Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, Shaanxi, China; Department of Traditional Chinese Medicine, Shaanxi Provincial People's Hospital, Xi'an 710068, Shaanxi, China.
Department of Neonatal, Shaanxi Provincial People's Hospital, Xi'an 710068, Shaanxi, China.
Int Immunopharmacol. 2018 Feb;55:120-127. doi: 10.1016/j.intimp.2017.11.037. Epub 2017 Dec 22.
Atherosclerosis is a chronic inflammatory disease arising from an imbalance in lipid levels and the accumulation of cholesterol-laden macrophages in the artery wall. Crocin is an active ingredient of Crocus sativus L. This study established a rat coronary atherosclerosis model induced by vitamin D3 (VD3), to explore the effect of Crocin on lipid metabolism, macrophage polarization and the activity of inflammatory proteins. The results revealed that Crocin decreased blood lipid levels by decreasing the levels of endothelin (ET), total cholesterol (TC), triglyceridelow (TG) and low-density lipoprotein cholesterol (LDL-c), elevating the level of high-density lipoprotein cholesterin (HDL-c). Crocin also inhibited lipogenesis by suppressing the expression of lipogenesis-related proteins and elevating lipid catabolism-related proteins. Moreover, Crocin effectively alleviated inflammation by suppressing the expression of pro-inflammatory cytokines and increasing levels of anti-inflammatory cytokines. We further found that Crocin promoted macrophage polarization to the M2 phenotype by reducing M1 markers (CD40 and CD11c) and elevating M2 markers (CD68 and CD206). Finally, Crocin strongly inhibited the expression of NF-κB p65 and its translocation into the nucleus. Crocin partially counteracted nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 expression and the nuclei accumulation caused by NF-κB p65 overexpression. Taken together, our research indicated that Crocin inhibited lipogenesis and alleviated the inflammation in a VD3-induced rat coronary atherosclerosis model by promoting M2 macrophage polarization and maybe by inhibiting NF-κB p65 nuclear translocation. This study implicates Crocin as a potential therapeutic strategy for coronary atherosclerosis.
动脉粥样硬化是一种慢性炎症性疾病，源于脂质水平失衡和胆固醇负荷巨噬细胞在动脉壁中的积累。西红花苷是藏红花 Crocus sativus L. 的一种活性成分。本研究建立了维生素 D3 (VD3) 诱导的大鼠冠状动脉粥样硬化模型，以探讨西红花苷对脂代谢、巨噬细胞极化和炎症蛋白活性的影响。结果表明，西红花苷通过降低内皮素 (ET)、总胆固醇 (TC)、甘油三酯 (TG) 和低密度脂蛋白胆固醇 (LDL-c) 水平，升高高密度脂蛋白胆固醇 (HDL-c) 水平来降低血脂水平。西红花苷还通过抑制脂生成相关蛋白的表达和升高脂质分解代谢相关蛋白的水平来抑制脂生成。此外，西红花苷通过抑制促炎细胞因子的表达和增加抗炎细胞因子的水平来有效缓解炎症。我们进一步发现，西红花苷通过降低 M1 标志物 (CD40 和 CD11c) 和升高 M2 标志物 (CD68 和 CD206) 来有效促进巨噬细胞向 M2 表型极化。最后，西红花苷强烈抑制 NF-κB p65 的表达及其向核内易位。西红花苷部分抵消了 NF-κB p65 过表达引起的 NF-κB p65 表达和核内积累。综上所述，我们的研究表明，西红花苷通过促进 M2 巨噬细胞极化和抑制 NF-κB p65 核易位，抑制脂生成和缓解 VD3 诱导的大鼠冠状动脉粥样硬化模型中的炎症，提示西红花苷可能是治疗冠状动脉粥样硬化的潜在策略。
