Tetramethylpyrazine ameliorates sepsis-induced liver injury via inhibiting ferroptosis

Sepsis often leads to multi-organ dysfunction, with liver injury being a serious complication. Ferroptosis, an iron-dependent cell death, is closely linked to sepsis-related organ damage. Tetramethylpyrazine (TMP), a traditional Chinese medicine component, exhibits anti-inflammatory and antioxidant properties. To elucidate its role in Ferroptosis of sepsis-induced liver injury, we established murine sepsis models via cecum ligation and puncture (CLP) and conducted comprehensive analyses.. Histopathological staining revealed TMP significantly attenuated liver damage and fibrosis, while biochemical assays demonstrated reduced serum inflammatory markers and liver Enzymes. Mechanistically, network pharmacology identified PPAR signaling pathway and Calcium signaling pathway as key pathways and qRT-PCR confirmed TMP suppressed ferroptosis-associated genes (TFR1, Atf3) while enhancing protective factors (GPX4, Nrf2, FSP1). Critically, in vitro studies using LPS-induced hepatocytes validated that TMP's effects were mediated through Ferroptosis inhibition. Collectively, our findings demonstrate TMP ameliorates sepsis-induced liver injury by modulating histopathological damage, fibrosis, and ferroptosis-related molecular networks, providing a novel therapeutic strategy.

Ferroptosis; GPX4/Nrf2/FSP1; Liver injury; Sepsis; Tetramethylpyrazine.