The improvement effect of gastrodin on LPS/GalN-induced fulminant hepatitis via inhibiting inflammation and apoptosis and restoring autophagy

• Published in: International immunopharmacology 2020-08, Vol.85, p.106627, Article 106627
• Main Authors: Lv, Hongming, Liu, Yuanyuan, Zhang, Boxi, Zheng, Yuwei, Ji, Hong, Li, Shize
• Format: Article
• Language: English
• Subjects: Acetyl-CoA carboxylase; Acetyl-CoA Carboxylase - metabolism; Activation; Alanine Transaminase - blood; AMP; AMP-activated protein kinase; Animals; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Apoptosis; Apoptosis - drug effects; Aspartate Aminotransferases - blood; Autophagy; Autophagy - drug effects; Benzyl Alcohols - chemistry; Benzyl Alcohols - pharmacology; Benzyl Alcohols - therapeutic use; Caspase-3; Cytokines - metabolism; D-Galactosamine; Fulminant hepatitis; Galactosamine - toxicity; Gastrodin; Glucosides - chemistry; Glucosides - pharmacology; Glucosides - therapeutic use; Hep G2 Cells; Hepatitis; Hepatocyte apoptosis; Humans; Inflammasomes; Inflammasomes - drug effects; Inflammation; Inflammation - drug therapy; Inflammation - metabolism; Interleukin 6; Kinases; Lipopolysaccharides; Lipopolysaccharides - toxicity; Male; Massive Hepatic Necrosis - chemically induced; Massive Hepatic Necrosis - drug therapy; Mice, Inbred C57BL; NF-kappa B p50 Subunit - metabolism; NF-κB protein; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Nucleotides; p53 Protein; Peroxisome proliferator-activated receptors; Phagocytosis; Phenolic compounds; Phenols; Phosphorylation; Protein Kinases - metabolism; Proteins; Receptors; Signaling pathway; Survival; Survival Rate; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2020.106627

•GTD treatment alleviated (LPS/GalN)-induced FH in mice.•GTD treatment inhibited inflammatory reaction by inactivating NLRP3 and NF-κB pathway.•GTD treatment reduced hepatic apoptosis by regulating apoptosis-related protein PPARs, P53 and caspase-3/9.•GTD treatment restored AMPK/ACC/autophagy pathway. Fulminant hepatitis (FH), characterized by overwhelmed inflammation and massive hepatocyte apoptosis, is a life-threatening and high mortality rate. Gastrodin (GTD), a phenolic glucoside extracted from Gastrodiaelata Blume, exerts anti-apoptosis, and anti-inflammatory activities. In the present study, we aimed to evaluate whether GTD treatment could alleviate lipopolysaccharide and d-galactosamine (LPS/GalN)-induced FH in mice and its potential mechanisms. These data suggested that GTD treatment remarkably protected against LPS/GalN-induced FH by enhancing the survival rate of mice, reducing ALT and AST levels, attenuating histopathological changes, and suppressing interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α secretion. In addition, GTD treatment relieved hepatic apoptosis by the regulation of peroxisome proliferator-activated receptors (PPARs), P53 and caspase-3/9. Furthermore, GTD treatment could significantly inhibit inflammation-related signaling pathways activated by LPS/GalN, including the suppression of nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) and nuclear factor-kappa B (NF-κB) activation. Importantly, GTD treatment effectively restored but not induced LPS/GalN-reduced the expression of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation, as well as the level of pro-autophagy proteins. Taken together, our investigation indicated that GTD played an essential role in liver protection by relieving hepatocyte apoptosis and inflammation reaction, which may be closely involved in the inhibition of NLRP3 inflammasome and NF-κB activation, regulation of apoptosis-related proteins expression, and the recovery of AMPK/ACC/autophagy.