Gossypium herbaceam L. Extracts Ameliorate Disequilibrium of IL- 1RA/IL-1β Ratio to Attenuate Inflammatory Process induced by Amyloidβ in Rats

A chronic inflammatory response possibly mediated by Amyloid beta (A beta) is believed to be a major factor in the pathology of Alzheimer's disease (AD). Studies suggest that the mediators of the inflammatory response, which might contribute to brain damage, involve cytokines, such as IL-1 beta. IL-1 beta could play an important part in the development of pathologic conditions. There is also an endogenous interleukin-1 receptor antagonist (IL-1RA) in IL-1 family, which could prevent the actions of IL-1 beta by competing for receptor binding without inducing any signal transduction. Therefore, the balance of IL-1 beta vs IL-1RA is a critical parameter in determining not only whether excessive host inflammation will occur, but also the degree of subsequent host cell damage and associated toxicity. In our previous study, it has been determined that the anti-inflammatory action of Gossypium herbaceam L. extracts (GHE) was involved in its neuroprotection. However, the effects of GHE on IL-1 beta and IL-1RA have not been clearly defined in the experimental rat model of AD induced by A beta. Therefore, the current study is performed to evaluate whether GHE could affect the disequilibrium of IL-1RA/IL-1 beta ratio in the hippocampus of rats after A beta treatment. Subsequently, we further identify that GHE could efficaciously promote Akt and GSK3 beta phosphorylation, and thereby contribute to IL-1 beta release decrease as well as a concurrent increase in the level of IL-1RA through NF-kappa B and MAPK pathways. As a consequence, GHE is potentially beneficial to maintain the endogenous IL-1RA/IL-1 beta balance in the hippocampus of rats and it might be a potential agent to ameliorate inflammatory process in AD.