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.