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)

References

[1]	PAN J, ZHANG M, YAO TT, et al. Efficiency and influencing factors of interferon therapy for 1-6 years old children with chronic hepatitis B[J]. Int J Virol, 2020, 27(3): 214-218. DOI: 10.3760/cma.j.issn.1673-4092.2020.03.009. 潘静, 张敏, 姚甜甜, 等. 干扰素治疗1~6岁慢性乙型肝炎的疗效及影响因素[J]. 国际病毒学杂志, 2020, 27(3): 214-218. DOI: 10.3760/cma.j.issn.1673-4092.2020.03.009.
[2]	REVILL PA, PENICAUD C, BRECHOT C, et al. Meeting the challenge of eliminating chronic hepatitis B infection[J]. Genes (Basel), 2019, 10(4): 260. DOI: 10.3390/genes10040260.
[3]	ZHENG X, LIU J, WU J, et al. Advances and challenges in immune control and functional cure of chronic hepatitis B[J]. J Clin Hepatol, 2020, 36(5): 961-964. DOI: 10.3969/j.issn.1001-5256.2020.05.001 郑昕, 刘嘉, 吴珺, 等. 免疫控制与慢性乙型肝炎功能性治愈的进展与挑战[J]. 临床肝胆病杂志, 2020, 36(5): 961-964. DOI: 10.3969/j.issn.1001-5256.2020.05.001.
[4]	van de LAAR TJ, van GAEVER VA, SWIETEN PV, et al. Phylogenetic analysis reveals three distinct epidemiological profiles in Dutch and Flemish blood donors with hepatitis B virus infection[J]. Virology, 2018, 515: 243-249. DOI: 10.1016/j.virol.2017.12.011.
[5]	ZHOU R, CHEN H, CHEN J, et al. Extract from Astragalus membranaceus inhibit breast cancer cells proliferation via PI3K/AKT/mTOR signaling pathway[J]. BMC Complement Altern Med, 2018, 18(1): 83. DOI: 10.1186/s12906-018-2148-2.
[6]	CHE D, ADAMS S, WEI C, et al. Effects of Astragalus membranaceus fiber on growth performance, nutrient digestibility, microbial composition, VFA production, gut pH, and immunity of weaned pigs[J]. Microbiologyopen, 2019, 8(5): e00712. DOI: 10.1002/mbo3.712.
[7]	LUO Y, WAN Q, XU M, et al. Nutritional preconditioning induced by astragaloside Ⅳ on isolated hearts and cardiomyocytes against myocardial ischemia injury via improving Bcl-2-mediated mitochondrial function[J]. Chem Biol Interact, 2019, 309: 108723. DOI: 10.1016/j.cbi.2019.06.036.
[8]	LU M, TANG F, ZHANG J, et al. Astragaloside Ⅳ attenuates injury caused by myocardial ischemia/reperfusion in rats via regulation of toll-like receptor 4/nuclear factor-κ B signaling pathway[J]. Phytother Res, 2015, 29(4): 599-606. DOI: 10.1002/ptr.5297.
[9]	WU S, LI XF, WANG QT, et al. Effects of fermented milkvetch root on proliferation and expression of aging-related proteins in human embryonic lung diploid fibroblast cell[J]. J Changchun Univ Chin Med, 2020, 36(4): 676-679. DOI: 10.13463/j.cnki.cczyy.2020.04.019. 吴爽, 李学锋, 王秋彤, 等. 发酵黄芪对人胚肺二倍体成纤维细胞增殖及衰老相关蛋白表达的影响[J]. 长春中医药大学学报, 2020, 36(4): 676-679. DOI: 10.13463/j.cnki.cczyy.2020.04.019.
[10]	CHEN CC, CHANG LC, YAO CH, et al. Increased calcitonin gene-related peptide and macrophages are involved in astragalus membranaceus-mediated peripheral nerve regeneration in rats[J]. Am J Chin Med, 2018, 46(1): 69-86. DOI: 10.1142/S0192415X18500040.
[11]	WU XM, YUAN WS. In vitro study of the anti - HBV activity of astragalus[J]. Guangdong Med J, 2008, 29(1): 37-38. DOI: 10.13820/j.cnki.gdyx.2008.01.003. 吴晓蔓, 袁文声. 黄芪抗乙型肝炎病毒的体外实验研究[J]. 广东医学, 2008, 29(1): 37-38. DOI: 10.13820/j.cnki.gdyx.2008.01.003.
[12]	YAN JY. Effect and mechanism of huangqi injection combined with entecavir against hepatitis B virus infection[D]. Guangzhou: Guangzhou University of Chinese Medicine, 2015. 严景妍. 黄芪注射液联合恩替卡韦抗乙型肝炎病毒感染机理研究[D]. 广州: 广州中医药大学, 2015.
[13]	ZHANG J, CHEN JZ, ZHANG JP, et al. Inhibitory effect of astragaloside Ⅳ on human hepatitis B virus replication in vitro[J]. J Fourth MilMed Univ, 2007, 28(24): 2291-2293. DOI: 1000-2790(2007)24-2291-03. 张娟, 陈建宗, 张金平, 等. 黄芪甲甙体外抗乙型肝炎病毒的作用[J]. 第四军医大学学报, 2007, 28(24): 2291-2293. DOI: 1000-2790(2007)24-2291-03.
