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Dihydromyricetin inhibits Hepatitis B virus replication by activating NF-κB, MAPKs, and autophagy in HepG2.2.15 cells

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Abstract

Background

Hepatitis B virus (HBV) infection is a severe global health problem, and there has been no effective method to eliminate HBV. This study was designed to explore the pharmacological mechanism of Dihydromyricetin (DHM) treatment on HBV replication in vitro.

Methods and Results

DHM is a flavonoid compound from Ampelopsis grossedentata. Using HepG2.2.15 cells, which can stably express HBV in vitro, we demonstrated that DHM treatment dramatically reduced HBV replication and secretions of HBsAg and HBeAg. Meanwhile, DHM inhibited mRNA expression of HBV RNAs in HepG2.2.15 cells, including Total HBV RNA, HBV pregenomic RNA (pgRNA), and HBV precore mRNA (pcRNA). Also, DHM elevated the mRNA expressions of inflammatory cytokines and antiviral effectors. In contrast, DHM decreased the mRNA level of HNF4α, which positively correlated with HBV replication. Further studies show that the activation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathway played a critical role in DHM-initiated inhibition of HBV replication in HepG2.2.15 cells. Besides, activated autophagy was another contributor that may accelerate the clearance of HBV components.

Conclusion

In summary, DHM could suppress HBV replication by activating NF-κB, MAPKs, and autophagy in HepG2.2.15 cells. Our studies shed light on the future application of DHM for the clinical treatment of HBV infection.

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Abbreviations

HBV:

Hepatitis B virus.

DHM:

Dihydromyricetin.

rcDNA:

double-stranded relaxed circular DNA.

cccDNA:

covalently closed circular DNA.

pgRNA:

HBV pregenomic RNA.

pcRNA:

HBV precore mRNA.

NF-κB:

Nuclear factor-kappa B.

MAPK:

Mitogen-activated protein kinase.

IFN:

Interferon.

OAS:

2’,5’-oligoadenylate synthetase.

MxA:

Myxovirus resistance A protein.

PKR:

Protein kinase R.

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Authors and Affiliations

  1. College of Basic Medical Sciences, Hubei University of Chinese Medicine, Huangjiahu West Road 16, 430065, Wuhan, PR China

    Xuefeng Wang, Haiming Hu, Baifei Hu, Hui Xia, Xue Cheng, Junping Zheng, Zhigang Zhang & Hongtao Liu

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Wang, X., Hu, H., Hu, B. et al. Dihydromyricetin inhibits Hepatitis B virus replication by activating NF-κB, MAPKs, and autophagy in HepG2.2.15 cells. Mol Biol Rep 50, 1403–1414 (2023). https://doi.org/10.1007/s11033-022-07971-4

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