extract alleviated acetaminophen-induced rat liver injury via inhibiting oxidative stress and apoptosis based on network pharmacology analysis.

CONTEXT

Acetaminophen (APAP) overdose is the leading cause of drug-induced liver injury. , a variety of Ramat. (Asteraceae), has potential hepatoprotective effect. However, the mechanism is not clear yet.

OBJECTIVE

To investigate the hepatoprotective activity and mechanism of flower ethanol extract (BZE) on APAP-induced rats based on network pharmacology.

MATERIALS AND METHODS

Potential pathways of BZE were predicted by network pharmacology. Male Sprague-Dawley rats were pre-treated with BZE (110, 220 and 440 mg/kg, i.g.) for eight days, and then APAP (800 mg/kg, i.g.) was used to induce liver injury. After 24 h, serum and liver were collected for biochemical detection and western blot measurement.

RESULTS

Network pharmacology indicated that liver-protective effect of BZE was associated with its antioxidant and anti-apoptotic efficacy. APAP-induced liver pathological change was alleviated, and elevated serum AST and ALT were reduced by BZE (440 mg/kg) (from 66.45 to 22.64 U/L and from 59.59 to 17.49 U/L, respectively). BZE (440 mg/kg) reduced the ROS to 65.50%, and upregulated SOD and GSH by 212.92% and 175.38%, respectively. In addition, BZE (440 mg/kg) increased levels of p-AMPK, p-GSK3β, HO-1 and NQO1, ranging from 1.66- to 10.29-fold compared to APAP group, and promoted nuclear translocation of Nrf2. BZE also inhibited apoptosis induced by APAP through the PI3K-Akt pathway and restored the ability of mitochondrial biogenesis.

DISCUSSION AND CONCLUSIONS

Our study demonstrated that BZE protected rats from APAP-induced liver injury through antioxidant and anti-apoptotic pathways, suggesting BZE could be further developed as a potential liver-protecting agent.