Bioactive Compounds of Kimchi Inhibit Apoptosis by Attenuating Endoplasmic Reticulum Stress in the Brain of Amyloid β-Injected Mice

J Agric Food Chem. 2018 May 16;66(19):4883-4890. doi: 10.1021/acs.jafc.8b01686. Epub 2018 May 7.

Abstract

This study investigated the inhibitory effects of kimchi bioactive compounds against endoplasmic reticulum (ER) stress-induced apoptosis in amyloid beta (Aβ)-injected mice. Mice received a single intracerebroventricular injection of Aβ25-35, except for the normal group. Mice were subjected to oral administration of 10 mg of capsaicin, 50 mg of 3-(4'-hydroxyl-3',5'-dimethoxyphenyl)propionic acid (HDMPPA), 50 mg of quercetin, 50 mg of ascorbic acid, or 200 mg of kimchi methanol extract (KME) per kilogram of body weight for 2 weeks ( n = 7 per group). In the in vitro blood-brain barrier (BBB) permeability test, all bioactive compounds penetrated the BBB except ascorbic acid. The protein expression level of APP, BACE, and p-Tau elevated by Aβ injection was decreased by kimchi bioactive compounds ( P < 0.05). Quercetin, HDMPPA, and KME decreased oxidative stress, as indicated by ROS and TBARS levels ( P < 0.05). The protein expression level of ER stress markers GRP78, p-PERK, p-eIF2α, XBP1, and CHOP and the proapoptotic molecules Bax, p-JNK, and cleaved caspases-3 and -9 decreased ( P < 0.05). In contrast, the protein expression level of antiapoptotic molecules Bcl2 and cIAP increased ( P < 0.05). These results were supported by histological analysis.

Keywords: amyloid beta; apoptosis; endoplasmic reticulum stress; kimchi bioactive compound.

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / administration & dosage
  • Amyloid beta-Peptides / toxicity*
  • Animals
  • Apoptosis / drug effects*
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism
  • Brain / cytology
  • Brain / drug effects*
  • Brain / metabolism
  • Brassica / chemistry*
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Endoplasmic Reticulum Chaperone BiP
  • Endoplasmic Reticulum Stress / drug effects*
  • Fermented Foods / analysis
  • Humans
  • Infusions, Intraventricular
  • Male
  • Mice
  • Mice, Inbred ICR
  • Oxidative Stress / drug effects
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / toxicity*
  • Plant Extracts / administration & dosage*
  • Signal Transduction / drug effects
  • X-Box Binding Protein 1 / genetics
  • X-Box Binding Protein 1 / metabolism

Substances

  • Amyloid beta-Peptides
  • Endoplasmic Reticulum Chaperone BiP
  • HSPA5 protein, human
  • Hspa5 protein, mouse
  • Peptide Fragments
  • Plant Extracts
  • X-Box Binding Protein 1
  • amyloid beta-protein (25-35)
  • Caspase 3