Abstract
Objective and design
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.
Material
Eighty Wistar rats were randomly divided into four groups (n = 20).
Treatment
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-α), interleukin-1beta (IL-1β), endotoxin and D-lactate. Pancreatic levels of TNF-α, IL-1β, maleic dialdehyde (MDA), myeloperoxidase (MPO) activity, nuclear factor-κappaB (NF-κB) 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.
Similar content being viewed by others
References
Wilmer AP. What’s new in the management of acute pancreatitis? Curr Opin Anaesthesiol. 2001;14:137–41.
Zhou ZG, Zheng YC, Shu Y, Hu WM, Tian BL, Li QS, et al. Laparoscopic management of severe acute pancreatitis. Pancreas. 2003;27:e46–50.
Granger J, Remick D. Acute pancreatitis: models, markers, and mediators. Shock. 2005;24:45–51.
Van Acker GJ, Perides G, Weiss ER, Das S, Tsichlis PN, Steer ML. Tumor progression locus-2 is a critical regulator of pancreatic and lung inflammation during acute pancreatitis. J Biol Chem. 2007;282:22140–9.
Wang G, Sun B, Gao Y, Meng QH, Jiang HC. An experimental study of emodin assisted early enteral nutrition for the treatment of severe acute pancreatitis. Hepatogastroenterology. 2008;55:33–40.
Zhang XP, Shi Y, Zhang L. Progress in the study of therapeutic effects of traditional Chinese medicine and extracts in treating severe acute pancreatitis. JOP. 2007;8:704–14.
Gong Z, Yuan Y, Lou K, Tu S, Zhai Z, Xu J. Mechanisms of Chinese herb emodin and somatostatin analogs on pancreatic regeneration in acute pancreatitis in rats. Pancreas. 2002;25:154–60.
Wu JX, Xu JY, Yuan YZ. Effects and mechanism of emodin and sandostatin on pancreatic ischemia in acute haemorrhagic necrotizing pancreatitis. Zhongguo Zhong Xi Yi Jie He Za Zhi. 1997;17:356–9.
Zhang XP, Li ZF, Liu XG, Wu YT, Wang JX, Wang KM, et al. Effects of emodin and baicalein on rats with severe acute pancreatitis. World J Gastroenterol. 2005;11:2095–100.
Wu JX, Xu JY, Yuan YZ. Effect of emodin and sandostatin on metabolism of eicosanoids in acute necrotizing pancreatitis. World J Gastroenterol. 2000;6:293–4.
Li Z, Xia X, Zhang S, Zhang A, Bo W, Zhou R. Up-regulation of Toll-like receptor 4 was suppressed by emodin and baicalin in the setting of acute pancreatitis. Biomed Pharmacother. 2009;63:120–8.
Wang G, Sun B, Gao Y, Meng QH, Jiang HC. The effect of emodin assisted early enteral nutrition on severe acute pancreatitis and secondary hepatic injury. Mediators Inflamm. 2007;2007:29638.
Zhang H, Yu C, Jia JY, Leung SW, Siow YL, Man RY, et al. Contents of four active components in different commercial crude drugs and preparations of danshen (Salvia miltiorrhiza). Acta Pharmacol Sin. 2002;23:1163–8.
Wu L, Qiao H, Li Y, Li L. Protective roles of puerarin and Danshensu on acute ischemic myocardial injury in rats. Phytomedicine. 2007;14:652–8.
Wang XJ, Wang ZB, Xu JX. Effect of salvianic acid A on lipid peroxidation and membrane permeability in mitochondria. J Ethnopharmacol. 2005;97:441–5.
Muhs BE, Patel S, Yee H, Marcus S, Shamamian P. Inhibition of matrix metalloproteinases reduces local and distant organ injury following experimental acute pancreatitis. J Surg Res. 2003;109:110–7.
Kusske AM, Rongione AJ, Ashley SW, McFadden DW, Reber HA. Interleukin-10 prevents death in lethal necrotizing pancreatitis in mice. Surgery. 1996;120:284–9.
Kumar A, Dhawan S, Aggarwal BB. Emodin (3-methyl-1,6,8-trihydroxyanthraquinone) inhibits TNF-induced NF-kappaB activation, IkappaB degradation, and expression of cell surface adhesion proteins in human vascular endothelial cells. Oncogene. 1998;17:913–8.
Li HL, Chen HL, Li H, Zhang KL, Chen XY, Wang XW, et al. Regulatory effects of emodin on NF-kappaB activation and inflammatory cytokine expression in RAW 264.7 macrophages. Int J Mol Med. 2005;16:41–7.
Kuo YC, Meng HC, Tsai WJ. Regulation of cell proliferation, inflammatory cytokine production and calcium mobilization in primary human T lymphocytes by emodin from Polygonum hypoleucum Ohwi. Inflamm Res. 2001;50:73–82.
Ding M, Ye TX, Zhao GR, Yuan YJ, Guo ZX. Aqueous extract of Salvia miltiorrhiza attenuates increased endothelial permeability induced by tumor necrosis factor-α. Int Immunopharmacol. 2005;5:1641–51.
Ding M, Yuan YJ. Study on the mechanisms of an extract of Salvia miltiorrhiza on the regulation of permeability of endothelial cells exposed to tumor necrosis factor-alpha. J Pharm Pharmacol. 2007;59:1027–33.
