This study investigates the protective effect of
baicalein on
carbon tetrachloride (CCl4)-induced acute liver injury and the underlying molecular mechanisms. Mice were orally administrated
baicalein at 25 and 100 mg/kg/day for 7 consecutive days or
ferrostatin-1 (Fer-1)
at 10 mg/kg was i.p. injected in mice at 2 and 24 h prior to CCl4 injection or the vehicle. Our results showed that
baicalein or Fer-1 supplementation significantly attenuated CCl4 exposure-induced elevations of serum
alanine aminotransferase and
aspartate aminotransferase, and
malondialdehyde levels in the liver tissues and unregulated
glutathione levels.
Baicalein treatment inhibited the
nuclear factor kappa-B (NF-κB) pathway, activated the erythroid 2-related factor 2 (Nrf2)/
heme oxygenase 1 (HO-1) pathway in liver tissues, and markedly improved CCl4-induced apoptosis,
inflammation and ferroptosis in liver tissues exposed with CCl4. In vitro,
baicalein treatment improved CCl4 -induced decreases of cell viabilities and knockdown of Nrf2 and
arachidonate 12-lipoxygenase (ALOX12) genes partly abolished the protective effect of
baicalein on CCl4 -induced cytotoxicity in HepG2 cells. In conclusion, our results reveal that
baicalein supplementation ameliorates CCl4-induced acute liver injury in mice by upregulating the
antioxidant defense pathways and downregulating oxidative stress, apoptosis,
inflammation and ferroptosis, which involved the activation of Nrf2 pathway and the inhibition of ALOX12 and NF-κB pathways.