3,4,5-tri-O-caffeoylquinic acid inhibits amyloid β-mediated cellular toxicity on SH-SY5Y cells through the upregulation of PGAM1 and G3PDH

Abstract

Caffeoylquinic acid (CQA) is one of the phenylpropanoids found in a variety of natural resources and foods, such as sweet potatoes, propolis, and coffee. Previously, we reported that 3,5-di-O-caffeoylquinic acid (3,5-di-CQA) has a neuroprotective effect against amyloid-β (Aβ)-induced cell death through the overexpression of glycolytic enzyme. Additionally, 3,5-di-CQA administration induced the improvement of spatial learning and memory on senescence accelerated-prone mice (SAMP8). The aim of this study was to investigate whether 3,4,5-tri-O-caffeoylquinic acid (3,4,5-tri-CQA), isolated from propolis, shows a neuroprotective effect against Aβ-induced cell death on human neuroblastoma SH-SY5Y cells. To clarify the possible mechanism, we performed proteomics and real-time RT-PCR as well as a measurement of the intracellular adenosine triphosphate (ATP) level. These results showed that 3,4,5-tri-CQA attenuated the cytotoxicity and prevented Aβ-mediated apoptosis. Glycolytic enzymes, phosphoglycerate mutase 1 (PGAM1) and glyceraldehyde-3-phosphate dehydrogenase (G3PDH) were overexpressed in co-treated cells with both 3,4,5-tri-CQA and Aβ. The mRNA expression of PGAM1, G3PDH, and phosphoglycerate kinase 1 (PGK1), and intracellular ATP level were also increased in 3,4,5-tri-CQA treated cells. Taken together the findings in our study suggests that 3,4,5-tri-CQA shows a neuroprotective effect against Aβ-induced cell death through the upregulation of glycolytic enzyme mRNA as well as ATP production activation.

Fig. 1

Structure of 3,4,5-tri-O-caffeoylquinic acid

Fig. 2

Effect of 3,4,5-tri-CQA on the Aβ_1–42 treated SH-SY5Y cells viability. SH-SY5Y cells were treated with 3,4,5-tri-CQA or 10 μM Aβ_1–42 (Aβ) for 72 h. Each bar represents the mean ± SD (n = 10). ** p < 0.01 versus control, ## p < 0.01 versus the cells treated only Aβ

Fig. 3

Two-dimensional gel electrophoresis of SH-SY5Y cells (a), the magnified images of box regions (b). SH-SY5Y cells were treated with 20 μM 3,4,5-tri-CQA or exposed to 10 μM Aβ_1–42 for 72 h. The 2-DE gel was stained with coomassie brilliant blue. Spot value was measured by ImageMaster 2D Platinum software

Fig. 4

Effect of 3,4,5-tri-CQA on the expressions of G3PDH (a), PGAM1 (b), and PGK1 (c) mRNAs by SH-SY5Y cells. β-actin was used as a housekeeping gene. The mRNA expression of PGAM1 and PGK1 was normalized by β-actin mRNA expression. SH-SY5Y cells were treated with 10 μM 3,4,5-tri-CQA for 8 and 16 h. Each bar represents the mean ± SD (n = 4). *0.01 < p < 0.05 versus control cell, **p < 0.01 versus control cell

Fig. 5

Effect of 3,4,5-tri-CQA on the intracellular ATP production of SH-SY5Y cells. SH-SY5Y cells were treated with 1, 5, and 10 μM 3,4,5-tri-CQA for 48 h. Intracellular ATP production was increased by 3,4,5-tri-CQA treatment on SH-SY5Y cells. Each bar represents the mean ± SD (n = 10). *0.01 < p < 0.05 versus control cell, **p < 0.01 versus control cell

Fig. 6

DPPH radical scavenging activity of 3,4,5-tri-CQA. Each bar represents the mean ± SD (n = 6) of the inhibition of DPPH radical (% inhibition)