Gastric mucosal
inflammation can develop after challenge with noxious stimuli such as alcohol. Specially, alcohol stimulates the release of inflammatory
cytokines but does not increase gastric acid secretion, leading to gastric mucosal damage. The
plant sterol guggulsterone and its novel derivative GG-52 have been reported to inhibit nuclear factor-κB (NF-κB) signaling in intestinal epithelial cells and experimental
colitis. In the present study, we investigated the anti-inflammatory effects of GG-52 on gastric epithelial cells and on
ethanol-induced gastric mucosal
inflammation in mice. GG-52 inhibited the expression of
interleukin-8 (IL-8) in gastric epithelial AGS and MKN-45 cell lines stimulated with
tumor necrosis factor (TNF)-α in a dose-dependent manner. Pretreatment with GG-52 suppressed TNF-α-induced activation of IκB
kinase (IKK) and NF-κB signaling in MKN-45 cells. In contrast, the inactive analog GG-46 did not produce significant changes in
IL-8 expression or NF-κB activation. In a model of
ethanol-induced murine
gastritis, administration of GG-52 significantly reduced the severity of
gastritis, as assessed by macroscopic and histological evaluation of gastric mucosal damage. In addition, the
ethanol-induced upregulation of
chemokine KC, a mouse homolog of
IL-8, and phosphorylated p65 NF-κB signals were significantly inhibited in murine gastric mucosa pretreated with GG-52. These results indicate that GG-52 suppresses NF-κB activation in gastric epithelial cells and ameliorates
ethanol-induced gastric mucosal lesions in mice, suggesting that GG-52 may be a potential gastroprotective agent.