Abietic acid inhibits acetaminophen-induced liver injury by alleviating inflammation and ferroptosis through regulating Nrf2/HO-1 axis

•Abietic acid significantly ameliorated APAP-induced liver injury, TNF-α and IL-1β production.•Abietic acid significantly ameliorated APAP-induced ferroptosis.•Abietic acid could inhibit APAP-induced NF-κB activation and increase Nrf2 expression.•The inhibitory effects of abietic acid on APAP-induced liver injury were prevented in Nrf2−/− mice. Abietic acid has been known to exhibit anti-inflammatory activity. This study was designed to investigate the protective effects of abietic acid on acetaminophen (APAP)-induced liver injury. The data demonstrated that abietic acid significantly ameliorated APAP-induced liver pathological changes, TNF-α and IL-1β production. APAP could increase malondialdehyde (MDA) and Fe2+ levels, and decrease ATP and glutathione (GSH) levels, as well as glutathione peroxidase 4 (GPX4) and xCT expression. However, these changes induced by APAP were prevented by abietic acid, indicating abietic acid could inhibit APAP-induced ferroptosis. Furthermore, abietic acid inhibited APAP-induced NF-κB activation and increased the expression of Nrf2 and HO-1. Additionally, the inhibitory effects of abietic acid on APAP-induced liver injury were prevented in Nrf2-/- mice. In vitro, the inhibition of abietic acid on APAP-induced inflammation and ferroptosis were reversed when Nrf2 was knockdown. In summary, abietic acidexhibited a therapeutic effectagainst liver injury by attenuating inflammation and ferroptosis.