Nobiletin protects against murine l-arginine-induced acute pancreatitis in association with downregulating p38MAPK and AKT.
Acute pancreatitis (AP) is an inflammatory disease characterized by acinar cell damage, oxidative stress, and inflammation of the pancreas. Nobiletin (3',4',5,6,7,8-hexamethoxyflavone), a major polymethoxy flavone, has shown health-promoting properties in previous studies. Therefore, in this study, we investigated whether nobiletin protects against experimental AP induced with l-arginine. C57BL/6 mice were treated with 25 or 50mg/kg nobiletin by intraperitoneal injection once daily for 14 consecutive days. AP was then induced in the mice with two intraperitoneal injections of l-arginine (4g/kg). The nobiletin treatment significantly reduced the plasma amylase levels, pancreatic myeloperoxidase activity, percentage of pancreatic necrosis, plasma proinflammatory factors, the generation of reactive oxygen species, cell apoptosis, tissue damage, and the expression of phosphorylated p38MAPK (p-p38MAPK) and p-AKT. These results suggest that nobiletin is a new therapeutic method for l-arginine-induced AP in mice.
Department of Emergency, National Clinical Research Center of Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
Bing
B
Liu
Liver Research Center, National Clinical Research Center of Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
Jian
J
Huang
Department of Emergency, National Clinical Research Center of Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China. Electronic address: doc_zhang666@aliyun.com.
Bin
B
Zhang
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001120:Arginine; D016207:Cytokines / Q000097:blood; D015536:Down-Regulation / Q000187:drug effects; D047309:Flavones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D010195:Pancreatitis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D016207:Cytokines; D047309:Flavones; D020011:Protective Agents; D017382:Reactive Oxygen Species; D001120:Arginine; C008661:nobiletin; D009195:Peroxidase; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases
AKT; AP; Nobiletin; p38MAPK