The HO-1 inhibitor ZnPP inhibited the effect of NJ4 on cerulein-induced acinar cells (Figure (Figure8F).8F). Furthermore, the HO-1 inducer curcumin also inhibited cerulein-induced acinar cell death (Figure (Figure8F8F). Effect of NJ4-2 on in vitro acinar cell death To examine the kinase inhibitor Cabozantinib effect of NJ4-2 on HO-1 expression in isolated pancreatic acinar cells, HO-1 expression was measured. As shown in Figure 9A and B, NJ4-2 treatment increased the HO-1 expression after 1 h. The expression was increased in time dependant manner. HO-1 induction in pancreatic acinar cells occurred in a dose-dependent manner at 6 h after NJ4-2 treatment (Figure 9C and D). Figure 9 Effects of Nardostachys jatamansi-2 on heme oxygenase-1 expression in acinar cells and cerulein-induced acinar cell death.
Pancreatic acinar cells were pretreated with Nardostachys jatamansi (NJ4)-2 (10 ��g/mL), and then the cells were harvested … The cells were pretreated with NJ4-2 for 1 h and then stimulated with cerulein for 6 h. NJ4-2 significantly increased the viability of pancreatic acinar cells in a dose-dependent manner (Figure (Figure9E9E). DISCUSSION Various studies have investigated candidates that could treat AP[6,15-18]. However, specific and effective candidates to treat AP remain unknown. Our previous report showed that the total extract of NJ reduces the severity of mild acute pancreatitis[6]. In this study, we report that the biological main fraction of NJ, i.e., NJ4, has a protective effect against cerulein-induced AP. To identify the fraction responsible for the main effect of NJ, we fractionated NJ and obtained 6 fractions.
The effects of the 6 fractions on lipopolysaccharide (LPS)-induced inflammatory responses were examined in peritoneal macrophages. NJ4 significantly inhibited the LPS-induced production of inflammatory mediators such as nitric oxide (NO), IL-1, IL-6, and TNF-�� (unpublished data). Therefore, NJ4 was chosen to examine its effect on pancreatitis. Also among the 3 fractions from NJ4, NJ4-2 inhibited the inflammatory mediators significantly. Thus, we also choose NJ4-2 as NJ4��s candidate. NJ4 ameliorated the severity of AP and AP associated with lung injury and inhibited neutrophil infiltration, digestive enzymes, and cytokines. NJ4 also increased cell viability against cerulein challenge.
In the present study, we showed that the effect of NJ4 on pancreatitis was comparable with the effect of the total aqueous extract of NJ. AP remains a challenging clinical problem in which mortality is significantly increased depending on its Anacetrapib severity[19]. Despite a few clinical trials with pharmacological agents, no effective treatment exists for AP. AP is commonly caused by excessive alcohol consumption, biliary tract disease, hereditary factors, certain medications, and invasive procedures of the biliary and pancreatic ducts[20-23]. In this experiment, we used a well-established murine model.