[14]	XU D, WANG Y, WU J, et al. MTIF2 impairs 5 fluorouracil-mediated immunogenic cell death in hepatocellular carcinoma in vivo: Molecular mechanisms and therapeutic significance[J]. Pharmacol Res, 2021, 163: 105265. DOI: 10.1016/j.phrs.2020.105265.
[15]	OVERMAN RG JR, ENDERLE PJ, FARROW JM 3rd, et al. The human mitochondrial translation initiation factor 2 gene (MTIF2): transcriptional analysis and identification of a pseudogene[J]. Biochim Biophys Acta, 2003, 1628(3): 195-205. DOI: 10.1016/s0167-4781(03)00144-1.
[16]	LEE DE, PERRY RA JR, BROWN JL, et al. Mitochondrial mRNA translation initiation contributes to oxidative metabolism in the myocardia of aged, obese mice[J]. Exp Gerontol, 2019, 121: 62-70. DOI: 10.1016/j.exger.2019.03.009.
[17]	ZHONG Y, LIU DL, AHMED M, et al. Transcription and regulation of hepatitis B virus genes in host sperm cells[J]. Asian J Androl, 2018, 20(3): 284-289. DOI: 10.4103/aja.aja_46_17.
[18]	HEDGES J, WEST M, JOHNSON AW. Release of the export adapter, Nmd3p, from the 60S ribosomal subunit requires Rpl10p and the cytoplasmic GTPase Lsg1p[J]. EMBO J, 2005, 24(3): 567-579. DOI: 10.1038/sj.emboj.7600547.
[19]	YE YS, CHANG K, ZHU ZY, et al. Gemcitabine promotes hepatitis B virus pgRNA transcription and viral replication in HepG2.2.15 cells and related molecular mechanisms[J]. J Chongqing Med Univ, 2019, 44(12): 1564-1570. DOI: 10.13406/j.cnki.cyxb.002221. 叶雨笙, 常凯, 朱紫衣, 等. 吉西他滨促进HepG2.2.15细胞系中乙肝病毒pgRNA转录和病毒复制及相关分子机制研究[J]. 重庆医科大学学报, 2019, 44(12): 1564-1570. DOI: 10.13406/j.cnki.cyxb.002221.
[20]	GU XL. MicroRNA-124 prevents H₂O₂-induced apoptosis and oxidative stress in human lens epithelial cells via inhibition of the NF-κ B signaling pathway[J]. Pharmacology, 2018, 102(3-4): 213-222. DOI: 10.1159/000491433.
[21]	VLASBLOM J, ZUBERI K, RODRIGUEZ H, et al. Novel function discovery with GeneMANIA: a new integrated resource for gene function prediction in Escherichia coli[J]. Bioinformatics, 2015, 31(3): 306-310. DOI: 10.1093/bioinformatics/btu671.
[22]	MOHD-ISMAIL NK, LIM Z, GUNARATNE J, et al. Mapping the interactions of HBV cccDNA with host factors[J]. Int J Mol Sci, 2019, 20(17): 4276. DOI: 10.3390/ijms20174276.
[23]	FRITZLAR S, AKTEPE TE, CHAO YW, et al. Mouse norovirus infection arrests host cell translation uncoupled from the stress granule-PKR-eIF2αaxis[J]. mBio, 2019, 10(3): e00960-19. DOI: 10.1128/mBio.00960-19.
[24]	TEO C, O'HARE P. A bimodal switch in global protein translation coupled to eIF4H relocalisation during advancing cell-cell transmission of herpes simplex virus[J]. PLoS Pathog, 2018, 14(7): e1007196. DOI: 10.1371/journal.ppat.1007196.
[25]	HU YM, LIU LH, LIU BC, et al. Radioprotective effects of astragaloside Ⅳ on the liver cell[J]. J Radiat Res Radiat Process, 2015, 33(6): 19-24. DOI: 10.11889/j.1000-3436.2015.rrj.33.060202. 胡雅梦, 刘琅嬛, 刘宝婵, 等. 黄芪甲苷对肝细胞的辐射防护作用[J]. 辐射研究与辐射工艺学报, 2015, 33(6): 19-24. DOI: 10.11889/j.1000-3436.2015.rrj.33.060202.
[26]	LIU L, LI SJ, ZHOU Y. Protective effect of astragaloside Ⅳ against acute liver failure in experimental mice[J]. Chin J Hepatol, 2016, 24(10): 772-777. DOI: 10.3760/cma.j.issn.1007-3418.2016.10.011. 刘丽, 李双杰, 周宇. 黄芪甲苷对实验性急性肝衰竭小鼠的保护作用[J]. 中华肝脏病杂志, 2016, 24(10): 772-777. DOI: 10.3760/cma.j.issn.1007-3418.2016.10.011.
[27]	RINGELHAN M, MCKEATING JA, PROTZER U. Viral hepatitis and liver cancer[J]. Philos Trans R Soc Lond B Biol Sci, 2017, 372(1732): 20160274. DOI: 10.1098/rstb.2016.0274.
[28]	LUBYOVÁ B, WEBER J. Posttranslational modifications of HBV core protein[J]. Acta Virol, 2020, 64(2): 177-186. DOI: 10.4149/av_2020_207.

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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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