During our investigation of the neuroprotective activity of Platycodi radix we found that an aqueous extract of this folk medicine exhibited significant protection against glutamate-induced toxicity in primary cultured rat cortical cells. In order to clarify the neuroprotective mechanism(s) of this observed effect, activity-guided isolation was performed to seek and identify active fractions and components. By such fractionation, four known triterpene saponin compounds -platycodins A, C and D and deapioplatycodin D -were isolated from the n-butanol fraction. Among these four compounds, platycodin A exhibited significant neuroprotective activities against glutamate-induced toxicity, exhibiting cell viability of about 50 %, at concentrations ranging from 0.1 µM to 10 µM. Therefore, the neuroprotective effect of Platycodi radix might be due to the inhibition of glutamate-induced toxicity by the saponin compounds it contains.

The accumulation of β -amyloid (Aβ) aggregates is a characteristic of Alzheimer's disease (AD). Furthermore, these aggregates have neurotoxic effects on cells, and thus, molecules that inhibit Aβ aggregate formation could be valuable therapeutics for AD. It is well known that aggregation of Aβ depends on its hydrophobicity, and thus, in order to increase the hydrophilicity of Aβ, we considered using citrate, an anionic surfactant with three carboxylic acid groups. W e hypothesized that citrate could reduce hydrophobicity and increase hydrophilicity of Aβ1-40 molecules via hydrophilic/electrostatic interactions. W e found that citrate significantly inhibited Aβ1-40 aggregation and significantly protected SH-SY5Y cell line against Aβ1-40 aggregates-induced neurotoxicity. In details, we examined the effects of citrate on Aβ1-40 aggregation and on Aβ1-40 aggregates-induced cytotoxicity, cell viability, and apoptosis. Th-T assays showed that citrate significantly inhibited Aβ1-40 aggregation in a concentrationdependent manner (Th-T intensity: from 91.3% in 0.01 mM citrate to 82.1% in 1.0 mM citrate vs. 100.0% in Aβ1-40 alone). In cytotoxicity and viability assays, citrate reduced the toxicity of Aβ1-40 in a concentration-dependent manner, in which the cytotoxicity decreased from 107.5 to 102.3% as compared with Aβ1-40 aggregates alone treated cells (127.3%) and the cell viability increased from 84.6 to 93.8% as compared with the Aβ1-40 aggregates alone treated cells (65.3% ). Furthermore, Hoechst 33342 staining showed that citrate (1.0 mM) suppressed Aβ1-40 aggregates-induced apoptosis in the cells. This study suggests that citrate can inhibit Aβ1-40 aggregation and protect neurons from the apoptotic effects of Aβ1-40 aggregates. Accordingly, our findings suggest that citrate administration should be viewed as a novel neuroprotective strategy for AD.