Atherosclerosis (AS) is the leading cause of heart attacks, stroke, and peripheral vascular disease. Berberine (BBR), a botanical medicine, has diversified anti-atherosclerotic effects but with poor absorption. The aim of this study was to develop an effective BBR-entrapped nano-system for treating AS in high-fat diet (HFD)-fed Apoe^(−/−) mice, and also explore the possible underlying mechanisms involved. Three d-α-tocopherol polyethylene glycol (PEG) succinate (TPGS) analogues with different PEG chain lengths were synthesized to formulate BBR-entrapped micelles. HFD-fed Apoe^(−/−) mice were administered with optimized formula (BBR, 100 mg/kg/day) orally for 5 months. The artery plaque onset and related metabolic disorders were evaluated, and the underlying mechanisms were studied. Our data showed that, BT₁₅₀₀M increased BBR deposition in liver and adipose by 107.6% and 172.3%, respectively. In the Apoe^(−/−) mice, BT₁₅₀₀M ameliorated HFD-induced hyperlipidemia and lipid accumulation in liver and adipose. BT₁₅₀₀M also suppressed HFD-induced chronic inflammation as evidenced by the reduced liver and adipose levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β); and decreased plasma level of TNF-α, IL-6, IL-1β, interferon-γ (IFN-γ), monocyte chemotactic protein (MCP), and macrophage inflammatory factor (MIP). The mechanism study showed that BT₁₅₀₀M changed Ampk and Nf-κb gene expression, and interrupted a crosstalk process between adipocytes and macrophages. Further investigation proved that BT₁₅₀₀M decreased endothelial lesion and subsequent macrophage activation, cytokines release, as well as cholesteryl ester gathering in the aortic arch, resulting in ameliorated artery plaque build-up. Our results provide a practical strategy for treating AS using a BBR-entrapped nano-system.

动脉粥样硬化（AS）是心脏病，中风和周围血管疾病的主要原因。小ber碱（BBR）是一种植物药，具有多种抗动脉粥样硬化作用，但吸收性差。这项研究的目的是开发一种有效的捕获BBR的纳米系统，用于治疗高脂饮食（HFD）喂养的Apoe ^（-/-）小鼠中的AS ，并探索可能的潜在机制。合成了三种具有不同PEG链长的d - α-生育酚聚乙二醇（PEG）琥珀酸酯（TPGS）类似物，以配制包被BBR的胶束。由HFD喂养的Apoe ^（-/-）给小鼠口服优化配方食品（BBR，100 mg / kg /天），持续5个月。评价了动脉斑块发作和相关的代谢紊乱，并研究了其潜在机制。我们的数据显示，BT ₁₅₀₀ M使肝脏和脂肪中的BBR沉积分别增加107.6％和172.3％。在Apoe ^（-/-）小鼠中，BT ₁₅₀₀ M改善了HFD诱导的高脂血症以及肝脏和脂肪中的脂质蓄积。BT ₁₅₀₀ M还抑制HFD诱导的慢性炎症由缩小肝脏和白细胞介素-6（IL-6），肿瘤坏死因子的脂肪水平所证明α（TNF- α）和白细胞介素-1 β（ IL-1 β）; 血浆TNF - α，IL-6，IL- 1β，干扰素-γ（ IFN- γ），单核细胞趋化蛋白（MCP）和巨噬细胞炎性因子（MIP）水平降低。机制研究表明，BT ₁₅₀₀ M改变了Ampk和Nf-κb基因的表达，并中断了脂肪细胞和巨噬细胞之间的串扰过程。进一步的研究证明BT ₁₅₀₀ M减少了内皮病变，并减少了巨噬细胞的活化，细胞因子的释放以及胆固醇酯在主动脉弓中的聚集，从而改善了动脉斑块的形成。我们的结果提供了使用包埋BBR的纳米系统治疗AS的实用策略。