Ren et al[17] reported that water soluble fraction of SSM could remove the all type of bacteria selleck chemical Z-VAD-FMK such as gram-positive, gram-negative bacteria and fungi. Because one of the main causes of AP would be bacterial infection[29,30], the removal ability of SSM would be helpful to protect AP. Thus, the anti-microbial ability of SSM might contribute to inhibition of pancreatic inflammation. Amylase and lipase levels are used alone, or in combination, to diagnose patients with AP[31]. An increased level of serum amylase, at least 3 times over the normal limit, indicates AP. Amylase activity rises quickly during the early phase after the onset of symptoms and returns to normal quickly[31]. Serum amylase activities could reflect the exocrine pancreatic insufficiency, thus resulting in mal-digestion[32].

In comparison with serum amylase activity, serum lipase activity remains increased (up to 16-28 fold) for longer, thereby giving greater opportunity in patients with a delayed presentation. Pancreatic lipase activities are less likely to be affected by other environmental factors[33]. Thus, the serum amylase and lipase activities play a key role in determining the severity of AP. In this experiment, cerulein stimulation resulted in significant elevation in serum amylase and lipase levels. This increase was inhibited by SSM pre-treatment, suggesting that SSM is effective against the induction of AP (Figure (Figure22). The activation of inflammatory cells that release cytokines such as TNF-�� and IL-1�� is an important cascade in the pathogenesis of AP[34-36].

TNF-�� and IL-1�� are derived predominantly from activated macrophages and act via specific cell membrane-bound receptors. Levels of both these pro-inflammatory mediators are elevated on initiation of and during AP[37,38]. Intrapancreatic TNF-�� and IL-1�� can be detected 1 h after induction of AP, and the levels of these cytokines increase rapidly over the next 6 h[37,38]. Recently, many studies have reported that both TNF-�� and IL-1�� play an important role in AP[7,39]. In our experimental model of pancreatitis, the serum levels of TNF-�� and IL-1�� were elevated during AP. However, when mice were pre-treated with SSM water extract, this elevation of TNF-�� and IL-1�� was inhibited (Figures (Figures33 and and66). In this study, we examined the role of HMGB-1 as a late inflammatory mediator in AP.

Batimastat Generally, HMGB-1, a DNA-binding intranuclear protein, is known to be a late activator in the inflammatory cascade[10]. HMGB-1 has the capacity to induce cytokines and activate inflammatory cells when applied extracellularly[10]. This implicates that HMGB-1 is a pro-inflammatory mediator. Recent investigations reported that serum HMGB-1 levels increase in patients with sepsis/endotoxemia[40], hemorrhagic shock[41], acute lung injury[42], rheumatoid arthritis[43], and disseminated intravascular coagulation[44].