[Total flavonoids of alleviate acetaminophen-induced acute liver injury in mice by suppressing hepatocyte ferroptosis activating the Nrf2/HO-1 signaling pathway].

OBJECTIVE

To investigate the protective effect of total flavonoids of extract against acetaminophen (APAP) -induced acute liver injury (ALI) and its molecular mechanism.

METHODS

The main chemical constituents of total flavonoids of were obtained through literature search, and their pharmacological mechanisms were predicted using bioinformatics analysis. In a mouse model of APAP-induced ALI, the protective effects of 100, 200 and 400 mg/kg total flavonoids of and 150 mg/kg bifidus were evaluated by observing changes in blood biochemistry and liver histopathology and detecting expressions of the key proteins in the Nrf2/HO-1 signaling pathway.

RESULTS

Network pharmacology analysis suggested that the main active components in total flavonoids of for regulating APAPinduced liver injury included quercetin, lignocerol, caruric acid, and kaempferol, for which GO function enrichment analysis yielded 632 GO entries, including 472 involving biological processes, 42 involving cellular composition, and 118 involving molecular function. KEGG enrichment analysis showed that the total flavonoids of regulated APAP-induced liver injury mainly through ferroptosis-related signaling pathway. In mice with APAP-induced ALI, treatment with the total flavonoids significantly lowered ALT and AST levels, improved liver histopathology and inflammatory cell infiltration, reduced iron deposition in liver tissues, improved lipid peroxidation-related indexes, promoted the expressions of Nrf2, HO-1, SLC7A11, and GPX-4 proteins, and inhibited the expression of keap1 protein.

CONCLUSION

The total flavonoids of alleviate APAP-induced ALI in mice possibly by suppressing hepatocyte ferroptosis via activating the Nrf2/SLC7A11/GPX-4 signaling pathway.