International journal of molecular medicine

Luteolin protects mice from severe acute pancreatitis by exerting HO-1-mediated anti-inflammatory and antioxidant effects.

PMID 27878246


Resedaxa0odorataxa0L. 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 Resedaxa0odorataxa0L., which is also widely found in many natural herbs and vege-tables, has been shown to induce heme oxygenase-1xa0(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 pancreatitisxa0(SAP), and to explore the underlying mechanisms. Cerulein and lipopolysaccharide were used to induce SAP in male Institute of Cancer Researchxa0(ICR) mice in the SAP group. The SAPxa0group was divided into 4xa0subgroups, as follows: the vehicle, luteolin, zinc protoporphyrinxa0(ZnPP) only, and luteolinxa0(Lut)xa0+xa0ZnPPxa0(luteolin plus zinc protoporphyrin treatment) groups. The wet/dryxa0weight 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-κBxa0(NF-κB) and myeloperoxidase activities, and malondialdehyde, tumor necrosis factorxa0αxa0(TNFα), interleukinxa0(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 Lutxa0group exhibited a significant increase in HO-1xa0expression in the pancreas and enhanced serum HO-1 andxa0IL-10xa0levels compared with the vehicle group. The suppression of HO-1 activity in the ZnPPxa0group significantly abolished the protective effects of luteolin. NF-κB expression in the pancreatic tissues from the mice in the Lutxa0+xa0ZnPPxa0group 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.