Protection against beta-amyloid peptide toxicity in vivo with long-term administration of ferulic acid.
1. beta-Amyloid peptide (A beta), a 39 -- 43 amino acid peptide, is believed to induce oxidative stress and inflammation in the brain, which are postulated to play important roles in the pathogenesis of Alzheimer's disease. Ferulic acid is an antioxidant and anti-inflammatory agent derived from plants; therefore, the potential protective activity of ferulic acid against A beta toxicity in vivo was examined. 2. Mice were allowed free access to drinking water (control) or water containing ferulic acid (0.006%). After 4 weeks, A beta 1-42 (410 pmol) was administered via intracerebroventricular injection. 3. Injection of control mice with A beta 1-42 impaired performance on the passive avoidance test (35% decrease in step-through latency), the Y-maze test (19% decrease in alternation behaviour), and the water maze test (32% decrease in percentage time in platform-quadrant). In contrast, mice treated with ferulic acid prior to A beta 1-42 administration were protected from these changes (9% decrease in step-through latency; no decrease in alternation behaviour; 14% decrease in percentage time in platform-quadrant). A beta 1-42 induced 31% decrease in acetylcholine level in the cortex, which was tended to be ameliorated by ferulic acid. 4. In addition, A beta 1-42 increased immunoreactivities of the astrocyte marker glial fibrillary acidic protein (GFAP) and interleukin-1 beta (IL-1 beta) in the hippocampus, effects also suppressed by pretreatment with ferulic acid. 5. Administration of ferulic acid per se unexpectedly induced a transient and slight increase in GFAP and IL-1 beta immunoreactivity in the hippocampus on day 14, which returned to basal levels on day 28. A slight (8%) decrease in alternation behaviour was observed on day 14. 6. These results demonstrate that long-term administration of ferulic acid induces resistance to A beta 1-42 toxicity in the brain, and suggest that ferulic acid may be a useful chemopreventive agent against Alzheimer's disease.
Yan
J J
JJ
Department of Pharmacology, College of Medicine, Institute of Natural Medicine, Hallym University, Chunchon, 200-702, S. Korea.
Cho
J Y
JY
Kim
H S
HS
Kim
K L
KL
Jung
J S
JS
Huh
S O
SO
Suh
H W
HW
Kim
Y H
YH
Song
D K
DK
D000109:Acetylcholine / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001362:Avoidance Learning / Q000187:drug effects; D003373:Coumaric Acids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004326:Drinking; D016166:Free Radical Scavengers / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis / Q000276:immunology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000032:analysis / Q000276:immunology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D018384:Oxidative Stress / Q000187:drug effects; D013997:Time Factors
D016229:Amyloid beta-Peptides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003373:Coumaric Acids; D016166:Free Radical Scavengers; D005904:Glial Fibrillary Acidic Protein; D007375:Interleukin-1; C004999:ferulic acid; D000109:Acetylcholine