• The Korean Journal of Physiology and Pharmacology
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• v.2 no.5
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• pp.629-635
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• 1998

It has been suggested that oxygen free radicals are involved in the initiation process of acute pancreatitis, although its pathogenesis is not clear. This study evaluates the roles of oxygen radicals and the effects of small molecular antioxidants (rebamipide, N-acetyl-cysteine, allopurinol, ${\beta}-carotene)$ on the development of cerulein-induced acute pancreatitis. Acute edematous pancreatitis was induced by the intravenous infusion of cerulein at supramaximal dose of 10 ${\mu}g/kg/hour$ for 3.5 hours. The effects of antioxidants, rebamipide (100 mg/kg, i.p.), N-acetyl-cysteine (200 mg/kg, i.v.), allopurinol (20 mg/kg/hour), ${\beta}-carotene$ (50 mg/kg, i.p.), were examined. Cerulein administration resulted in a significant increase in serum amylase activity and pancreatic malondialdehyde (MDA), but not glutathione peroxidase (GSHpx). The glutathione (GSH) content in pancreatic tissue decreased dramatically. Pretreatment of N-acetyl-cysteine significantly decreased the cerulein-induced hyperamylasemia and maintained GSH content in pancreas, but MDA was slightly decreased. In addition, N-acetyl-cysteine ameliorated histological damage. Allopurinol and ${\beta}-carotene$ attenuated cerulein-induced hyperamylasemia, but histologically there was no difference from control. These results indicate that oxygen free radicals play an important role in the initiation of experimental acute pancreatitis. N-acetyl-cysteine is an effective antioxidant that ameliorates the cerulein-induced acute pancreatitis, and the possible therapeutic application of antioxidants against acute pancreatitis needs a further evaluation.

• Journal of Life Science
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• v.23 no.10
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• pp.1280-1287
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• 2013

The current study investigated the effects of [6]-gingerol, a ginger phytochemical, on the expression of autophagy-related genes and the activation of antioxidative enzymes in the pancreas of mice with cerulein-induced acute pancreatitis. The following were studied: pancreatic edema, ${\alpha}$-amylase activity in serum, expression of autophagy genes, activities of antioxidative defense enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the production of lipid peroxidation (LPO). The results revealed that cerulein-induced edema in the pancreas and ${\alpha}$-amylase activity in the cerulein group significantly increased compared with that of the control. However, that of the [6]-gingerol pretreated group was significantly decreased compared with that of the cerulein-alone injected group (positive control). There was no significant difference compared with that of control. The expression of autophagy-related proteins, including Beclin-1 and cleaved microtubule-associated protein 1 light chain 3, were significantly increased in the positive control but significantly decreased in the [6]-gingerol-pretreated group. Furthermore, the activities of SOD and GSH-Px in the positive control were decreased compared with those of the control. However, those of the [6]-gingerol pretreated group were significantly increased compared with those of the cerulein-alone group. The mRNA levels and antioxidant enzyme activities were similar. The production of LPO in the cerulein with and without [6]-gingerol groups was increased by 133.1% and 26.3%, respectively, compared with that of the control, whereas that of the [6]-gingerol-pretreated group was significantly decreased by 48.5% compared with that of the positive control. Therefore, [6]-gingerol may be a strong candidate in reducing autophagy and LPO production and in enhancing antioxidative enzyme activities to help prevent acute and chronic pancreatitis.

• The Korea Journal of Herbology
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• v.27 no.5
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• pp.9-14
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• 2012

Objective : We investigated the effect of Poncirus trifoliata and Citrus aurantium extract in mice with cerulein-induced acute pancreatitis (AP) model. Methods : AP was induced via intraperitoneal injection of cerulein (50 ${\mu}g/kg$) given every hour for 6h. Poncirus trifoliata (PT: 200 or 400 mg/kg) and Citrus aurantium (CA: 200 or 400 mg/kg) extract were injected 1 h before in mice with cerulein-induced AP. Mice were sacrificed at 6 h after last injection of cerulein. Blood samples were taken to determine serum amylase and lipase levels. The pancreas and lungs were rapidly removed for morphological examination, myeloperoxidase assay. Results : PT pre-treatment significantly protected the pancreas and lung damages and reduced the MPO activity and serum amylase in cerulein-induced AP. However, CA pre-treatment did not significantly protected the pancreas and lung inflammation in cerulein-induced AP. Conclusion : These results suggest that PT but not CA could protect the cerulein-induced AP. Conclusion : These results suggest that PT but not CA could protect the cerulein-induced AP.

