title: Luteolin protects mice from severe acute pancreatitis by exerting HO-1-mediated anti-inflammatory and antioxidant effects.
abstract: Reseda odorata L. has long been used in traditional Asian medicine for the treatment of diseases associated with oxidative injury and acute inflammation, such as endotoxemia, acute lung injury, acute myocardial infarction and hepatitis. Luteolin, the main component of Reseda odorata L., which is also widely found in many natural herbs and vege-tables, has been shown to induce heme oxygenase-1 (HO-1) expression to exert anti-inflammatory and antioxidant effects. In this study, we aimed to examine the effects of luteolin on mice with severe acute pancreatitis (SAP), and to explore the underlying mechanisms. Cerulein and lipopolysaccharide were used to induce SAP in male Institute of Cancer Research (ICR) mice in the SAP group. The SAP group was divided into 4 subgroups, as follows: the vehicle, luteolin, zinc protoporphyrin (ZnPP) only, and luteolin (Lut) + ZnPP (luteolin plus zinc protoporphyrin treatment) groups. The wet/dry weight ratios, hematoxylin and eosin staining and pathological scores of pancreatic tissues were assessed and compared to those of the control mice. Amylase, lipase, nuclear factor-κB (NF-κB) and myeloperoxidase activities, and malondialdehyde, tumor necrosis factor α (TNFα), interleukin (IL)-6, IL-10 and HO-1 levels, as well as the expression of HO-1 were determined in serum and/or pancreatic tissue samples. SAP was successfully induced in male mice compared to normal control mice. The wet/dry weight ratios, pathological scores, and amylase and lipase activity, as well as the levels of TNFα and IL-6 were significantly reduced in the pancreatic tissues of the mice in the Lut group compared with those of the mice in the vehicle group. The Lut group exhibited a significant increase in HO-1 expression in the pancreas and enhanced serum HO-1 and IL-10 levels compared with the vehicle group. The suppression of HO-1 activity in the ZnPP group significantly abolished the protective effects of luteolin. NF-κB expression in the pancreatic tissues from the mice in the Lut + ZnPP group was significantly increased following the suppression of HO-1 activity. On the whole, our findings demonstrate that luteolin protects mice from SAP by inducing HO-1-mediated anti-inflammatory and antioxidant activities, in association with the suppression of the activation of the NF-κB pathway.
authors.affiliation: Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xiong
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Kezhou
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Pathology and Pathophysiology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Yuan
authors.affiliation: Department of Nephrology, The Second Hospital Affiliated to Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Xing
authors.affiliation: Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Ni
authors.affiliation: Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.
authors.forename: Guoyong
authors.initials: G
authors.lastname: Hu
authors.affiliation: Department of Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201999, P.R. China.
authors.forename: Fengling
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.
authors.forename: Xingpeng
authors.initials: X
authors.lastname: Wang
mesh_terms: D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D002108:Ceruletide; D002851:Chromatography, High Pressure Liquid; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000097:blood / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides; D047311:Luteolin / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008813:Mice, Inbred ICR; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D009336:Necrosis; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D010195:Pancreatitis / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology*; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011524:Protoporphyrins / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D020011:Protective Agents; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D002108:Ceruletide; D051547:Heme Oxygenase-1; D047311:Luteolin