Abstract
Corallodiscus flabellata B. L. Burtt (CF) is a Chinese folk herb with reported potential for the treatment of Alzheimer's disease (AD). 3,4-Dihydroxyphenylethanol-8-O-[4-O-trans-caffeoyl-β-D-apiofuranosyl-(1→3)-β-D-glucopyranosyl (1→6)][1]-β-D-glucopyranoside (SDC-1-8) and hydroxytyrosol (HT) are two polyphenolic compounds isolated from CF. The aim of this study was to investigate the protective effects of SDC-1-8 and HT on an Aβ25-35-induced AD model and to study the underlying mechanism. The AD mouse model was established using a brain injection of amyloid β-protein 25-35 (Aβ25-35, 200 μM), followed by continuous administration of SDC-1-8 and HT for 4 weeks, and found that they improved cognitive dysfunction; ameliorated neuronal damage and apoptosis; decreased oxidative stress, and mitochondrial fission protein levels; and increased mitochondrial fusion protein levels in AD mice. Moreover, SDC-1-8 and HT inhibited mitochondrial membrane depolarization, reduced intracellular stored Ca2+ levels, enhanced mitochondrial respiration, increased mitochondrial fusion, and decreased mitochondrial division in Aβ25-35-induced PC12 cells even in the presence of mdivi-1. Furthermore, molecular docking simulations showed that SDC-1-8 and HT interacted with dynamin-related protein 1 with higher affinity than mitofusin 1. Thus, it is summarized that SDC-1-8 and HT may have neuroprotective effects by balancing the abnormalities of mitochondrial fission and fusion, and SDC-1-8 and HT are the components providing the therapeutic basis of CF.