Paeoniflorin ameliorates lipopolysaccharide-induced acute liver injury by inhibiting oxidative stress and inflammation via SIRT1/FOXO1a/SOD2 signaling in rats.

Abstract

Acute liver injury (ALI) is a poor prognosis and high mortality complication of sepsis. Paeoniflorin (PF) has remarkable anti-inflammatory effects in different disease models. Here, we explored the protective effect and underlying molecular mechanisms of PF against lipopolysaccharide (LPS)-induced ALI. Sprague-Dawley rats received intraperitoneal (i.p.) injection of PF for 7 days, 1 h after the last administration, and rats were injected i.p. 10 mg/kg LPS. PF improved liver structure and function, reduced hepatic reactive oxygen species (ROS) and methane dicarboxylic aldehyde (MDA) levels, and increased superoxide dismutase (SOD) activity. Western blot analysis suggested that PF significantly inhibited expression of inflammatory cytokines (TNF-α, IL-1β, and IL-18) and inhibited activation of the NLRP3 inflammasome. PF or mitochondrial ROS scavenger (mito-TEMPO) significantly improved liver mitochondrial function by scavenging mitochondrial ROS (mROS), restoring mitochondrial membrane potential loss and increasing level of ATP and enzyme activity of complex I and III. In addition, PF increased expression of sirtuin-1 (SIRT1), forkhead box O1 (FOXO1a) and manganese superoxide dismutase (SOD2), and increased FOXO1a nuclear retention. However, the inhibitor of SIRT1 (EX527) abolished the protective effect of PF. Taken together, PF promotes mROS clearance to inhibit mitochondrial damage and activation of the NLRP3 inflammasome via SIRT1/FOXO1a/SOD2 signaling.

• Authors: Lin Li, Hui Wang, Shuping Zhao, Yuan Zhao, Yongping Chen, Jiuyan Zhang, Chuqiao Wang, Ning Sun, Honggang Fan
• Journal: Phytotherapy research : PTR (Phytother Res) Vol. 36 Issue 6 Pg. 2558-2571 (Jun 2022) ISSN: 1099-1573 [Electronic] England
• PMID: 35570830 (Publication Type: Journal Article)
• Copyright: © 2022 John Wiley & Sons Ltd.

Chemical References

• Glucosides
• Inflammasomes
• Lipopolysaccharides
• Monoterpenes
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nerve Tissue Proteins
• Reactive Oxygen Species
• Foxo1 protein, rat
• peoniflorin
• Superoxide Dismutase
• superoxide dismutase 2
• Sirt1 protein, rat
• Sirtuin 1

Topics

• Animals
• Chemical and Drug Induced Liver Injury (drug therapy)
• Glucosides (pharmacology)
• Inflammasomes (metabolism)
• Inflammation (drug therapy, metabolism)
• Lipopolysaccharides
• Liver (metabolism)
• Monoterpenes (pharmacology)
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Nerve Tissue Proteins (metabolism)
• Oxidative Stress
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Signal Transduction
• Sirtuin 1 (metabolism)
• Superoxide Dismutase (metabolism)