Astragalin inhibits hepatitis B virus through functional reconstitution of CD8+ T cells and a direct effect on HBV control

  • Eur J Pharmacol. 2025 Aug 29:1005:178108. doi: 10.1016/j.ejphar.2025.178108.
Haohao Li  1 ,  Shasha Yang  1 ,  Huajun Zhao  1 ,  Jian Zhang  1 ,  Wei Guo  2 ,  Tao Shen  3 ,  Qiuju Han  4
Affiliations
  • 1. State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, China.
  • 2. Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250014, China. Electronic address: [email protected].
  • 3. State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, China. Electronic address: [email protected].
  • 4. State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, China. Electronic address: [email protected].
PMID: 40886877 DOI: 10.1016/j.ejphar.2025.178108
Abstract

Persistent HBV Infection promotes hepatic lipid accumulation, a feature linked to immune dysfunction. We found cytotoxic T lymphocytes (CD8+ T cells) from chronic HBV Infection (CHB) patients exhibited elevated lipid peroxidation in response to hepatic lipids accumulation. And lipid peroxidation drives CD8+ T cell dysfunction. Astragalin (AG), a natural active compound from Chinese herbs, reduced lipid peroxidation. Mechanically, AG upregulated Glutathione Peroxidase 4 (GPX4) expression, protecting CD8+ T cells against membrane lipid peroxidation and reversing their exhaustion during chronic HBV Infection. Importantly, AG significantly reduced circulating serum HBsAg and HBV DNA levels in HBV-carrier mice. Furthermore, AG directly reduced HBsAg, HBeAg and HBV RNA levels in HepG2.2.15 cells and significantly induced expression of the interferon-inducible Antiviral protein myxovirus resistance protein A (MxA). In conclusion, AG exhibits dual anti-HBV activity by enhancing CD8+ T cell Antiviral function and directly suppressing HBV replication, holding promise as a potential candidate for the treatment of chronic HBV Infection.

Keywords
Astragalin; Chronic hepatitis B; Cytotoxic T lymphocytes; Glutathione peroxidase 4; Lipid peroxidation.
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