Anti-amyloidogenic effect of thiacremonone through anti-inflamation in vitro and in vivo models.
Neuroinflammation is implicated for amyloidogenesis. Sulfur compounds extracted from garlic have been shown to have anti-inflammatory properties. Previously, we have investigated that thiacremonone, a sulfur compound isolated from garlic has anti-inflammatory effects. To investigate thiacremonone's potential effect on anti-neuroinflammation and anti-amyloidogenesis, 4 week old ICR mice were given different doses of thiacremonone (1, 3, and 10 mg/kg) in drinking water for 1 month and received intraperitoneal injection of lipopolysaccharide (LPS) (250 μg/kg/day) at last 7 days of treatment. Our data show thiacremonone decreased LPS-induced memory impairment, glial activation, pro-inflammatory mediators' expression, and amyloidogenesis. In an in vitro study, we obtained similar results, with thiacremonone (1, 2, and 5 μg/ml) effectively decreased LPS (1 μg/ml)-induced glial activation and inflammatory mediators generation which are implicated in amyloidogenesis. Our data also demonstrated that thiacremonone inhibited LPS-induced amyloidogenesis in cultured astrocytes and microglial BV-2 cells. NF-κB, a critical transcriptional factor regulating not only inflammation but also amyloid-β generation, was inhibited by thiacremonone via blocking of phosphorylation of IκBα in mice brain as well as cultured astrocytes and microglial BV-2 cells. These results indicated that the anti-inflammatory compound, thiacremonone, inhibited neuroinflammation and amyloidogenesis through inhibition of NF-κB activity, and thus could be applied for intervention of inflammation-related neurodegenerative disease including Alzheimer's disease.
College of Pharmacy, Chungbuk National University, Heungduk-gu, Cheongju, Chungbuk, Republic of Korea.
Gui Hua
GH
Lin
Young-Jung
YJ
Lee
Dong-Young
DY
Choi
Sang Bae
SB
Han
Jae Kyung
JK
Jung
Bang Yeon
BY
Hwang
Dong Cheul
DC
Moon
Youngsoo
Y
Kim
Myung Koo
MK
Lee
Ki-Wan
KW
Oh
Heon Sang
HS
Jeong
Jae Yoon
JY
Leem
Hwa Kyoung
HK
Shin
Jung Hwa
JH
Lee
Jin Tae
JT
Hong
D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay; D005106:Exploratory Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000517:prevention & control; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013876:Thiophenes / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D013876:Thiophenes; C075222:amyloid beta-protein (1-42); C524083:thiacremonone; D009569:Nitric Oxide; D053829:Amyloid Precursor Protein Secretases