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IMMUNOLOGY / RESEARCH PAPER
Oxymatrine blocked mother-to-child transmission of hepatitis B virus by modulating autophagy in trophoblast cells
1
Zhejiang Provincial People’s Hospital, China
2
Zhejiang Chinese Medical University, China
These authors had equal contribution to this work
Submission date: 2025-01-24
Final revision date: 2025-05-24
Acceptance date: 2025-07-12
Online publication date: 2025-08-23
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Mother-to-child transmission is a significant pathway for chronic carriers of the hepatitis B virus (HBV) in China. In this study, we aimed to investigate the role and mechanism of Oxymatrine (OMT) in preventing mother-to-child transmission of HBV.
Material and methods:
To simulate MTCT, we utilized the HBV-infected human trophoblast cell line HTR-8/SVneo, which serves as a relevant model for studying HBV transmission at the maternal-fetal interface. The replication capacity of HBV in these cells was quantified using enzyme-linked immunosorbent assay (ELISA) and real-time fluorescence polymerase chain reaction (PCR). The expression levels of key autophagy markers were assessed using Western blotting, providing insights into the autophagy-related mechanisms potentially involved. Additionally, the Cell Counting Kit-8 (CCK-8) assay was employed to measure the proliferation of trophoblast cells under different treatment conditions.
Results:
We found that OMT inhibited HBV DNA replication in HBV-infected trophoblast cells. Additionally, OMT suppressed the proliferation and autophagy in HBV-infected trophoblast cells. This suggested that OMT might effectively block mother-to-child transmission of HBV. Mechanistically, OMT appears to prevent mother-to-child transmission of HBV by inhibiting the EGFR/Akt pathway.
Conclusions:
OMT inhibited HBV transmission by regulating the EGFR/Akt pathway, and this study may provide new ideas and methods for the prevention of mother-to-child transmission of HBV infection during pregnancy.
Mother-to-child transmission is a significant pathway for chronic carriers of the hepatitis B virus (HBV) in China. In this study, we aimed to investigate the role and mechanism of Oxymatrine (OMT) in preventing mother-to-child transmission of HBV.
Material and methods:
To simulate MTCT, we utilized the HBV-infected human trophoblast cell line HTR-8/SVneo, which serves as a relevant model for studying HBV transmission at the maternal-fetal interface. The replication capacity of HBV in these cells was quantified using enzyme-linked immunosorbent assay (ELISA) and real-time fluorescence polymerase chain reaction (PCR). The expression levels of key autophagy markers were assessed using Western blotting, providing insights into the autophagy-related mechanisms potentially involved. Additionally, the Cell Counting Kit-8 (CCK-8) assay was employed to measure the proliferation of trophoblast cells under different treatment conditions.
Results:
We found that OMT inhibited HBV DNA replication in HBV-infected trophoblast cells. Additionally, OMT suppressed the proliferation and autophagy in HBV-infected trophoblast cells. This suggested that OMT might effectively block mother-to-child transmission of HBV. Mechanistically, OMT appears to prevent mother-to-child transmission of HBV by inhibiting the EGFR/Akt pathway.
Conclusions:
OMT inhibited HBV transmission by regulating the EGFR/Akt pathway, and this study may provide new ideas and methods for the prevention of mother-to-child transmission of HBV infection during pregnancy.
REFERENCES (42)
2.
Chen, Y. and Z. Tian, HBV-Induced Immune Imbalance in the Development of HCC. Front Immunol, 2019. 10: p. 2048.
3.
Jing, W., J. Liu, and M. Liu, Eliminating mother-to-child transmission of HBV: progress and challenges in China. Front Med, 2020. 14(1): p. 21-29.
4.
Chen, Y., et al., Role of maternal viremia and placental infection in hepatitis B virus intrauterine transmission. Microbes Infect, 2013. 15(5): p. 409-15.
5.
