4’,5,7-三羥基黃酮對幽門螺旋桿菌感染胃腺癌細胞發炎之抑制
摘要
Helicobacter pylori has been classified as a group I carcinogen by WHO in 1994. Cag A+ H. pylori infection results in serious gastric epithelial cell inflammation, atrophic gastritis, and then progresses to gastric cancer. 4’,5,7- trihydroxyflavone, one of flavonoids, abounds in fruits and vegetables, especially in basil, cilantro, and parsley. As reported, 4’,5,7-trihydroxyflavone exhibited anti-inflammatory, anti-cancer, and anti-oxidative activities. In this study, we investigated in vitro effect of 4’,5,7- trihydroxyflavone on the H. pylori-induced inflammation, in which the inflammatory factor expressions including COX-2、IL-6、IL-8、ICAM-1 and ROS and other factors such as MUC-2 were examined. The relevant mechanisms of 4’,5,7- trihydroxyflavone are proposed. In the results, viabilities for MKN45 cells and H. pylori were 88 and 53%, respectively, at 20 μg/mL treatment. H. pylori stimulation initiated the NF-κB pathway, in which the IκBα expression significantly increased at 20 μg/mL of treatment dose (218% of that of the control). 4’,5,7- trihydroxyflavone significantly decreased the inflammatory factor (i.e. COX-2、IL-6、IL-8、ICAM-1 and ROS) expressions, for which, IL-8 and ICAM-1 levels were 77 and 69 %, respectively, of that of the controls at 10 μg/mL treatment as well as 40 and 72% of that of the controls, respectively, for the hydrogen peroxide and superoxide anion production at 2.5 μg/mL treatment. Additionally, 10 μg/mL of 4’,5,7- trihydroxyflavone significantly increased both MUC-2 mRNA and protein expressions (133 and 184% of that of the controls). In the H. pylori-infected MKN45 gastric adenocarcinoma cell model system, 4’,5,7- trihydroxyflavone showed a critical role in (1) the inhibition of NF-κB activation, thus down-regulating the downstream inflammatory factors such as COX-2, ICAM-1, IL-8 and IL-6; (2) scavenging the high amounts of hydrogen peroxide and superoxide anions induced by neutrophil and H. pylori lipopolysaccharide; (3) the promotion of m