Fish oil enhances anti-amyloidogenic properties of green tea EGCG in Tg2576 mice.
Extracellular plaques of beta-amyloid (Abeta) peptides are implicated in Alzheimer's Disease (AD) pathogenesis. Abeta formation is precluded by alpha-secretase, which cleaves within the Abeta domain of APP generating soluble APP-alpha (sAPP-alpha). Thus, alpha-secretase upregulation may be a target AD therapy. We previously showed green tea derived EGCG increased sAPP-alpha in AD mouse models. However, the comparable effective dose of EGCG in humans may exceed clinical convenience and/or safety. Epidemiological studies suggested fish oil consumption is associated with reduced dementia risk. Here we investigated whether oral co-treatment with fish oil (8mg/kg/day) and EGCG (62.5mg/kg/day or 12.5mg/kg/day) would reduce AD-like pathology in Tg2576 mice. In vitro co-treatment of N2a cells with fish oil and EGCG enhanced sAPP-alpha production compared to either compound alone (P<0.001). Fish oil enhanced bioavailability of EGCG versus EGCG treatment alone (P<0.001). Fish oil and EGCG had a synergetic effect on inhibition of cerebral Abeta deposits (P<0.001) suggesting moderate supplementation with EGCG and fish oil having significant therapeutic potential for the treatment of AD.
Giunta
Brian
B
Department of Psychiatry and Behavioral Medicine, Neuroimmunology Laboratory, University of South Florida, College of Medicine, Tampa, FL 33613, USA. bgiunta@health.usf.edu <bgiunta@health.usf.edu>
Hou
Houyan
H
Zhu
Yuyan
Y
Salemi
Jon
J
Ruscin
Amanda
A
Shytle
R Douglas
RD
Tan
Jun
J
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000682:Amyloid / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001682:Biological Availability; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002392:Catechin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004357:Drug Synergism; D005260:Female; D005395:Fish Oils / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008822:Mice, Transgenic; D013662:Tea
D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D005395:Fish Oils; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate