Artesunate ameliorates severe acute pancreatitis (SAP) in rats by inhibiting expression of pro-inflammatory cytokines and Toll-like receptor 4.
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.
Department of Pharmacology, College of Pharmacy, The Third Military Medical University, Chongqing 400038, China.
Yanyan
Y
Cen
Department of Pharmacology, College of Pharmacy, The Third Military Medical University, Chongqing 400038, China.
Chao
C
Liu
Department of Pharmacology, College of Pharmacy, The Third Military Medical University, Chongqing 400038, China.
Xiaoli
X
Li
Department of Pharmacology, College of Pharmacy, The Third Military Medical University, Chongqing 400038, China.
Zifei
Z
Yan
Department of Pharmacology, College of Pharmacy, The Third Military Medical University, Chongqing 400038, China.
Mei
M
Kuang
Department of Pharmacology, College of Pharmacy, The Third Military Medical University, Chongqing 400038, China.
Yujie
Y
Su
Department of Pharmacology, College of Pharmacy, The Third Military Medical University, Chongqing 400038, China.
Xichun
X
Pan
Department of Pharmacology, College of Pharmacy, The Third Military Medical University, Chongqing 400038, China.
Rongxin
R
Qin
Medical Research Center, Southwestern Hospital, The Third Military Medical University, Chongqing 400038, China.
Xin
X
Liu
Medical Research Center, Southwestern Hospital, The Third Military Medical University, Chongqing 400038, China.
Jiang
J
Zheng
Department of Pharmacology, College of Pharmacy, The Third Military Medical University, Chongqing 400038, China. Electronic address: zhouh64@163.com.
Hong
H
Zhou
D061354:Acinar Cells / Q000187:drug effects* / Q000502:physiology; D000208:Acute Disease; D000818:Animals; D031172:Artemisia annua / Q000276:immunology*; D037621:Artemisinins / Q000627:therapeutic use*; D000077332:Artesunate; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010179:Pancreas / Q000473:pathology*; D010195:Pancreatitis / Q000188:drug therapy* / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013656:Taurocholic Acid / Q000627:therapeutic use; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
D037621:Artemisinins; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D013656:Taurocholic Acid; D000077332:Artesunate
Artesunate; IL-1β; IL-6; NF-κB; Severe acute pancreatitis; TLR4