Delorme-Axford, E., et al., Human placental trophoblasts confer viral resistance to recipient cells. Proc Natl Acad Sci U S A, 2013. 110(29): p. 12048-53.
6.
Liu, S., et al., Autophagy: Regulator of cell death. Cell Death Dis, 2023. 14(10): p. 648.
7.
Chiramel, A.I. and S.M. Best, Role of autophagy in Zika virus infection and pathogenesis. Virus Res, 2018. 254: p. 34-40.
8.
Miller, K., et al., Coronavirus interactions with the cellular autophagy machinery. Autophagy, 2020. 16(12): p. 2131-2139.
9.
Chan, S.T. and J.J. Ou, Hepatitis C Virus-Induced Autophagy and Host Innate Immune Response. Viruses, 2017. 9(8).
10.
Gao, H., et al., The Role of Autophagy in the Mother-to-Child Transmission of Pregnant Women With a High Level of HBV DNA. Front Cell Infect Microbiol, 2022. 12: p. 850747.
11.
Cui, H., et al., Hepatitis B virus X protein modifies invasion, proliferation and the inflammatory response in an HTR-8/SVneo cell model. Oncol Rep, 2015. 34(4): p. 2090-8.
12.
Dai, Y.J., et al., Recent advances of traditional Chinese medicine on the prevention and treatment of COVID-19. Chin J Nat Med, 2020. 18(12): p. 881-889.
13.
Li, T. and T. Peng, Traditional Chinese herbal medicine as a source of molecules with antiviral activity. Antiviral Res, 2013. 97(1): p. 1-9.
14.
Ren, W., et al., Research progress of traditional Chinese medicine against COVID-19. Biomed Pharmacother, 2021. 137: p. 111310.
15.
Lan, X., et al., Oxymatrine exerts organ- and tissue-protective effects by regulating inflammation, oxidative stress, apoptosis, and fibrosis: From bench to bedside. Pharmacol Res, 2020. 151: p. 104541.
16.
Sang, X., et al., T cell--associated immunoregulation and antiviral effect of oxymatrine in hydrodynamic injection HBV mouse model. Acta Pharm Sin B, 2017. 7(3): p. 311-318.
17.
Xu, W.S., et al., Effect of oxymatrine on the replication cycle of hepatitis B virus in vitro. World J Gastroenterol, 2010. 16(16): p. 2028-37.
18.
Song, W.J., et al., Oral oxymatrine preparation for chronic hepatitis B: A systematic review of randomized controlled trials. Chin J Integr Med, 2016. 22(2): p. 141-9.
19.
Cui, H., J. Chen, and Q. Na, Effect of hepatitis B virus infection on trophoblast cell line (HTR-8/SVneo) and choriocarcinoma cell line (JEG3) is linked to CD133-2 (AC141) expression. Am J Transl Res, 2016. 8(7): p. 3235-40.
20.
Cheung, K.W., M.T.Y. Seto, and T.T. Lao, Prevention of perinatal hepatitis B virus transmission. Arch Gynecol Obstet, 2019. 300(2): p. 251-259.
21.
Ma, L., et al., Mother-to-child transmission of HBV: review of current clinical management and prevention strategies. Rev Med Virol, 2014. 24(6): p. 396-406.
22.
Mavilia, M.G. and G.Y. Wu, Mechanisms and Prevention of Vertical Transmission in Chronic Viral Hepatitis. J Clin Transl Hepatol, 2017. 5(2): p. 119-129.
23.
Bai, G., et al., The study on the role of hepatitis B virus X protein and apoptosis in HBV intrauterine infection. Arch Gynecol Obstet, 2012. 285(4): p. 943-9.
24.
Abbas, Y., et al., Investigation of human trophoblast invasion in vitro. Hum Reprod Update, 2020. 26(4): p. 501-513.
25.
