Borneol alleviates oxidative stress via upregulation of Nrf2 and Bcl-2 in SH-SY5Y cells.

Abstract

CONTEXT:

The β-amyloid (Aβ) peptide aggregation with accompanying oxidative stress plays the major role in the pathogenesis of Alzheimer's disease (AD). Some natural compounds, including borneol, shed promising light on AD treatment.

OBJECTIVE:

The present study was designed to investigate the antioxidative, antiapoptotic effects, and neuroprotection of borneol in human neuroblastoma cells (SH-SY5Y).

MATERIALS AND METHODS:

Oxidative stress was induced by administering 50 µM Aβ into SH-SY5Y cells. Neuroprotective effect of commercially available borneol was examined by determining cell viability with the MTT assay. Intracellular reactive oxygen species (ROS) generation was measured using a fluorometer with further examination of heme oxygenase-1 (HO-1) and nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) expression. Apoptosis was examined by measuring the ratio of B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax).

RESULTS:

Our data indicated that Aβ-induced cell cytotoxicity was inhibited by 100 µM of (-) and (+) borneol treatment. Treatment of borneol significantly decreased ROS generation (P < 0.01). The expression of HO-1 and nuclear translocation of Nrf2 were increased by Aβ treatment. This nuclear translocation of Nrf2 was further increased by administration of borneol. Compared with the Aβ treated group, the (+) borneol treated group significantly increased Bcl-2 expression with decreased expression of Bax.

DISCUSSION AND CONCLUSION:

Borneol protected SH-SY5Y cells against Aβ-induced toxicity, exerted an antioxidative effect and suppressed apoptosis. It increases our knowledge about neuroprotective mechanism of borneol, and it is hopeful to be a candidate compound for developing therapeutic drug for the prevention and treatment of AD and other Aβ-related neurodegenerative diseases.

• Authors: Jinyoung Hur, Sok Cheon Pak, Byung-Soo Koo, Songhee Jeon
• Journal: Pharmaceutical biology (Pharm Biol) Vol. 51 Issue 1 Pg. 30-5 (Jan 2013) ISSN: 1744-5116 [Electronic] England
• PMID: 23134284 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Antioxidants
• Camphanes
• NF-E2-Related Factor 2
• NFE2L2 protein, human
• Neuroprotective Agents
• Peptide Fragments
• Proto-Oncogene Proteins c-bcl-2
• Reactive Oxygen Species
• amyloid beta-protein (1-42)
• bcl-2-Associated X Protein
• isoborneol

Topics

• Amyloid beta-Peptides (antagonists & inhibitors, toxicity)
• Antioxidants (chemistry, pharmacology)
• Apoptosis (drug effects)
• Camphanes (chemistry, pharmacology)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Fluorometry
• Humans
• NF-E2-Related Factor 2 (genetics)
• Neuroblastoma (metabolism)
• Neuroprotective Agents (chemistry, pharmacology)
• Oxidative Stress (drug effects)
• Peptide Fragments (antagonists & inhibitors, toxicity)
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
• Reactive Oxygen Species (metabolism)
• Up-Regulation (drug effects)
• bcl-2-Associated X Protein (genetics, metabolism)