Anti-Amyloidogenic Effect of Thiacremonone through Anti-Inflamation In Vitro and In Vivo Models

Neuroinflammation is implicated for amyloidogenesis. Sulfur compounds extracted from garlic have been shown to have anti-inflammatory properties. Previously, we have investigated that thiacremonone, a sulfur compound isolated from garlic has anti-inflammatory effects. To investigate thiacremonone's potential effect on anti-neuroinflammation and anti-amyloidogenesis, 4 week old ICR mice were given different doses of thiacremonone (1, 3, and 10 mg/kg) in drinking water for 1 month and received intraperitoneal injection of lipopolysaccharide (LPS) (250 mu g/kg/day) for the last 7 days of treatment. Our data show thiacremonone decreased LPS-induced memory impairment, glial activation, pro-inflammatory mediators' expression, and amyloidogenesis. In an in vitro study, we obtained similar results, with thiacremonone (1, 2, and 5 mu g/ml) effectively decreased LPS (1 mu g/ml)-induced glial activation and inflammatory mediators generation which are implicated in amyloidogenesis. Our data also demonstrated that thiacremonone inhibited LPS-induced amyloidogenesis in cultured astrocytes and microglial BV-2 cells. NF-kappa B, a critical transcriptional factor regulating not only inflammation but also amyloid-beta generation, was inhibited by thiacremonone via blocking of phosphorylation of I kappa B alpha in mice brain as well as cultured astrocytes and microglial BV-2 cells. These results indicate that the anti-inflammatory compound, thiacremonone, inhibited neuroinflammation and amyloidogenesis through inhibition of NF-kappa B activity, and thus could be applied for intervention of inflammation-related neurodegenerative disease including Alzheimer's disease.