A Potential Therapeutic Effect of Saikosaponin C As a Novel Dual-target Anti-Alzheimer Agent

Alzheimer's disease (AD) is a chronic neurodegenerative disease and the risk of developing it increases with advancing age. In this study, we investigated the protective effects of saikosaponin C (SSc), one of the main bioactive components produced by the traditional Chinese herb, radix bupleuri, the root of Bupleurum falcatum, against AD in various neuronal models. Interestingly, we found that SSc has dual effects on AD by targeting amyloid beta (Aβ) and tau, two key proteins in AD. SSc significantly suppressed the release of both Aβ peptides 1-40 and 1-42 into cell culture supernatants, though it does not affect BACE1 activity and expression. SSc also inhibited abnormal tau phosphorylation at multiple AD-related residues. Moreover, SSc seems to have beneficial effects on cellular tau function; it accelerated nerve growth factor-mediated neurite outgrowth and increased the assembly of microtubules. In addition, SSc increased synaptic marker proteins such as synaptophysin and PSD-95. Considering its various biological activities, our results suggest that SSc might be a novel therapeutic tool for treating human AD and other neurodegenerative diseases. Tau and amyloid beta are two key features in Alzheimer's disease. Saikosaponin C, an active component of Bupleuri Radix, inhibits abnormal tau phosphorylation and amyloid beta production, thereby promoting synaptic integrity. Saikosaponin C also prevents amyloid beta-induced apoptosis in brain vascular endothelial cells. Therefore, Saikosaponin C may provide a new therapeutic strategy for treatment of neurodegenerative diseases, including Alzheimer's disease.