Inhibition of helicobacter pylori CagA-induced pathogenesis by methylantcinate B from Antrodia camphorata
Journal
Evidence-based Complementary and Alternative Medicine
Journal Volume
2013
Date Issued
2013
Author(s)
Abstract
The bacterial pathogen Helicobacter pylori (Hp) is the leading risk factor for the development of gastric cancer. Hp virulence factor, cytotoxin-associated gene A (CagA) interacted with cholesterol-enriched microdomains and leads to induction of inflammation in gastric epithelial cells (AGS). In this study, we identified a triterpenoid methylantcinate B (MAB) from the medicinal mushroom Antrodia camphoratawhich inhibited the translocation and phosphorylation of CagA and caused a reduction in hummingbird phenotype in HP-infected AGS cells. Additionally, MAB suppressed the Hp-induced inflammatory response by attenuation of NF-B activation, translocation of p65 NF-B, and phosphorylation of IB-α, indicating that MAB modulates CagA-mediated signaling pathway. Additionally, MAB also suppressed the IL-8 luciferase activity and its secretion in HP-infected AGS cells. On the other hand, molecular structure simulations revealed that MAB interacts with CagA similarly to that of cholesterol. Moreover, binding of cholesterol to the immobilized CagA was inhibited by increased levels of MAB. Our results demonstrate that MAB is the first natural triterpenoid which competes with cholesterol bound to CagA leading to attenuation of Hp-induced pathogenesis of epithelial cells. Thus, this study indicates that MAB may have a scope to develop as a therapeutic candidate against Hp CagA-induced inflammation. ? 2013 Chun-Jung Lin et al.
SDGs
Other Subjects
antibiotic agent; antiinflammatory agent; CagA protein; I kappa B alpha; immunoglobulin enhancer binding protein; interleukin 8; methylantcinate b; triterpenoid; unclassified drug; antiinflammatory activity; Antrodia camphorata; article; bacterial strain; competitive inhibition; controlled study; enzyme activity; enzyme linked immunosorbent assay; epithelium cell; Helicobacter pylori; human; human cell; molecular interaction; pathogenesis; phenotype; priority journal; protein blood level; protein localization; protein phosphorylation; protein protein interaction; protein secretion; signal transduction; stomach epithelium
Type
journal article