Artesunate ameliorates severe acute pancreatitis (SAP) in rats by inhibiting expression of pro-inflammatory cytokines and Toll-like receptor 4.

Abstract

Severe acute pancreatitis (SAP) is a severe clinical condition with significant morbidity and mortality. Multiple organs dysfunction (MOD) is the leading cause of SAP-related death. The over-release of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α is the underlying mechanism of MOD; however, there is no effective agent against the inflammation. Herein, artesunate (AS) was found to increase the survival of SAP rats significantly when injected with 3.5% sodium taurocholate into the biliopancreatic duct in a retrograde direction, improving their pancreatic pathology and decreasing serum amylase and pancreatic lipase activities along with substantially reduced pancreatic IL-1β and IL-6 release. In vitro, AS-pretreatment strongly inhibited IL-1β and IL-6 release and their mRNA expressions in the pancreatic acinar cells treated with lipopolysaccharide (LPS) but exerted little effect on TNF-α release. Additionally, AS reduced the mRNA expressions of Toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) p65 as well as their protein expressions in the pancreatic acinar cells. In conclusion, our results demonstrated that AS could significantly protect SAP rats, and this protection was related to the reduction of digestive enzyme activities and pro-inflammatory cytokine expressions via inhibition of TLR4/NF-κB signaling pathway. Therefore, AS may be considered as a potential therapeutic agent against SAP.

• Authors: Yanyan Cen, Chao Liu, Xiaoli Li, Zifei Yan, Mei Kuang, Yujie Su, Xichun Pan, Rongxin Qin, Xin Liu, Jiang Zheng, Hong Zhou
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 38 Pg. 252-60 (Sep 2016) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 27318790 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical References

• Artemisinins
• Cytokines
• Inflammation Mediators
• NF-kappa B
• Toll-Like Receptor 4
• Taurocholic Acid
• Artesunate

Topics

• Acinar Cells (drug effects, physiology)
• Acute Disease
• Animals
• Artemisia annua (immunology)
• Artemisinins (therapeutic use)
• Artesunate
• Cells, Cultured
• Cytokines (metabolism)
• Inflammation (metabolism)
• Inflammation Mediators (metabolism)
• Male
• NF-kappa B (genetics, metabolism)
• Pancreas (pathology)
• Pancreatitis (drug therapy, immunology)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Taurocholic Acid (therapeutic use)
• Toll-Like Receptor 4 (genetics, metabolism)