Anti-inflammatory effects of [6]-shogaol: Potential roles of HDAC inhibition and HSP70 induction

Ginger extracts have been reported to have anti-inflammatory, anti-oxidant, and anti-cancer effects. [6]-shogaol is one of the most bioactive components of ginger rhizomes. This study assessed the [6]-shogaol's ability to protect cultured primary rat astrocytes against lipopolysaccharide (LPS)-induced inflammation. [6]-shogaol was shown to suppress the release of pro-inflammatory cytokines and decreased the level of inducible nitric oxide syntheses (iNOS), cyclooxygenase-2 (COX-2), and phospho-NF-kB in LPS-treated astrocytes. Furthermore, [6]-shogaol treatment markedly up-regulated histone H3 acetylation and suppressed histone deacetylase (HDAC)1 expression. In addition, [6]-shogaol treatment also increased the expression of heat-shock protein (HSP)70. The neuroprotective, neurotrphic, and anti-inflammatory properties of [6]-shogaol may be translated to improvements in neurological performance. [6]-Shogaol's ability to inhibit HDAC was comparable to that of commonly used HDAC inhibitors Trichostatin A and MS275. Taken together, our results suggest that [6]-shogaol can significantly attenuate a variety of neuroinflammatory responses by inducing HSP70, that is associated with HDAC inhibition in cortical astrocytes.