A novel synthetic compound shows antioxidant and anti-inflammatory activity and alleviates cognitive deficits in rats for the treatment of Alzheimer's disease.

Abstract

Alzheimer's disease (AD) is a progressive dementia, and β-amyloid (Aβ) accumulation is widely regarded as the primary pathogenesis of AD. A new synthetic compound, 8-hydroxyquinoline-resveratrol derivative (E)-5-(4-hydroxystyryl)quinolin-8-ol (10c) was evaluated as a possible anti-AD agent. (I) The total amount of ROS in SH-SY5Y cells was detected by dichlorofluorescein diacetate (DCFH-DA), and the antioxidant activity and neuroprotective effect of 10c in SH-SY5Y cells were evaluated; (II) Griess reagent was used to test the activity of Compound 10c against NO production in LPS-induced BV-2 microglial cells; (III) An automatic digital stereotaxic instrument was used to inject Aβ25-35 into the brain to establish an AD animal model to evaluate the protective effect of compound 10c on Aβ25-35-induced learning and memory dysfunction in rats. 10c exhibited far more potent antioxidant activity for both exogenous and endogenous reactive oxygen species (ROS) than trolox, resveratrol, and CQ (ROS production: 10c with 26.23% at 1.5 µM; resveratrol with 82.17% at 2.5 µM; CQ with 78.52% at 10 µM). 10c also shows good neuroprotective effects as an endogenous antioxidant in neuroblastoma cells. Moreover, Compound 10c also demonstrated effective inhibition of nitric oxide (NO) production (IC50 =3.10 µM) and IL-1β production in BV-2 microglial cells which were treated with lipopolysaccharide (LPS). In the water maze test, the numbers of rats who crossed the former platform were increased significantly in both the 10c group (5.7±1.6) and positive control group (CQ, 5.1±1.7). Meanwhile, both 10c (43.8±5.5 s) and CQ (44.1±6.6 s) treatment could significantly prolong the time rats spent in the target quadrant compared to the vehicle-treated model group. These results demonstrated that 10c could alleviate the learning and memory dysfunction of rats induced by Aβ25-35 to a certain extent. Altogether, compound 10c is a promising compound for the treatment of AD.