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. 2010 Mar 8;471(3):134-8.
doi: 10.1016/j.neulet.2010.01.026. Epub 2010 Jan 22.

Fish oil enhances anti-amyloidogenic properties of green tea EGCG in Tg2576 mice

Brian Giunta  1 , Houyan Hou, Yuyan Zhu, Jon Salemi, Amanda Ruscin, R Douglas Shytle, Jun Tan
Affiliations

Fish oil enhances anti-amyloidogenic properties of green tea EGCG in Tg2576 mice

Brian Giunta et al. Neurosci Lett. .

Abstract

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.

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Figures

Fig. 1
Fig. 1. Reduction of cerebral Aβ/β-amyloid pathology in PSAPP mice that received chow containing EGCG or EGCG + Fish Oil for eight weeks
(A) Coronal sections from frozen mouse brain were stained with rabbit polyclonal anti-human Aβ antibody (4G8). (B) Percentages of Aβ antibody-immunoreactive Aβ plaque (mean ± SD) were calculated by quantitative image analysis. (C) Aβ1-40, 42 brain levels were measured by ELISA. T- test for independent samples revealed significant differences (**P < 0.001) between groups for each brain region examined in EGCG alone (low dose) and EGCG at the same dose in conjunction with fish oil.
Fig. 2
Fig. 2. Fish oil may enhance oral bioavailability of green tea-EGCG in Tg2576 mice
Analysis of free EGCG in mice treated with EGCG alone (including the high and low doses), and also from Tg2576 mice treated with EGCG (low dose) and fish oil. Percent differences of blood and brain EGCG were quantified via HPLC. T- test for independent samples revealed a significant difference in plasma levels of free EGCG in the mice co-treated with fish oil compared to mice treated with EGCG alone (**P < 0.001). Most importantly, nonsignificance between blood and brain tissues was observed for this elevated plasma level of free EGCG in these mice (P > 0.05); suggesting plasma free EGCG could freely penetrate the blood-brain-barrier (BBB).
Fig. 3
Fig. 3. Fish oil may enhance green tea-EGCG promoted non-amyloidogenic APP processing
(A). sAPP-α levels were measured in cell-cultured media by ELISA. Data are presented as mean ± SEM of sAPP-α (ng/mg total plasma protein). (B) Western blot (WB) analysis analysis consistently shows increased sAPP-α levels in cultured media from co-treated condition versus EGCG at 5 μM or fish oil alone. (C)As quantified in comparison to total protein (normalization), densitometry analysis shows significantly increased WB band density as indicated in Figure 3C (P < 0.001). Data presented as mean ± SD of WB band density. Results are representative of three independent experiments. Note: EGCG ++, 20 μM; EGCG +, 5 μM; fish oil dose, 10 γg/mL in a salt form (Sigma).
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References

    1. Almkvist O, Basun H, Wagner SL, Rowe BA, Wahlund LO, Lannfelt L. Cerebrospinal fluid levels of alpha-secretase-cleaved soluble amyloid precursor protein mirror cognition in a Swedish family with Alzheimer disease and a gene mutation. Arch Neurol. 1997;54(5):641–644. - PubMed
    1. Bailey AR, Giunta BN, Obregon D, Nikolic WV, Tian J, Sanberg CD, Sutton DT, Tan J. Peripheral biomarkers in Autism: secreted amyloid precursor protein- alpha as a probable key player in early diagnosis. Int J Clin Exp Med. 2008;1(4):338–344. - PMC - PubMed
    1. Barberger-Gateau P, Raffaitin C, Letenneur L, Berr C, Tzourio C, Dartigues JF, Alperovitch A. Dietary patterns and risk of dementia: the Three-City cohort study. Neurology. 2007;69(20):1921–1930. - PubMed
    1. Colussi G, Catena C, Baroselli S, Nadalini E, Lapenna R, Chiuch A, Sechi LA. Omega-3 fatty acids: from biochemistry to their clinical use in the prevention of cardiovascular disease. Recent Patents Cardiovasc Drug Discov. 2007;2(1):13–21. - PubMed
    1. Funamoto S, Morishima-Kawashima M, Tanimura Y, Hirotani N, Saido TC, Ihara Y. Truncated carboxyl-terminal fragments of beta-amyloid precursor protein are processed to amyloid beta-proteins 40 and 42. Biochemistry. 2004;43(42):13532–13540. - PubMed

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