• Journal of Physiology & Pathology in Korean Medicine
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• v.34 no.6
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• pp.334-340
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• 2020

Nypa fruticans Wurmb. (NF) has been used as a folk remedy to treat inflammatory diseases in Asia. In this study, we aimed to investigate the protective effect of NF water extract on cerulein-induced acute pancreatitis (AP). To measure the protective effects of NF on AP, AP was induced via intraperitoneal injection of cerulein (50 ㎍/kg) hourly for 6 h in mice. NF water extract (100, 250, or 500 mg/kg) or saline was administrated to intraperitoneal injection 1 h before the first injection of cerulein. The mice were sacrificed at 6 h after the final injection of the cerulein. Pancreas, and blood sample were taken for further analysis. Administration of NF water extract inhibited the pancreatic injury, the elevation of pancreatic weight/ body weight ratio, and the elevation of serum digestive enzymes such as amylase and lipase during cerulein-induced AP in mice. Also, pancreas MPO activity, which represents neutrophil infiltration, was inhibited by administration of NF water extract. Taken together, administration of NF water extract reduces the severity of cerulein-induced AP, which suggests a clinical basis that NF could be a potential agent to prevent AP.

• Journal of Convergence Korean Medicine
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• v.5 no.2
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• pp.5-10
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• 2023

Objectives: Terminalia chebula Retzins (TC) has been used as a traditional remedy to treat gastrointestinal infectious and inflammatory diseases. However, the protective effect of TC on acute pancreatitis (AP) has not been studied. In this study, we tried to investigate the protective effect of TC water extract on cerulein-induced AP. Methods: To measure the protective effect of TC on AP, mice were injected with cerulein (50 ㎍/kg) hourly for 6 times. TC water extract (200 or 400 mg/kg) or saline was administered orally 1 h before the first injection of cerulein. The mice were sacrificed at 6 h after the last injection of cerulein. Pancreas tissues were taken for further analysis. Results: The administration of TC water extract showed an inhibitory effect on the increase of pancreas weight/body weight ratio and mitigated pancreatic damage in mice. Also, mRNA level of pro-inflammatory cytokines was inhibited by administration of TC water extract. Conclusion: Taken together, we found that administration of TC water extract ameliorates the severity of cerulein-induced AP, which suggests the potential to be an effective treatment on AP.

• The Korea Journal of Herbology
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• v.29 no.3
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• pp.11-17
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• 2014

Objective : Portulaca oleracea (PO) has been used as an important traditional medicine for inflammatory and bacterial diseases in East Asia. However, the protective effects of PO on acute pancreatitis (AP) is not well-known. Therefore, this study was performed to identify the anti-inflammatory and prophylactic effects of PO on cerulein-induced AP. Methods : AP was induced in mice via intraperitoneal injection of supramaximal concentrations of the stable cholecystokinin analogue cerulein ($50{\mu}g/kg$) given every hour for 6 times. Water extracts of PO (100, 300, or 500 mg/kg) was administrated intra-peritoneally 1 h prior to the first injection of cerulein. The mice were killed at 6 h after the final cerulein injection. Pancreas and lung were rapidly removed for morphologic and histochemical examination, myeloperoxidase (MPO) assay. Blood samples were taken to determine serum amylase and lipase activities. Results : Administration of PO significantly inhibited pancreatic weight/body weight ratio, pancreas and lung histological injury. And MPO activity which indicates neutrophil infiltration was inhibited by PO extracts on cerulein-induced pancreatitis. In addition, PO administration inhibited digestive enzymes such as serum amylase and lipase activity on cerulein-induced pancreatitis. Conclusion : Our results could suggest that pre-treatment of PO reduces the severity of cerulein-induced AP, thereby, PO could be used as a protective agent against AP. Also, this study could give a clinical basis that PO could be a drug or agent to prevent AP.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.6
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• pp.409-416
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• 2009

Acute pancreatitis is a multifactorial disease associated with the premature activation of digestive enzymes. The genes expressed in pancreatic acinar cells determine the severity of the disease. The present study determined the differentially expressed genes in pancreatic acinar cells treated with cerulein as an in vitro model of acute pancreatitis. Pancreatic acinar AR42J cells were stimulated with $10^{-8}$ M cerulein for 4 h, and genes with altered expression were identified using a cDNA microarray for 4,000 rat genes and validated by real-time PCR. These genes showed a 2.5-fold or higher increase with cerulein: lithostatin, guanylate cyclase, myosin light chain kinase 2, cathepsin C, progestin-induced protein, and pancreatic trypsin 2. Stathin 1 and ribosomal protein S13 showed a 2.5-fold or higher decreases in expression. Real-time PCR analysis showed time-dependent alterations of these genes. Using commercially available antibodies specific for guanylate cyclase, myosin light chain kinase 2, and cathepsin C, a time-dependent increase in these proteins were observed by Western blotting. Thus, disturbances in proliferation, differentiation, cytoskeleton arrangement, enzyme activity, and secretion may be underlying mechanisms of acute pancreatitis.

