₅₀为 86.92 µg/mL。18β-GA显示出显着的抗病毒活性；EC ₅₀为 3.14 μg/mL，SI 为 27.68。18β-GA处理后，在G0/G1期和G2/M期感染RV SA11的MA104细胞比例分别降低和升高。18β-GA显着诱导感染细胞的凋亡。此外，18β-GA 处理后，Fas、FasL、caspase 3 和 Bcl-2 的 mRNA 和蛋白表达水平降低，而 Bax 的表达水平升高。

讨论和结论

该研究表明，18β-GA可能是治疗RV SA11感染的有希望的候选者，并为临床开发用于治疗RV感染的甘草酸化合物提供理论支持。