Panduratin A from Boesenbergia rotunda suppresses hepatitis B virus by targeting HNF1α and synergizing with antiviral agents

TL;DR

Panduratin A, a compound from Boesenbergia rotunda, effectively suppresses hepatitis B virus by targeting HNF1α and works well with existing antiviral drugs.

Contribution

Panduratin A's anti-HBV mechanism is shown to involve HNF1α, and its synergistic potential with antiviral agents is demonstrated.

Findings

Panduratin A significantly reduced HBV DNA, HBsAg, HBeAg, and pgRNA in infected hepatocytes.

Panduratin A's antiviral effects were mediated through HNF1α, as knockdown reduced efficacy and ectopic expression restored it.

Combination with GS-5801 showed synergy, while NVR-3778 produced additive antiviral effects in HBV-infected cells.

Abstract

Boesenbergia rotunda (fingerroot) is widely used in traditional medicine, and its bioactive compound panduratin A has demonstrated potent antiviral properties. However, the mechanistic basis underlying its anti-hepatitis B virus (HBV) activity remains to be fully elucidated.

HBV-infected human hepatocytes (imHCs) were treated with B. rotunda extract, panduratin A, or pinostrobin. Intracellular HBV DNA, secreted HBsAg and HBeAg, and pregenomic RNA (pgRNA) were quantified in dose- and time-dependent experiments. Luciferase reporter assays were used to assess HBV promoter activity. The roles of HNF1α and HNF4α were evaluated by siRNA-mediated knockdown and ectopic gene expression. Drug interaction studies were performed using the KDM5 inhibitor GS-5801 and the capsid assembly modulator NVR-3778. A 3D liver spheroid model was used to validate antiviral effects on HBV DNA and cccDNA. Gene interaction network analysis was conducted to identify central regulatory pathways.

B. rotunda extract, panduratin A, and pinostrobin significantly suppressed intracellular HBV DNA, HBsAg, HBeAg, and pgRNA. Panduratin A exhibited the strongest antiviral activity and inhibited preS1, preS2, and core promoter activities. Panduratin A markedly downregulated HNF1α expression, with only modest effects on HNF4α. Knockdown of HNF1α significantly reduced the antiviral efficacy of panduratin A, whereas ectopic HNF1α expression rescued its inhibitory effects. Co-treatment with GS-5801 produced synergistic activity, and combination with NVR-3778 yielded additive antiviral effects. In 3D liver spheroids, panduratin A reduced intracellular HBV DNA and cccDNA with minimal cytotoxicity. Network analysis further identified HNF1α as a key regulatory node modulated by panduratin A.

Panduratin A is a potent anti-HBV compound that acts primarily through HNF1α-dependent suppression of HBV transcription and replication. Its efficacy in combination therapy and in 3D liver models highlights its potential as a promising candidate for future HBV treatment strategies.

The online version contains supplementary material available at 10.1186/s13020-025-01285-w.

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