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Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice
Published on: September 26, 2018
Sinomenine protects against atherosclerosis in apolipoprotein E-knockout mice by inhibiting of inflammatory pathway
Zhao Gao1, Chao Yang2, Guangwei Zeng1
1Department of Cardiology, Xi'an International Medical Center Hospital, Xi'an, 710100, China.
Insights
Sinomenine effectively combats atherosclerosis by reducing body weight, improving lipid profiles, and mitigating inflammation and oxidative stress in ApoE-/- mice. This natural compound shows promise in early-stage atherosclerosis intervention.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Immunology
Background:
- Atherosclerosis is a chronic inflammatory disease driving cardiocerebrovascular disorders.
- Plaque formation involves cholesterol, lipids, calcium, and cellular debris in artery walls.
- Apolipoprotein E-deficient (ApoE-/-) mice are a standard model for atherosclerosis research.
Purpose of the Study:
- To investigate the anti-atherosclerotic potential of sinomenine in ApoE-/- mice.
- To evaluate sinomenine's effects on lipid metabolism, oxidative stress, and inflammation.
Main Methods:
- Atherosclerosis was induced in ApoE-/- mice using a high-fat diet.
- Mice were treated with varying doses of sinomenine (5, 10, 15 mg/kg) or simvastatin for 12 weeks.
- Evaluated parameters included body weight, food/water intake, lipid profiles, oxidative stress markers, cardiac markers, and inflammatory cytokine/mRNA levels.
Main Results:
- Sinomenine significantly suppressed body weight, food, and water intake (P < 0.001).
- It modulated lipid profiles (TC, HDL, TG, LDL, VLDL), oxidative stress markers (GPx, CAT, MDA, SOD, GSH), and cardiac parameters (CRP, ET-1, TXB2, NO, cTnI, LDH, CK-MB).
- Sinomenine reduced inflammatory cytokines (IL-1α, IL-1β, TNF-α, IL-6, IL-10) and suppressed mRNA expression of key inflammatory and adhesion molecules (IL-6, IL-17, TNF-α, MCP-1, VCAM-1, ICAM-1).
Conclusions:
- Sinomenine demonstrates significant efficacy in suppressing early-stage atherosclerosis development in ApoE-/- mice.
- The therapeutic effects are attributed to its ability to improve lipid profiles, reduce oxidative stress, and inhibit inflammatory pathways.
- Sinomenine represents a potential therapeutic agent for managing atherosclerosis.
Abstract:
Atherosclerosis, a multifaceted and persistent inflammatory condition, significantly contributes to the progression of cardiocerebrovascular disorders, such as myocardial infarctions and cerebrovascular accidents. It involves the accumulation of cholesterol, fatty deposits, calcium and cellular debris in the walls of arteries, leading to the formation of plaques. Our aim is to investigate the potential of sinomenine to counteract atherosclerosis in mice lacking Apolipoprotein E (ApoE-/-) Mice. We employed the high-fat diet-induced method to induce atherosclerosis in ApoE-/- mice, and the mice were treated with sinomenine (5, 10, and 15 mg/kg) and simvastatin (0.5 mg/kg) for 12 weeks. Body weight, water intake, and food intake were assessed. Lipid parameters, oxidative stress, inflammatory cytokines, and mRNA levels were estimated. Sinomenine treatment remarkably (P < 0.001) suppressed body weight, along with food and water intake. Sinomenine altered the levels of total cholesterol (TC), high-density lipoprotein (HDL), triglyceride (TG), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL), which were modulated in the atherosclerosis group. Sinomenine treatment also altered the levels of oxidative stress parameters such as glutathione peroxidase (GPx), catalase (CAT), malonaldehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH). In addition, it modulated cardiac parameters like C-reactive protein (CRP), endothelin-1 (ET-1), thromboxane B2 (TXB2), nitric oxide (NO), cardiac troponin I (cTnI), lactate dehydrogenase (LDH), and creatinine kinase isoenzymes (CK-MB). Inflammatory cytokines interleukin (IL)-1α, IL-1β, TNF-α, IL-6, and IL-10 were also affected. Sinomenine further suppressed the mRNA expression of IL-6, IL-17, IL-10, tumor necrosis factor-α (TNF-α), Il-1β, monocyte chemoattractant protein-1 (MCP-1), MCP-2, MCP-3, transforming Growth Factor-1β (TGF-1β), vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1). The results suggest that sinomenine remarkably suppressed the development of atherosclerosis in the early stage.