Lai, T.H., H.T. Chen, and W.B. Wu, Trophoblast coculture induces intercellular adhesion molecule-1 expression in uterine endometrial epithelial cells through TNF-α production: Implication of role of FSH and ICAM-1 during embryo implantation. J Reprod Immunol, 2022. 152: p. 103650.
26.
Jackson, W.T., Autophagy as a broad antiviral at the placental interface. Autophagy, 2013. 9(12): p. 1905-7.
27.
Liu, D.X., et al., Exosomes derived from HBV-associated liver cancer promote chemoresistance by upregulating chaperone-mediated autophagy. Oncol Lett, 2019. 17(1): p. 323-331.
28.
He, Q., et al., Dexamethasone Stimulates Hepatitis B Virus (HBV) Replication Through Autophagy. Med Sci Monit, 2018. 24: p. 4617-4624.
29.
Wu, S.Y., S.H. Lan, and H.S. Liu, Autophagy and microRNA in hepatitis B virus-related hepatocellular carcinoma. World J Gastroenterol, 2016. 22(1): p. 176-87.
30.
Wang, D.D., et al., Relationship between Maternal PBMC HBV cccDNA and HBV Serological Markers and its Effect on HBV Intrauterine Transmission. Biomed Environ Sci, 2019. 32(5): p. 315-323.
31.
Huan, D.Q., N.Q. Hop, and N.T. Son, Oxymatrine: A current overview of its health benefits. Fitoterapia, 2023. 168: p. 105565.
32.
Lin, M., et al., Inhibition of the replication of hepatitis B virus in vitro by oxymatrine. J Int Med Res, 2009. 37(5): p. 1411-9.
33.
Lu, L.G., et al., Inhibitory effect of oxymatrine on serum hepatitis B virus DNA in HBV transgenic mice. World J Gastroenterol, 2004. 10(8): p. 1176-9.
34.
Jiang, X., et al., Oral oxymatrine for hepatitis B cirrhosis: A systematic review protocol. Medicine (Baltimore), 2018. 97(49): p. e13482.
35.
Lu, L.G., et al., Oxymatrine therapy for chronic hepatitis B: a randomized double-blind and placebo-controlled multi-center trial. World J Gastroenterol, 2003. 9(11): p. 2480-3.
36.
Cui, X., et al., Blockage of EGFR/AKT and mevalonate pathways synergize the antitumor effect of temozolomide by reprogramming energy metabolism in glioblastoma. Cancer Commun (Lond), 2023. 43(12): p. 1326-1353.
37.
Jing, X., et al., IGF2BP3-EGFR-AKT axis promotes breast cancer MDA-MB-231 cell growth. Biochim Biophys Acta Mol Cell Res, 2023. 1870(8): p. 119542.
38.
Wang, W., et al., HBxAg suppresses cell apoptosis and promotes the secretion of placental hormones in human placental trophoblasts via activation of the EGFR/Akt pathway. Cell Biol Int, 2018. 42(2): p. 237-247.
39.
Lin, Y., et al., HBxAg promotes HBV replication and EGFR activation in human placental trophoblasts. Exp Ther Med, 2021. 22(5): p. 1211.
40.
Guo, B., et al., Oxymatrine targets EGFR(p-Tyr845) and inhibits EGFR-related signaling pathways to suppress the proliferation and invasion of gastric cancer cells. Cancer Chemother Pharmacol, 2015. 75(2): p. 353-63.
41.
Halim, C.E., et al., Anti-cancer effects of oxymatrine are mediated through multiple molecular mechanism(s) in tumor models. Pharmacol Res, 2019. 147: p. 104327.
42.
Dai, Z., et al., Oxymatrine induces cell cycle arrest and apoptosis and suppresses the invasion of human glioblastoma cells through the EGFR/PI3K/Akt/mTOR signaling pathway and STAT3. Oncol Rep, 2018. 40(2): p. 867-876.
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| eISSN: | 1896-9151 |
| ISSN: | 1734-1922 |
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