Baicalein protects against polymicrobial sepsis-induced liver injury via inhibition of inflammation and apoptosis in mice.

Abstract

Liver dysfunction has been known to occur frequently in cases of sepsis. Baicalein, the main active ingredient of the Scutellaria root, exerts anti-inflammatory and anti-apoptotic properties in endotoxic shock. However, the role of baicalein in polymicrobial sepsis-induced liver injury and its regulatory mechanisms remain unclear. In this study, we aimed to investigate the protective effects of baicalein on polymicrobial sepsis-induced liver injury and to explore the possible mechanisms. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in C57BL/6 mice. Mice were treated with baicalein (100mg/kg, i.p) at 1h, 6h and 12h following CLP. Baicalein significantly improved the survival of septic mice. Treatment with baicalein ameliorated the CLP-induced liver injury, as indicated by the lower serum aminotransferase levels and the fewer histopathologic abnormalities. Baicalein reduced the neutrophil infiltration and the hepatic inflammatory cytokine expression and release. It also decreased the hepatic and the serum high-mobility group box 1 and macrophage migration inhibitory factor levels in septic mice. Moreover, baicalein significantly inhibited the mitogen-activated protein kinases (MAPKs) activation and suppressed the transcriptional activity of nuclear factor-kappa B (NF-κB). In conclusion, these results suggest that baicalein treatment could protect against the sepsis-induced liver injury, and improve the survival of mice with polymicrobial sepsis. The mechanism of the protective action of baicalein seems to involve its ability to reduce inflammatory response, to inhibit hepatic apoptosis, and to suppress MAPKs and NF-κB activation.

• Authors: Anding Liu, Wenjie Wang, Haoshu Fang, Yan Yang, Xiaojing Jiang, Shenpei Liu, Jifa Hu, Qi Hu, Uta Dahmen, Olaf Dirsch
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 748 Pg. 45-53 (Feb 05 2015) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 25533331 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Flavanones
• HMGB1 Protein
• Inflammation Mediators
• Macrophage Migration-Inhibitory Factors
• Protective Agents
• baicalein
• Intramolecular Oxidoreductases
• Mif protein, mouse

Topics

• Animals
• Apoptosis (drug effects)
• Cecum (surgery)
• Flavanones (pharmacology, therapeutic use)
• Gene Expression Regulation (drug effects)
• HMGB1 Protein (metabolism)
• Inflammation (drug therapy)
• Inflammation Mediators (metabolism)
• Intramolecular Oxidoreductases (metabolism)
• Ligation (adverse effects)
• Liver (drug effects, immunology, injuries, pathology)
• Macrophage Migration-Inhibitory Factors (metabolism)
• Male
• Mice
• Neutrophil Infiltration (drug effects)
• Protective Agents (pharmacology, therapeutic use)
• Punctures (adverse effects)
• Sepsis (complications, etiology, microbiology)
• Signal Transduction (drug effects)