Cyanidin-3-glucoside inhibits amyloid β_25–35-induced neuronal cell death in cultured rat hippocampal neurons

Abstract

Increasing evidence implicates changes in [Ca2+]i and oxidative stress as causative factors in amyloid beta (Aβ)-induced neuronal cell death. Cyanidin-3-glucoside (C3G), a component of anthocyanin, has been reported to protect against glutamate-induced neuronal cell death by inhibiting Ca2+ and Zn2+ signaling. The present study aimed to determine whether C3G exerts a protective effect against Aβ25–35-induced neuronal cell death in cultured rat hippocampal neurons from embryonic day 17 fetal Sprague-Dawley rats using MTT assay for cell survival, and caspase-3 assay and digital imaging methods for Ca2+, Zn2+, MMP and ROS. Treatment with Aβ25–35 (20 µM) for 48 h induced neuronal cell death in cultured rat pure hippocampal neurons. Treatment with C3G for 48 h significantly increased cell survival. Pretreatment with C3G for 30 min significantly inhibited Aβ25–35-induced [Zn2+]i increases as well as [Ca2+]i increases in the cultured rat hippocampal neurons. C3G also significantly inhibited Aβ25–35-induced mitochondrial depolarization. C3G also blocked the Aβ25–35-induced formation of ROS. In addition, C3G significantly inhibited the Aβ25–35-induced activation of caspase-3. These results suggest that cyanidin-3-glucoside protects against amyloid β-induced neuronal cell death by reducing multiple apoptotic signals.

Comparative Transcriptome Analysis of the Expression of Antioxidant and Immunity Genes in the Spleen of a Cyanidin 3-O-Glucoside-Treated Alzheimer’s Mouse Model

“…C3G is protective against glutamate-induced neuronal cell death [ 20 ] and ischemia-induced neuronal cell death [ 21 , 22 ]. It can prevent ethanol neurotoxicity [ 23 ] and can protect against amyloid β(Aβ)-induced cytotoxicity [ 23 , 24 , 25 ]. It can also promote the inhibition of Aβ (Aβ40, Aβ1-42) fibrillization and protect neuronal cells from Aβ1-42, Aβ40, and Aβ25-35 induced cytotoxicity [ 6 , 24 , 25 , 26 , 27 ].…”

“…It can prevent ethanol neurotoxicity [ 23 ] and can protect against amyloid β(Aβ)-induced cytotoxicity [ 23 , 24 , 25 ]. It can also promote the inhibition of Aβ (Aβ40, Aβ1-42) fibrillization and protect neuronal cells from Aβ1-42, Aβ40, and Aβ25-35 induced cytotoxicity [ 6 , 24 , 25 , 26 , 27 ]. In rats, C3G can prevent the cognitive impairment induced by Aβ [ 28 ].…”

TPEN attenuates amyloid-β25–35-induced neuronal damage with changes in the electrophysiological properties of voltage-gated sodium and potassium channels

“…Herein, exposure of primary hippocampal neurons to 20 μM Aβ 25–35 for 24 h significantly decreased neuronal viability and increased the intracellular Zn 2+ concentration, whereas TPEN, a membrane-permeable Zn 2+ -specific chelator, attenuated Aβ 25–35 -induced neuronal death and reversed Aβ 25–35 -induced intracellular Zn 2+ concentration increase. Coincidentally, Yang et al recently reported that treatment with Aβ 25–35 increased intracellular Zn 2+ , then might cause mitochondrial depolarization, formation of ROS, the activation of caspase-3, and neuron damage in cultured rat hippocampal neurons, also suggesting synergy neurotoxic effects of intracellular Zn 2+ and amyloid beta [ 53 ]. Taken together, intracellular Zn 2+ dysregulation mediated the neurotoxicity of Aβ 25–35 , and it may be an effective strategy for preventing Aβ-induced neuronal damage by capturing Zn 2+ released from intracellular Zn-Aβ complexes.…”

Synthesis and Cytotoxic Activities of Resveratrol and Valproic Acid Ester Derivatives with Anti-Bladder-Cancer Effects

“…Cytotoxicity of compound 2 was evaluated using an MTT assay. 32 First, compound 2 was dissolved in DMSO. Then, it was dissolved in the free medium immediately before being used for cell treatment and was followed by 70% sonication and ltration of the material through a 0.45-µM lter (Millipore, Billerica, MA, USA).…”