• The Journal of Internal Korean Medicine
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• v.36 no.2
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• pp.105-121
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• 2015

Objectives: This study investigated the effects of Gagam-daewhang mangcho-tang (GDM) and its components on cerulein-induced acute pancreatitis (AP) in mice Methods: The AP mouse model was induced by intra-peritoneal injection of cerulein (50 μg/kg) at hourly intervals for 6 times. The experimental drug was administrated intraperitoneally 1 hour prior to the first injection of cerulein. Mice were sacrificed at 6 hours after the last injection of cerulein. Blood samples were taken to determine serum amylase level. The pancreas and lungs were rapidly removed for histochemical examination and myeloperoxidase (MPO) assays. Results: Administration of modified GDM significantly reduced the ratio of pancreas/body weight, level of serum amylase, neutrophil infiltration, and histological damage of the pancreas and lung. In a test of the components of GDM, the Salvia miltiorrhiza (SM) group showed a significant suppression of the severity of AP. In an experiment testing the concentration of SM, the 150 mg/kg SM group showed significant attenuation of the severity of AP. Conclusions: Modified GDM and a SM water extract could attenuate AP and AP-associated lung injury via suppression of digestive enzyme secretion and MPO activity.

• The Korea Journal of Herbology
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• v.33 no.2
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• pp.45-52
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• 2018

Objectives : Smilacis Glabrae Rhizoma (SGR) has been used in traditional medicine for treating diseases related to inflammation and cancer. However, the protective effect of SGR has not been reported in the study of acute pancreatitis (AP). Therefore, this study was performed to evaluate the protective effects of SGR water extract on cerulein-induced AP. Methods : AP was induced by intraperitoneal injection of supramaximal concentrations of stable cholecystokinin analogue cerulein ($50{\mu}g/kg$) 6 times at intervals of one hour in mice. SGR water extract (0.01, 0.05, or 0.1 g/kg) was administrated intraperitoneally 1 h prior to the first injection of cerulein. The mice were sacrificed at 6 h after the final injection of cerulein. Pancreas and lung were rapidly removed for histochemical examination and myeloperoxidase (MPO) assay. In addition, polymerase chain reaction (PCR) was performed to examine mRNA levels of proinflammatory cytokines such as interleukin(IL)-6, $IL-1{\beta}$ and Tumor necrosis $factor(TNF)-{\alpha}$. Results : Administration of SGR water extract significantly inhibited pancreatic weight to body weight ratio. In addition, SGR treatment inhibited the histological damages and increase of MPO activity in both pancreas and lung during AP. Also, mRNA levels of IL-6 but not $IL-1{\beta}$and $TNF-{\alpha}$ were inhibited by SGR water extract against AP. Conclusion : Our results revealed that pre-treatment of SGR water extract reduces the severity of cerulein-induced AP. Therefore, this study suggest that SGR could be used as a drug or agent to prevent AP.

• The Korea Journal of Herbology
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• v.29 no.6
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• pp.15-20
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• 2014

Objectives : Commiphora myrrha (CM) has been used in traditional medicine for treating disease such as obesity, hyperlipidemia, atherosclerosis, diabetes and osteoarthritis. However, the protective effects of CM on acute pancreatitis (AP) has not been reported. Thus, the aim of this study was to evaluate the protective effects of CM water extract on cerulein-induced AP. Methods : AP was induced in mice via intraperitoneal injection of supramaximal concentrations of the stable cholecystokinin analogue cerulein ($50{\mu}g/kg$) every hour for 6 times. Water extract of CM (0.1, 0.2, or 0.5 g/kg) was administrated intraperitoneally 1 h prior to the first injection of cerulein. The mice were killed at 6 h after the final cerulein injection. Pancreas was rapidly removed for morphologic and histochemical examination, myeloperoxidase (MPO) assay. Blood samples were taken to determine serum amylase and lipase activities. Results : Administration of CM significantly inhibited pancreatic weight/body weight ratio, pancreas histological injury. And CM administration inhibited the serum digestive enzyme elevation such as amylase and lipase on cerulein-induced pancreatitis. In addition, Pancreas MPO activity which indicates neutrophil infiltration was inhibited by CM extract on cerulein-induced pancreatitis. Conclusions : In conclusion, our results could suggest that pre-treatment of CM reduces the severity of cerulein-induced AP. Therefore, CM could be used as a protective agent against AP. Also, this study could give a clinical basis that CM could be a drug or agent to prevent AP.