Protective effects of emodin combined with danshensu on experimental severe acute pancreatitis.
OBJECTIVE
In the present experiment, we aimed to determine the feasibility and curative effects of emodin combined with danshensu on experimental severe acute pancreatitis (SAP) and the mutual benefit of this synergistic strategy by a prospective animal study.


METHODS
Eighty Wistar rats were randomly divided into four groups (n = 20).


METHODS
SAP was elicited by a retrograde infusion of 5.0% sodium taurocholate into the pancreatic main duct. SAP rats in each group received no further intervention, emodin alone, danshensu (DSS) alone, and emodin combined with DSS (EDSS), respectively.


METHODS
48 h after SAP induction, all surviving animals were sacrificed to collect blood and tissue samples for the following measurements: serum levels of amylase, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), endotoxin and D-lactate. Pancreatic levels of TNF-alpha, IL-1beta, maleic dialdehyde (MDA), myeloperoxidase (MPO) activity, nuclear factor-kappaappaB (NF-kappaB) activation as well as wet-dry weight ratio were also evaluated. Ascitic fluid was quantified and the severity of pancreatic damage was analyzed by pathological grading and scoring.


RESULTS
Compared with the SAP group, the emodin, DSS and EDSS groups had significant differences in every index. Furthermore, EDSS obviously improved all the parameters mentioned above so as to counteract inflammatory response and oxidative stress, as well as most effectively abating pancreatic and intestinal barrier injury.


CONCLUSIONS
EDSS exerted protective effects on SAP rats and remarkably alleviated the severity of experimental SAP. Mechanisms that might account for the beneficial effects include protecting the intestinal barrier, inhibiting over-inflammatory reaction and abating oxidative stress. The combined strategy proved to be more effective than either emodin or DSS alone and may cause synergistic effects in combination in the early stage of SAP. Broad potential for future clinical practice is foreseeable.
Wang
Gang
G
Department of Hepatobiliary Pancreatic Surgery, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng St, Nangang Dist 150001, Harbin, Heilongjiang, People's Republic of China. wgilu79@yahoo.com.cn
Sun
Bei
B
Zhu
Hong
H
Gao
Yue
Y
Li
Xiurong
X
Xue
Dongbo
D
Jiang
Hongchi
H
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D001202:Ascitic Fluid / Q000187:drug effects; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use; D004487:Edema / Q000473:pathology; D004642:Emodin / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000378:metabolism; D007773:Lactates / Q000627:therapeutic use*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000447:Aldehydes; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D053583:Interleukin-1beta; D007773:Lactates; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C015977:malealdehyde; C035055:3,4-dihydroxyphenyllactic acid; D009195:Peroxidase; D004642:Emodin