Compound AD110 Acts as Therapeutic Management for Alzheimer's Disease and Stroke in Mouse and Rat Models.

ABSTRACT

Anti-inflammatory therapy may be an effective therapeutic intervention for neurological diseases, such as Alzheimer's disease (AD) and stroke. As an important anti-inflammatory cytokine, interleukin-10 (IL-10) inhibits proinflammatory responses of both innate and adaptive immune cells. We tested the hypothesis that drug-induced promotion of IL-10 expression is effective in improving cognitive abilities and neurologic outcomes of AD and stroke. An orally small molecule AD110 was synthesized and subjected to in vitro and in vivo analyses. We found that AD110 enhanced IL-10 release in lipopolysaccharide (LPS)-activated BV2 microglial cells. Y-Maze and Morris water maze tests showed improved cognitive abilities in AD mice treated with AD110. Moreover, AD110 attenuated cerebral ischemic injury in a transient middle cerebral artery occlusion (tMCAO) rat model. This study not only provides a promising lead compound with IL-10-promoting activity, but also supports the hypothesis that promoting IL-10 expression is a potential therapeutic strategy for AD and stroke.