The Protective Effects of Imperatorin on Acetaminophen Overdose-Induced Acute Liver Injury

Abstract

Acetaminophen (APAP) toxicity leads to severe acute liver injury (ALI) by inducing excessive oxidative stress, inflammatory response, and hepatocyte apoptosis. Imperatorin (IMP) is a furanocoumarin from Angelica dahurica, which has antioxidant and anti-inflammatory effects. However, its potential to ameliorate ALI is unknown. In this study, APAP-treated genetic knockout of Farnesoid X receptor (FXR) and Sirtuin 1 (SIRT1) mice were used for research. The results revealed that IMP could improve the severity of liver injury and inhibit the increase of proinflammatory cytokines, oxidative damage, and apoptosis induced by overdose APAP in an FXR-dependent manner. We also found that IMP enhanced the activation and translocation of FXR by increasing the expression of SIRT1 and the phosphorylation of AMPK. Besides, single administration of IMP at 4 h after APAP injection can also improve necrotic areas and serum transaminase, indicating that IMP have both preventive and therapeutic effects. Taken together, it is the first time to demonstrate that IMP exerts protective effects against APAP overdose-induced hepatotoxicity by stimulating the SIRT1-FXR pathway. These findings suggest that IMP is a potential therapeutic candidate for ALI, offering promise for the treatment of hepatotoxicity associated with APAP overdose.

Gut microbiota accelerates cisplatin-induced acute liver injury associated with robust inflammation and oxidative stress in mice

“…In particular, palmitic acid that could lead to insulin resistance by binding directly with MD2 to activate TLR4/NF-κB signal pathway [ 29 ]. Meanwhile, several potential metabolites which possess anti-inflammatory and anti-oxidation stress activities were reduced in cisplatin compared to control group [ 31 – 35 ]. It is reported that imperatorin could attenuate dextran sulphate sodium induced colitis by targeting pregnane X receptor to inhibit inflammatory response in mice [ 34 ].…”

“…It is reported that imperatorin could attenuate dextran sulphate sodium induced colitis by targeting pregnane X receptor to inhibit inflammatory response in mice [ 34 ]. In addition, prominent research efforts have elaborated that imperatorin could protect against drug induced liver injury associated with decrease level of inflammation cytokines and oxidative stress in mice [ 35 ]. We mapped metabolites to physiological pathways and observed significant differences in the levels of several pathways responsible for metabolism.…”

Cinnamon oil against acetaminophen-induced acute liver toxicity by attenuating inflammation, oxidative stress and apoptosis

“…Nevertheless, long term administration or overdoses of APAP can cause a deleterious effect on the liver [ 6 ]. APAP-induced liver injury was well recognized by numerous studies- [ [7] , [8] , [9] ].…”

Hepatoprotective Effect and Molecular Mechanisms of Hengshun Aromatic Vinegar on Non-Alcoholic Fatty Liver Disease

“…Celastrol has a protective effect on cholestatic liver injury by regulating SIRT1/FXR pathway (Zhao et al, 2019). Other research revealed that imperatorin exerts the protective effect against hepatotoxicity induced by excessive acetaminophen similarly by stimulating the SIRT1/FXR pathway (Gao et al, 2020). Moreover, studies have showed that NAFLD may be mitigated through the regulation of SIRT1/FXR signaling pathway (Han et al, 2019).…”