Protocatechuic aldehyde protects against experimental sepsis in vitro and in vivo.

Abstract

Recent studies have demonstrated that nuclear factor-κB (NF-κB) and high-mobility group box 1 (HMGB1) are associated with the pathophysiology of sepsis. The present study was carried out to investigate the effects of protocatechuic aldehyde (PA) on an experimental model of sepsis induced by caecal ligation and puncture (CLP) in rats and to elucidate the potential mechanism in the cultured murine macrophage cell line, RAW264.7 cells. Treatment of RAW 264.7 cells with PA blocked TNF-α-induced NF-κB phosphorylation and decreased HMGB1 expression. Septic rats received doses of 50 mg of PA alone or plus Imipenem by intravenous bolus injection into the tail vein. The results showed that PA reduced serum levels of HMGB1 and triggering the receptor expressed on myeloid cells, it attenuated myeloperoxidase in the lung, liver and small intestine, while it up-regulated serum level of IL-10. Meanwhile, PA alone or plus Imipenem reduced CLP-induced lethality in septic rats. These data indicate that the anti-septic effect of PA is mediated by decreasing local and systemic levels of a wide spectrum of inflammatory mediators. The protective effects of PA might block the inflammatory cascades through HMGB1 and NF-κB signalling pathway. Our studies enhance the case for the use of PA in sepsis, and PA therefore seems promising in the treatment of sepsis in human beings.

• Authors: Yong Xu, Wang-Lin Jiang, Shu-Ping Zhang, Hai-Bo Zhu, Jian Hou
• Journal: Basic & clinical pharmacology & toxicology (Basic Clin Pharmacol Toxicol) Vol. 110 Issue 4 Pg. 384-9 (Apr 2012) ISSN: 1742-7843 [Electronic] England
• PMID: 22050905 (Publication Type: Journal Article)
• Copyright: © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

Chemical References

• Anti-Bacterial Agents
• Benzaldehydes
• Catechols
• HMGB1 Protein
• Inflammation Mediators
• NF-kappa B
• Tumor Necrosis Factor-alpha
• Interleukin-10
• protocatechualdehyde
• Imipenem

Topics

• Animals
• Anti-Bacterial Agents (administration & dosage, pharmacology)
• Benzaldehydes (administration & dosage, pharmacology)
• Catechols (administration & dosage, pharmacology)
• Cell Line
• Disease Models, Animal
• Drug Therapy, Combination
• HMGB1 Protein (genetics)
• Imipenem (administration & dosage, pharmacology)
• Inflammation (drug therapy, physiopathology)
• Inflammation Mediators (metabolism)
• Injections, Intravenous
• Interleukin-10 (blood)
• Macrophages (drug effects, metabolism)
• Male
• NF-kappa B (metabolism)
• Phosphorylation (drug effects)
• Rats
• Rats, Sprague-Dawley
• Sepsis (drug therapy, physiopathology)
• Tumor Necrosis Factor-alpha (administration & dosage)