Research Paper Volume 16, Issue 15 pp 11668—11682
Solamargine acts as an antiviral by interacting to MZF1 and targeting the core promoter of the hepatitis B virus gene
- 1 Department of Gastroenterology, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, Henan 450003, China
- 2 Master of Chinese medicine (studies and applications of internal Chinese medicines), Hong Kong Baptist University, Kowloon Tong, Hong Kong
- 3 Xinxiang Medical University, Clinical Medicine College, Xinxiang, Henan 453000, China
- 4 The Third Affiliated Hospital Affiliated of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan 450003, China
Received: December 15, 2023 Accepted: July 5, 2024 Published: August 10, 2024
https://doi.org/10.18632/aging.206047How to Cite
Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Hepatitis B virus (HBV) infection is still a serious threat to global health and can lead to a variety of liver diseases, including acute and chronic hepatitis, liver cirrhosis, liver failure, hepatocellular carcinoma (HCC), and so on. At present, there are mainly two kinds of drugs for the treatment of hepatitis B at home and abroad: interferon (IFN) and nucleoside/nucleotide analogs (NAs). In recent years, natural compounds have been considered an important source for the development of new anti-HBV drugs due to their complex structure, diverse components, high efficiency, and low toxicity. Many studies have demonstrated that Solamargine has significant anticancer activity, but the antiviral effect is rarely studied. This study aimed to verify the anti-HBV effect of Solamargine and to explore the specific mechanism.
Method: The relative expression of HBV pregenomic RNA (pgRNA) was detected by reverse transcription real-time fluorescence quantitative PCR (RT-qPCR). Northern blot and western blot were used to detect the relative expression of HBV pgRNA and target protein. PCR was used in the construction of HBV pg-promoter, ENII/BCP, and a series of gene deletion mutant fluorescent reporter vectors. The fluorescence relative expression of each mutant was detected by Renilla luciferase assay.
Results: By binding to MZF1 (Myeloid zinc finger protein 1, MZF1), Solamargine inhibits HBV core promoter activity, reduces pregenomic RNA level, and inhibits HBV, achieving antiviral effects.
Abbreviations
HBV: hepatitis B virus; cccDNA: covalently closed circular DNA; IFN-α: interferon-α; HBx: hepatitis B virusX; pgRNA: pregenomic RNA; HBeAg: Hepatitis B virus antigen; rcDNA: relaxed circular DNA; HBc: Hepatitis B virus core; HBs: Hepatitis B virus surface; MZF1: Myeloid zinc finger protein 1; ESRRA: Estrogen related receptor alpha; NR4A1: nuclear receptor subfamily 4, group A, member 1; GATA3: GATA-binding protein 3; TEF: Transcriptional Enhancer Factor; NR1I3: nuclear receptor subfamily 1 group I member 3; NFIL3: nuclear receptor subfamily 1 group I member 3.