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Published on: September 26, 2018
Curcumin Protects against Atherosclerosis in Apolipoprotein E-Knockout Mice by Inhibiting Toll-like Receptor 4
Shanshan Zhang1, Jun Zou2, Peiyang Li1
1Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Preventive Medicine, School of Public Health, Sun Yat-sen University , Guangzhou 510080, China.
Abstract:
Toll-like receptor 4 (TLR4) has been reported to play a critical role in the pathogenesis of atherosclerosis, the current study aimed to investigate whether curcumin suppresses atherosclerosis development in ApoE-knockout (ApoE-/-) mice by inhibiting TLR4 expression. ApoE-/- mice were fed a high-fat diet supplemented with or without curcumin (0.1% w/w) for 16 weeks. Curcumin supplementation significantly reduced TLR4 expression and macrophage infiltration in atherosclerotic plaques. Curcumin also reduced aortic interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) expression, nuclear factor-κB (NF-κB) activity, and plasma IL-1β, TNF-α, soluble VCAM-1 and ICAM-1 levels. In addition, aortic sinus sections revealed that curcumin treatment reduced the extent of atherosclerotic lesions and inhibited atherosclerosis development. In vitro, curcumin inhibited NF-κB activation in macrophages and reduced TLR4 expression induced by lipopolysaccharide. Our results indicate that curcumin protects against atherosclerosis at least partially by inhibiting TLR4 expression and its related inflammatory reaction.
Insights
Curcumin, a compound found in turmeric, effectively suppresses atherosclerosis development in mice by inhibiting Toll-like receptor 4 (TLR4) expression and reducing inflammation. This study highlights curcumin
Area of Science:
- Cardiovascular Research
- Immunology
- Pharmacology
Background:
- Atherosclerosis is a chronic inflammatory disease.
- Toll-like receptor 4 (TLR4) plays a key role in atherosclerosis pathogenesis.
- Inhibiting TLR4 may offer a therapeutic strategy.
Purpose of the Study:
- To investigate curcumin's effect on atherosclerosis development in ApoE-knockout mice.
- To determine if curcumin suppresses atherosclerosis by inhibiting TLR4 expression.
- To explore curcumin's impact on inflammatory markers and pathways.
Main Methods:
- ApoE-knockout mice were fed a high-fat diet with or without curcumin for 16 weeks.
- TLR4 expression, macrophage infiltration, and inflammatory markers (IL-1β, TNF-α, VCAM-1, ICAM-1) were assessed.
- Nuclear factor-κB (NF-κB) activity and atherosclerotic lesion extent were measured.
- In vitro experiments evaluated curcumin's effect on TLR4-induced NF-κB activation in macrophages.
Main Results:
- Curcumin supplementation significantly reduced TLR4 expression and macrophage infiltration in atherosclerotic plaques.
- Curcumin decreased levels of inflammatory cytokines (IL-1β, TNF-α) and adhesion molecules (VCAM-1, ICAM-1) in aorta and plasma.
- Curcumin treatment inhibited NF-κB activity and reduced the extent of atherosclerotic lesions.
- In vitro, curcumin inhibited lipopolysaccharide-induced NF-κB activation and TLR4 expression in macrophages.
Conclusions:
- Curcumin protects against atherosclerosis development in ApoE-knockout mice.
- Curcumin exerts its protective effects, at least partially, by inhibiting TLR4 expression.
- Curcumin suppresses atherosclerosis by reducing TLR4-mediated inflammatory responses.
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