Pterostilbene Protects Against Lipopolysaccharide/D-Galactosamine-Induced Acute Liver Failure by Upregulating the Nrf2 Pathway and Inhibiting NF-κB, MAPK, and NLRP3 Inflammasome Activation.

The purpose of this study was to evaluate the protective effect of pterostilbene (Psb) against lipopolysaccharide and D-galactosamine (L/D)-induced acute liver failure (ALF) in mice and its potential mechanisms. Histology of liver was detected by H&E staining. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in serum and malondialdehyde (MDA), myeloperoxidase (MPO), glutathione (GSH), and superoxide dismutase (SOD) contents in liver were examined using detection kits. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) secretion were detected by ELISA. Meanwhile, MAPK, NF-κB, NLRP3 inflammasome, and Nrf2 were assessed by western blotting. Our findings showed that pretreatment with Psb protected against L/D-induced ALF by lowering the lethality, improving liver histology, reducing ALT, AST, IL-6, IL-1ß, TNF-α, MDA, and MPO levels, and boosting liver GSH content and SOD activity. Moreover, Psb pretreatment effectively suppressed inflammation by decreasing NLRP3 inflammasome, MAPK, and NF-κB pathway activations. Moreover, Psb pretreatment efficiently enhanced the expression of several antioxidant enzymes, mainly depending on Nrf2 activation. This was the first study to demonstrate that Psb protects against L/D-induced ALF by inactivating MAPK, NF-κb, and NLRP3 inflammasome and upregulating the Nrf2 signaling pathway, indicating a potential therapeutic application for ALF treatment.