Mechanism of astragaloside Ⅳ inhibits hepatitis B virus replication by regulating host ribosome translation process

Kai CHANG; Yanyan WANG; Wanlin NA; Chenxia LIU; Yusheng YE; Zhongyong JIANG; Yuan LIU

doi:10.3969/j.issn.1001-5256.2022.07.009

Volume 38 Issue 7

Jul. 2022

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Article Navigation > Journal of Clinical Hepatology > 2022 > 38(7): 1495-1502

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Mechanism of astragaloside Ⅳ inhibits hepatitis B virus replication by regulating host ribosome translation process

DOI: 10.3969/j.issn.1001-5256.2022.07.009

1.
Department of Clinical Laboratory, The General Hospital of Western Theater Command, Chengdu 610083, China
2.
Institute of Microbiology, Sichuan Provincial Center for Disease Control and Prevention, Chengdu 610041, China
3.
Department of Clinical Laboratory, People's Hospital of Pidu District & The Third Affiliated Hospital of Chengdu Medical College, Chengdu 611730, China
4.
Department of Clinical Laboratory, Affiliated Cancer Hospital of Chengdu Medical College & Chengdu Seventh People's Hospital, Chengdu 610041, China

Research funding:

The Special Project of Sichuan Province Traditional Chinese Medicine Administration (2020JC0124);

The General Hospital of Western Theater Command Management Project of Science and The Spark Young Innovative Talent Project ;

The Applied Basic Research Program of The General Hospital of Western Theater Command (2021-XZYG-C22);

National Natural Science Foundation of China (81301445)

More Information

Corresponding author: LIU Yuan, liuyuan198231@163.com (ORCID: 0000-0002-4387-2250)
Received Date: 2021-11-11
Accepted Date: 2022-01-20
Published Date: 2022-07-20

Abstract

Abstract

Objective To investigate the host regulatory mechanism of astragaloside Ⅳ in inhibiting hepatitis B virus (HBV) replication. Methods Normal human hepatocytes L-02 were treated with different concentrations of astragaloside Ⅳ, and according to the concentration of astragaloside Ⅳ, the cells were divided into 0, 5, 10, and 20 μg/mL groups. CCK-8 assay was used to measure cell viability, flow cytometry was used to measure cell apoptosis, and chemiluminescence and biochemical methods were used to measure the levels of alpha-fetoprotein (AFP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), so as to evaluate the influence of astragaloside Ⅳ on normal cells. Hepatoma cells Hep3B carrying HBV were treated with astragaloside Ⅳ; quantitative PCR was used to measure the mRNA expression levels of HBV DNA, pgRNA, MTIF2, and RPL10, and ELISA was used to measure the levels of HBsAg and HBeAg, so as to evaluate the effect of astragaloside Ⅳ on HBV replication. TCGA and GEO databases combined with R language package were used to analyze the prognostic effect of RPL10 and MTIF2 in clinical samples. The Kaplan-Meier method was used for survival analysis, and the log-rank test was used for comparison of survival between two or multiple groups; the time-dependent ROC curve analysis was performed to compare the predictive accuracy and risk score of RPL10 and MTIF2 genes. A one-way analysis of variance was used for comparison of continuous data between multiple groups and within each group at different time points, and the Bonferroni method was used for further comparison between two groups. Results Compared with the untreated group, the 20 μg/mL group had a significant increase in cell growth activity at 24 and 48 hours of treatment (both P < 0.05); compared with the 10 μg/mL group, the 20 μg/mL group had a significant increase in cell growth activity at 72 hours of treatment (P < 0.05); compared with the untreated group, the 5 μg/mL group had a significant increase in cell growth activity at 72 hours of treatment (P < 0.05). Compared with the untreated group, the 5, 10, and 20 μg/mL groups had a significant increase in AFP (all P < 0.05); compared with the untreated group and the 5 μg/mL group, the 10 and 20 μg/mL groups had a significant reduction in ALT (all P < 0.05), and compared with the 10 μg/mL group, the 20 μg/mL group had a significant reduction in ALT (P < 0.05). Compared with the untreated group, the 5, 10, and 20 μg/mL groups had a significant increase in AST (all P < 0.05). There were significant differences in the levels of HBV DNA, pgRNA, HBsAg, HBeAg, RPL10, and MTIF2 between the 5/10/20 μg/mL groups and the untreated group (all P < 0.05). The bioinformatics analysis showed that among the liver cancer patients with HBV infection, the patients with high mRNA expression levels of RPL10 and MTIF2 genes tended to have a poor prognosis, while this phenomenon was not observed in liver cancer patients without HBV infection. Conclusion Astragaloside Ⅳ can inhibit the translation initiation factor MTIF2 and the large ribosomal subunit RPL10 and reduce HBV replication by regulating the initiation of host ribosome translation.
- Astragaloside Ⅳ,
- Hepatitis B virus,
- Ribosomal Proteins

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References(28)

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Mechanism of astragaloside Ⅳ inhibits hepatitis B virus replication by regulating host ribosome translation process

DOI: 10.3969/j.issn.1001-5256.2022.07.009

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Mechanism of astragaloside Ⅳ inhibits hepatitis B virus replication by regulating host ribosome translation process

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