Myricetin alleviates hepatic ischemia-reperfusion injury in mice by inhibiting the inflammatory response and ferroptosis through farnesoid X receptor (FXR).

Myricetin, a key flavonoid monomer derived from bayberry fruit, exhibits antioxidant and antibacterial activities. However, its role in hepatic ischemia-reperfusion injury (HIRI) is unclear. In the present study, we found that myricetin inhibited the expression of pro-inflammatory cytokines, reduced lipid peroxidation and mitochondrial damage to inhibit ferroptosis, and alleviated HIRI. RNA sequencing showed that myricetin may be protective by regulating inflammatory responses and ferroptosis through FXR signalling. Molecular docking showed a stable binding between myricetin and FXR, and it could promote the expression and activation of FXR. In FXR knockout mice, FXR deletion attenuated the inhibitory effect of myricetin on hepatic inflammatory response and ferroptosis in mice with HIRI, and weakened its mitigating effect on hepatic injury. Collectively, these findings establish myricetin as a novel protective agent against HIRI by activating the FXR, providing experimental evidence for its potential therapeutic application in HIRI-related diseases.