Anti-Amyloid Aggregation Effects of Gobaishi (Galla chinensis) and Its Active Constituents

Abstract

Alzheimer's disease (AD) is a chronic neurodegenerative disorder that leads to memory loss and changes in mental and behavioral functions in elderly individuals. A major pathological feature of AD is the aggregation of amyloid-beta (Aβ) peptides, along with oxidative stress, inducing neurocellular apoptosis in the brain. Gobaishi (Galla chinensis), a traditional herbal medicine, has gained considerable attention for its constituents and potent therapeutic properties, particularly its strong inhibitory activity against Aβ fibril formation. In this study, we investigated the anti-Aβ aggregation effects of Gobaishi and its active constituents. We isolated two compounds by employing Thioflavin T (ThT) assay-guided fractionation, which were identified through various spectroscopic methods as pentagalloyl glucose (PGG) and methyl gallate (MG). Evaluation of their anti-Aβ aggregation effects revealed that PGG and MG contribute 1.5% and 0.7% of the activity of Gobaishi, respectively. In addition, PGG demonstrated significantly stronger DPPH radical scavenging activity (EC₅₀ = 1.16 µM) compared to MG (EC₅₀ = 6.44 µM). At a concentration of 30 µM, PGG significantly reduced the Aβ-induced cytotoxicity in SH-SY5Y cell lines compared to MG. Based on these findings, both Gobaishi and its active compound PGG are proposed as promising candidates for further investigation as potent anti-amyloidogenic agents in AD management.

Keywords: Gobaishi; amyloid-beta; antioxidant; methyl gallate; pentagalloyl glucose.

Figure 1

Metabolite profiling of Gobaishi using full scan mode covering negative (sid = 5) ion detection. (a) Total ion chromatogram of the EtOH fraction of Gobaishi. (b) Mass spectrum of the EtOH fraction of Gobaishi.

Figure 2

Isolation of Aβ aggregation inhibitor derived from Gobaishi.

Figure 3

Structure of (a) compound 1 (PGG) and (b) compound 2 (MG).

Figure 4

Inhibition of Aβ42 aggregation by pentagalloyl glucose (a) and methyl gallate (b). The data represent inhibitory activity as % of Aβ aggregation and are expressed as the mean ± SD; n = 3.

Figure 5

PGG inhibits Aβ aggregation as assessed by a turbidity assay. The legends are obtained from the Abs of (PGG + Aβ)−PGG. Data are presented as the mean ± SD of Abs of three independent experiments (n = 3). The asterisk (*) indicates a statistically significant difference compared to the Aβ alone group (one-tailed Student′s t-test, * p < 0.05).

Figure 6

Effect of RA (a), Gobaishi extract (b), PGG (c), and MG (d) on SH-SY5Y cells in the presence or absence of 30 μM Aβ at different concentrations. Results represent the mean  ±  SD (n  =  3). Differences between groups (Aβ vs. treatments) were evaluated for statistical significance using two-tailed Student′s t-test. * p  <  0.05, ** p  <  0.005, *** p  <  0.0005. ns stands for not significant.