Inhibition of hepatitis B virus through PPAR-JAK/STAT pathway modulation by electroacupuncture and tenofovir disoproxil fumarate combination therapy.

BACKGROUND

Acupuncture combined with nucleos(t)ide analogues (NAs) has shown promise in treating chronic hepatitis B (CHB), though mechanisms remain unclear. This study evaluates the antiviral effects of combining acupuncture with NAs against hepatitis B virus (HBV) and explores underlying mechanisms.

METHODS

The HBV-infected mouse model, established using the high-pressure hydrodynamic method, was divided into three groups: normal saline (NS), tenofovir disoproxil fumarate (TF), and electroacupuncture combined with TF (E_T), n = 6. Antiviral effects were assessed by monitoring HBV DNA, HBsAg, and HBeAg levels weekly. Mechanistic insights were gained via transcriptomics, metabolomics, and 16S rDNA sequencing, validated by WB, PCR, and flow cytometry.

RESULTS

Serum HBV DNA levels decreased by 1.98 log10 IU/mL in TF and 2.2 log10 IU/mL in E_T groups compared to NS. Serum HBeAg decreased by 10.61 % in TF and 35.75 % in E_T, while HBsAg decreased by 7.38 % and 37.58 %, respectively. Multi-omics indicated E_T modulates the PPAR pathway, upregulates taurine and all-trans-retinoic acid, and increases gut microbiota like Bacteroides and Blautia. E_T also enhanced tight junction proteins (ZO-1, Occludin, Claudin-4), improving intestinal barrier integrity. Mechanistically, E_T inhibited the PGC-1α/PPAR-α/SIRT1 pathway, reducing PGC-1α, PPAR-α, SIRT1, RXRα, and HNF4α, while promoting JAK/STAT signaling via IFN-γ, p-JAK1, p-JAK2, p-STAT1, IRF8, and suppressing SOCS-1.

CONCLUSION

E_T more effectively inhibited HBV replication, showing superior antigen inhibition, particularly HBsAg, than TF alone. This may be due to PPAR-JAK/STAT pathway regulation, suggesting E_T as a potential adjuvant therapy for CHB, especially in achieving a functional cure.