Published online Feb 21, 2021. doi: 10.3748/wjg.v27.i7.592
Peer-review started: October 26, 2020
First decision: November 25, 2020
Revised: November 30, 2020
Accepted: January 21, 2021
Article in press: January 21, 2021
Published online: February 21, 2021
Sinapic acid (SA) has been shown to have various pharmacological properties such as antioxidant, antifibrotic, anti-inflammatory, and anticancer activities. Its mechanism of action is dependent upon its ability to curb free radical production and protect against oxidative stress-induced tissue injuries.
To study the hepatoprotective effects of SA against lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute liver failure (ALF) in rats.
Experimental ALF was induced with an intraperitoneal (i.p.) administration of 8 μg LPS and 800 mg/kg D-GalN in normal saline. SA was administered orally once daily starting 7 d before LPS/D-GalN treatment.
Data showed that SA ameliorates acute liver dysfunction, decreases serum levels of alanine transaminase (ALT), and aspartate aminotransferase (AST), as well as malondialdehyde (MDA) and NO levels in ALF model rats. However, pretreatment with SA (20 mg/kg and 40 mg/kg) reduced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and levels of inflammatory cytokines (tumor necrosis factor-α and interleukin 6). Also, SA increased the activity of the nuclear factor erythroid-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway.
In conclusion, SA offers significant protection against LPS/D-GalN-induced ALF in rats by upregulating Nrf2/HO-1 and downregulating NF-κB.
Core Tip: This work demonstrated for the first time that the sinapic acid (SA) has hepatoprotective effects in the D-galactosamine/lipopolysaccharide (D-GalN/LPS)-induced rat model through its ability to suppress oxidative stress, inflammation, and apoptosis. The protective mechanism of SA depends on the downregulation of nuclear factor kappa-light-chain-enhancer of activated B cells and the restoration of antioxidant enzyme levels through the activation of the Nrf2/HO-1 pathway. Thus, SA could be applied to treat or prevent D-GalN/LPS-induced acute liver failure in the future.