Chonnam Med J.  2014 Aug;50(2):45-51. 10.4068/cmj.2014.50.2.45.

Effects of Flavonoid Compounds on beta-amyloid-peptide-induced Neuronal Death in Cultured Mouse Cortical Neurons

• Choi SM
• Kim BC
• Cho YH
• Choi KH
• Chang J
• Park MS
• Kim MK
• Cho KH
• Kim JK

• KMID: 2172158
• DOI: http://doi.org/10.4068/cmj.2014.50.2.45

Abstract

Excessive accumulation of beta-amyloid peptide (Abeta) is one of the major mechanisms responsible for neuronal death in Alzheimer's disease. Flavonoids, primarily antioxidants, are a group of polyphenolic compounds synthesized in plant cells. The present study aimed to identify flavonoid compounds that could inhibit Abeta-induced neuronal death by examining the effects of various flavonoids on the neurotoxicity of Abeta fragment 25-35 (Abeta25-35) in mouse cortical cultures. Abeta25-35 induced concentration- and exposure-time-dependent neuronal death. Neuronal death induced by 20 microM Abeta25-35 was significantly inhibited by treatment with either Trolox or ascorbic acid. Among 10 flavonoid compounds tested [apigenin, baicalein, catechin, epicatechin, epigallocatechin gallate (EGCG), kaempferol, luteolin, myricetin, quercetin, and rutin], all except apigenin showed strong 1,1-diphenyl-2-pycrylhydrazyl (DPPH) scavenging activity under cell-free conditions. The flavonoid compounds except apigenin at a concentration of 30 microM also significantly inhibited neuronal death induced by 20 microM Abeta25-35 at the end of 24 hours of exposure. Epicatechin, EGCG, luteolin, and myricetin showed more potent and persistent neuroprotective action than did the other compounds. These results demonstrated that oxidative stress was involved in Abeta-induced neuronal death, and antioxidative flavonoid compounds, especially epicatechin, EGCG, luteolin, and myricetin, could inhibit neuronal death. These findings suggest that these four compounds may be developed as neuroprotective agents against Alzheimer's disease.

Keyword

beta-Amyloid peptide; Alzheimer's disease; Flavonoids

MeSH Terms

Alzheimer Disease
Animals
Antioxidants
Apigenin
Ascorbic Acid
Catechin
Flavonoids
Luteolin
Mice*
Neurons*
Neuroprotective Agents
Oxidative Stress
Plant Cells
Quercetin
Antioxidants
Apigenin
Ascorbic Acid
Catechin
Flavonoids
Luteolin
Neuroprotective Agents
Quercetin

Figure

• 

  FIG. 1 Aβ25-35-induced neuronal death in mouse cortical cultures. Phase-contrast photomicrographs from typical representative fields (200×field) of cells were taken after a 24-hour exposure to (A) sham wash or (B) 20 µM Aβ25-35 showing neurotoxic action of 20 µM Aβ25-35 in mouse cortical cultures (200×field). Treatment with Aβ25-35 induced concentration- and exposure-time-dependent neuronal death in mixed cortical cultures (C). Each point and bars are the mean±SEM from 8-20 cultured wells (C).

• 

  FIG. 2 Effect of co-treatment with Trolox (100 µM) or ascorbic acid (AA, 100 µM) on 20 µM Aβ25-35-induced neuronal death at the end of 24 and 48 hours of exposure. Each bar is the mean±SEM from 8-16 cultured wells. *Significantly different from 24-hour-treated control group (p<0.05). #Significantly different from 48-hour-treated control group (p<0.05).

• 

  FIG. 3 (A) Effects of epigallocatechin gallate (EGCG, 3, 10, 30 µM) on 20 µM Aβ25-35-induced neuronal death at the end of 24 or 48 hours of exposure. (B) Effects of luteolin (LTL, 3, 10, 30 µM) on 20 µM Aβ25-35-induced neuronal death at the end of 24 or 48 hours of exposure. (C) Effects of myricetin (MYR, 3, 10, 30 µM) on 20 µM Aβ25-35-induced neuronal death at the end of 24 or 48 hours of exposure. Each bar is the mean±SEM from 8-12 cultured wells. Other legends are the same as in Fig. 2.

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