Investigating the hepatoprotective effects of Lonicera confusa against acetaminophen-induced acute liver injury: a systematic pharmacological approach

Acetaminophen (APAP) overdose frequently leads to acute liver injury (ALI), driven by oxidative stress and inflammation from toxic metabolites. Current treatments like N-acetylcysteine have a narrow therapeutic window, highlighting the need for novel herbal alternatives. This study investigated the hepatoprotective mechanisms of Lonicera confusa (SYH) against APAP-induced ALI using an integrated network pharmacology and molecular docking approach. We identified 33 active compounds and 55 potential targets. Protein-protein interaction analysis revealed five core targets: IL6, TNF, EGFR, CASP3, and TLR4. Enrichment analyses indicated SYH modulates key pathways related to oxidative stress and inflammation, including PI3K-AKT, NF-κB, and TNF pathways. Through molecular docking, strong binding affinities were confirmed, and apigetrin exhibited high affinity for the core targets. Subsequent in vivo validation demonstrated that apigetrin effectively alleviated APAP-induced ALI and inflammatory responses in mice. Collectively, these results suggest SYH mitigates ALI by inhibiting the pro-inflammatory TLR4/MYD88/NF-κB pathway and activating the antioxidant Keap-1/Nrf2/HO-1/NQO1 pathway.