关键词: Baoyuan decoction CD36 Peroxidized fatty acid

Mesh : Animals Atherosclerosis / drug therapy CD36 Antigens / metabolism Drugs, Chinese Herbal / pharmacology Humans Male Mice Foam Cells / drug effects metabolism Lipoproteins, LDL / metabolism Diet, High-Fat Fatty Acids Mice, Inbred C57BL THP-1 Cells Plaque, Atherosclerotic / drug therapy MAP Kinase Signaling System / drug effects Apolipoproteins E

来  源:   DOI:10.1016/j.phymed.2024.155668

Abstract:
BACKGROUND: Baoyuan decoction (BYD) has been widely utilized as a traditional prescription for the treatment of various conditions such as coronary heart disease, aplastic anemia, and chronic renal failure. However, its potential efficacy in improving atherosclerosis has not yet been investigated.
OBJECTIVE: Our research aimed to assess the potential of BYD as an inhibitor of atherosclerosis and uncover the underlying mechanism by which it acts on foam cell formation.
METHODS: High-fat diet-induced ApoE-/- mice were employed to explore the effect of BYD on atherosclerosis. The differential metabolites in feces were identified and analyzed by LC-Qtrap-MS. In addition, we utilized pharmacological inhibition of BYD on foam cell formation induced by oxLDL in THP-1 cells to elucidate the underlying mechanisms specifically in macrophages.
RESULTS: The atherosclerotic plaque burden in the aortic sinus of ApoE-/- mice was notably reduced with BYD treatment, despite no significant alterations in plasma lipids. Metabolomic analysis revealed that BYD suppressed the increased levels of peroxidized fatty acids, specifically 9/13-hydroxyoctadecadienoic acid (9/13-HODE), in the feces of mice. As a prominent peroxidized fatty acid found in oxLDL, we confirmed that 9/13-HODE induced the overexpression of CD36 in THP-1 macrophages by upregulating PPARγ. In subsequent experiments, the decreased levels of CD36 triggered by oxLDL were observed after BYD treatment. This decrease occurred through the regulation of the Src/MMK4/JNK pathway, resulting in the suppression of lipid deposition in THP-1 macrophages.
CONCLUSIONS: These results illustrate that BYD exhibits potential anti-atherosclerotic effects by inhibiting CD36 expression to prevent foam cell formation.
摘要:
背景:保元汤(BYD)已被广泛用作治疗冠心病等各种疾病的传统处方,再生障碍性贫血,慢性肾功能衰竭.然而,其改善动脉粥样硬化的潜在功效尚未得到研究.
目的:我们的研究旨在评估比亚迪作为动脉粥样硬化抑制剂的潜力,并揭示其作用于泡沫细胞形成的潜在机制。
方法:采用高脂饮食诱导的ApoE-/-小鼠观察BYD对动脉粥样硬化的影响。通过LC-Qtrap-MS鉴定和分析粪便中的差异代谢物。此外,我们利用BYD对THP-1细胞中oxLDL诱导的泡沫细胞形成的药理学抑制作用来阐明巨噬细胞中特定的潜在机制.
结果:BYD治疗可显著降低ApoE-/-小鼠主动脉窦内的动脉粥样硬化斑块负荷,尽管血浆脂质没有明显变化。代谢组学分析显示,比亚迪抑制了过氧化脂肪酸水平的增加,特别是9/13-羟基十八碳二烯酸(9/13-HODE),在老鼠的粪便中。作为在oxLDL中发现的一种显著的过氧化脂肪酸,我们证实9/13-HODE通过上调PPARγ诱导THP-1巨噬细胞中CD36的过表达。在随后的实验中,BYD治疗后观察到oxLDL触发的CD36水平降低。这种减少是通过调节Src/MMK4/JNK途径而发生的,从而抑制THP-1巨噬细胞中的脂质沉积。
结论:这些结果表明,BYD通过抑制CD36表达以防止泡沫细胞形成而表现出潜在的抗动脉粥样硬化作用。
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