Zhou L, Zuo Z, Chow MS. Danshen: an overview of its chemistry, pharmacology, pharmacokinetics, and clinical use. J Clin Pharmacol. 2005;45:1345–59.
Cao CM, Xia Q, Zhang X, Xu WH, Jiang HD, Chen JZ. Salvia miltiorrhiza attenuates the changes in contraction and intracellular calcium induced by anoxia and reoxygenation in rat cardiomyocytes. Life Sci. 2003;72:2451–63.
Jiang H, Ha T, Wei D. A study on the mechanism of the biological roles of danshensu on fibroblast. Zhonghua Shao Shang Za Zhi. 2001;17:36–8.
Zhang QB, Gu KR. Dihydroxyacetophenone and dihydroxyphenyllactic acid increased blood flow in rat liver microcirculation. Zhong Xi Yi Jie He Za Zhi. 1987;7:608–9.
Zhu L, Shao YD, Dai HJ, Dong JC, Xue F. Effects of sodium beta-3,4-dihydroxyphenyl lactate and beta-phenyl lactic acid on prostacycline and thromboxane A2 contents in the plasma of rabbits after coronary artery occlusion. Zhongguo Yao Li Xue Bao. 1986;7:533–6.
Li CZ. Experimental study on the anticoagulative action of Danshensu. Zhong Xi Yi Jie He Za Zhi. 1983;3:297–9.
Dong ZT, Jiang WD. Effect of danshensu on isolated swine coronary artery perfusion preparation (author’s transl). Yao Xue Xue Bao. 1982;17:226–8.
Zhao BL, Jiang W, Zhao Y, Hou JW, Xin WJ. Scavenging effects of Salvia miltiorrhiza on free radicals and its protection for myocardial mitochondrial membranes from ischemia-reperfusion injury. Biochem Mol Biol Int. 1996;38:1171–82.
Wang CY, Ma FL, Liu JT, Tian JW, Fu FH. Protective effect of salvianic acid A on acute liver injury induced by carbon tetrachloride in rats. Biol Pharm Bull. 2007;30:44–7.
Smith SM, Eng RH, Buccini F. Use of d-lactic acid measurements in the diagnosis of bacterial infections. J Infect Dis. 1986;154:658–64.
Bhatia M, Wong FL, Cao Y, Lau HY, Huang J, Puneet P, et al. Pathophysiology of acute pancreatitis. Pancreatology. 2005;5:132–44.
Paszkowski AS, Rau B, Mayer JM, Moller P, Beger HG. Therapeutic application of caspase 1/interleukin-1beta-converting enzyme inhibitor decreases the death rate in severe acute experimental pancreatitis. Ann Surg. 2002;235:68–76.
Oruc N, Ozutemiz AO, Yukselen V, Nart D, Celik HA, Yuce G, et al. Infliximab: a new therapeutic agent in acute pancreatitis? Pancreas. 2004;28:el–8.
Chen CJ, Kono H, Golenbock D, Reed G, Akira S, Rock KL. Identification of a key pathway required for the sterile inflammatory response triggered by dying cells. Nat Med. 2007;13:851–6.
Rau B, Paszkowski A, Lillich S, Baumgart K, Moller P, Beger HG. Differential effects of caspase-1/interleukin-1beta-converting enzyme on acinar cell necrosis and apoptosis in severe acute experimental pancreatitis. Lab Invest. 2001;81:1001–13.
Gross V, Leser HG, Heinisch A, Scholmerich J. Inflammatory mediators and cytokines—new aspects of the pathophysiology and assessment of severity of acute pancreatitis? Hepatogastroenterology. 1993;40:522–30.
Bhatia M, Brady M, Shokuhi S, Christmas S, Neoptolemos JP, Slavin J. Inflammatory mediators in acute pancreatitis. J Pathol. 2000;190:117–25.
Dunn JA, Li C, Ha T, Kao RL, Browder W. Therapeutic modification of nuclear factor Kappa B binding activity and tumor necrosis factor-alpha gene expression during acute biliary pancreatitis. Am Surg. 1997;63:1036–43.
Zhang XP, Li ZJ, Liu DR. Progress in research into the mechanism of Radix salviae miltiorrhizae in treatment of acute pancreatitis. Hepatobiliary Pancreat Dis Int. 2006;5:501–4.
Hughes CB, el-Din AB, Kotb M, Gaber LW, Gaber AO. Calcium channel blockade inhibits release of TNF alpha and improves survival in a rat model of acute pancreatitis. Pancreas. 1996;13:22–8.
Acknowledgments
The authors would like to thank Ms.LIU Mei-na for her help with statistical analysis. This work was supported in part by grants from New Century Support Foundation for Elitist of Chinese Ministry of Education (NCET-07-0248), Scientific Foundation for Prominent Youth of Heilongjiang Province, China (JC200717), Scientific and Technical Foundation from Department of Education of Heilongjiang Province, China (11521127) and Scientific Foundation of the First Affiliated Hospital of Harbin Medical University, China (2007006).
Author information
Authors and Affiliations
Corresponding author
Additional information
Responsible Editor: A. Bauhofer
Rights and permissions
About this article
Cite this article
Wang, G., Sun, B., Zhu, H. et al. Protective effects of emodin combined with danshensu on experimental severe acute pancreatitis. Inflamm. Res. 59, 479–488 (2010). https://doi.org/10.1007/s00011-009-0152-1
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00011-009-0152-1