SSM treatment also reduced pancreatic weight/body weight ratio, serum amylase, lipase and cytokine levels, and mRNA expression of multiple inflammatory mediators such as tumor necrosis factor-�� Erlotinib mechanism of action and interleukin-1��. In addition, treatment with SSM inhibited HMGB-1 expression in the pancreas during AP. In accordance with in vivo data, SSM inhibited the cerulein-induced acinar cell death, cytokine, and HMGB-1 release. SSM also inhibited the activation of c-Jun NH2-terminal kinase, p38 and nuclear factor (NF)-��B. CONCLUSION: These results suggest that SSM plays a protective role during the development of AP and pancreatitis associated lung injury via deactivating c-Jun NH2-terminal kinase, p38 and NF-��B.
Keywords: Scolopendra subspinipes mutilans, Cytokines, Acute pancreatitis, High-mobility group box protein-1 INTRODUCTION The annual incidence of acute pancreatitis (AP) is in the range of 300 or more patients per million[1,2]. The mortality rate for severe AP is approximately 30%, whereas that for moderate pancreatitis is about 3%. The main causes of death are circulatory shock renal, respiratory, and hepatic failure. Thus, many patients with AP develop multiple organ failure (MOF)[3]. Generally, AP is characterized by activation of pancreatic digestive enzyme production, widespread inflammatory cell infiltration, leukocyte activation, and release of various pro-inflammatory mediators such as tumor necrosis factor (TNF)-�� and interleukin (IL)[4-6]. Although numerous approaches have attempted to identify the pathogenesis of AP[7-9], the detailed mechanism remains unclear.
Recent studies have shown that high-mobility group box protein-1 (HMGB-1) is a late activator in the inflammatory cascade, when released into the extracellular space[10]. Neutralization of HMGB-1 has been shown to protect against systemic inflammatory responses such as in sepsis and MOF as HMGB-1 acts as a downstream cytokine of early inflammatory factors such as TNF and ILs[11-13]. In addition, HMGB-1 has been speculated to be a target for treating AP[14]. Scolopendra subspinipes mutilans (SSM) is a venomous arthropod, which can be found throughout the world. SSM and its venom have been reported to exhibit many biochemical and physiological effects[15,16]. The water soluble fractions from SSM have antimicrobial and anti-inflammatory activity and hemolytic action of the toxins[17,18].
In addition, SSM has been prescribed for the treatment of cardiovascular diseases in South Korea, China, and other Far Eastern Asian countries for several hundred years[16]. However, the protective activities of SSM in cerulein-induced AP have not been examined to date. Our study was designed to assess the protective effect of SSM in cerulein-induced AP. Entinostat Here, we investigated the in vivo and in vitro activities of SSM using a murine model of experimental pancreatitis.