2. Academic Validation
  3. Baicalein inhibits hepatitis B virus through the coiled coil domain containing protein 88A (CCDC88A)-dependent autophagy pathway

Baicalein inhibits hepatitis B virus through the coiled coil domain containing protein 88A (CCDC88A)-dependent autophagy pathway

  • Phytomedicine. 2025 May:140:156577. doi: 10.1016/j.phymed.2025.156577.
Yi-Jun Niu 1,  Xin Ai 1,  Xiao-Tong Lin 1,  Wei-Ming Xu 1,  Su-Ya Lao 1,  Zi-Chen Tian 1,  Hai-Yan Zhu 1,  Wei Zhou 2,  Hai Huang 1,  Xun-Long Shi 3
Affiliations

Affiliations

  • 1 Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics, Fudan University School of Pharmacy, Shanghai 201203, , PR China.
  • 2 Department of Chemistry, Fudan University, 220 Han Dan Road, Shanghai 200433, China.
  • 3 Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics, Fudan University School of Pharmacy, Shanghai 201203, , PR China. Electronic address: xunlongshi@fudan.edu.cn.
PMID: 40023973 DOI: 10.1016/j.phymed.2025.156577
Abstract

Background: Chronic Infection with the hepatitis B virus (HBV) represents a significant global health concern. Baicalein, a naturally occurring flavone derived from the roots of Scutellaria baicalensis Georgi, has exhibited both anti-inflammatory and Antiviral activities. S. baicalensis is extensively utilized in traditional Chinese medicine for the treatment of various liver disorders, including hepatitis. However, the specific anti-HBV effects of baicalein have not been fully elucidated.

Purpose: This study aimed to investigate the inhibitory effects of baicalein on HBV and to elucidate its underlying mechanisms.

Materials and methods: The levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were measured using enzyme-linked immunosorbent assay (ELISA) kits. Quantification of HBV DNA was performed using quantitative real-time polymerase chain reaction (qRT-PCR). Western blot analysis was conducted to evaluate proteins involved in Autophagy, lysosomal acidification, and autophagy-related signaling pathways. Immunofluorescence microscopy was utilized to assess autophagic flux and lysosomal acidification.

Results: Baicalein demonstrated significant inhibition of HBsAg, HBeAg, and HBV-DNA secretion in both in vivo and in vitro environments. Subsequent investigations revealed that baicalein disrupted the intracellular trafficking of the hepatitis B virus by inhibiting the CCDC88A-AKT-mTOR (Coiled coil domain containing protein 88A- protein kinase B-mammalian target of rapamycin) signaling pathway. Additionally, baicalein induced Autophagy in HepG2 (Human hepatocellular carcinoma cell line 2) and HepG2.215 cell models. The anti-hepatitis B antigen effect of baicalein was partially attenuated when both early and late stages of Autophagy were inhibited. A significant correlation was identified between the phosphorylation of AMPKα and the enhanced Autophagy observed in baicalein-treated cells.

Conclusions: This study elucidates a novel mechanism by which baicalein inhibits the hepatitis B virus (HBV). Specifically, baicalein exerts its Antiviral effects by activating Autophagy and suppressing the CCDC88A-AKT-mTOR signaling pathway.

Keywords

AMPKα; Autophagy; Baicalein; CCDC88A; Hepatitis B virus.

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