Department of Rheumatology, The Third Affiliated Hospital of Anhui Medical University, Hefei, 230032, China.
Anhui Provincial Hospital, Hefei, China.
Inflammopharmacology. 2017 Dec;25(6):633-642. doi: 10.1007/s10787-017-0341-4. Epub 2017 Apr 1.
Macrophage-derived foam cells are well known for their key role in development of atherosclerosis (AS). The present study aimed to examine whether dioscin exerts anti-atherosclerotic activity and inhibits foam cell formation. A high-fat induced AS model and ox-LDL treated macrophages were established and received treatment of dioscin. Anti-atherosclerotic activity in vivo was assessed by atherosclerotic lesions size and aortic lipid contents. Macrophage formed foam cells were positively identified by oil red o staining. Moreover, the expression of LOX-1 and NF-κB in aorta tissue and macrophages was examined by western blotting assay. Our results showed that dioscin not only reduced the levels of plasma lipid, TNF-a, IL-1β and IL-6, but also inhibited atherosclerotic development in AS rats, as evidenced by decreased atherosclerotic lesions size and aortic lipid level. In vitro study revealed dioscin directly reduced foam cell formation, decreased intracellular cholesterol accumulation and lowered TNF-a, IL-1β and IL-6 secretion in ox-LDL treated macrophages. Interestingly, further work found dioscin significantly reduced expression of LOX-1 and NF-κB in the aortic tissue and ox-LDL treated macrophages. In summary, our study was the first to confirm anti-atherosclerotic activity of dioscin in vivo and vitro. Moreover, the other important finding is dioscin mediated ox-LDL/LOX-1/NF-κB regulated contributions to the attenuate macrophage ox-LDL uptake and AS.
巨噬细胞源性泡沫细胞在动脉粥样硬化(AS)的发展中起着关键作用,这是众所周知的。本研究旨在探讨薯蓣皂苷是否具有抗动脉粥样硬化活性并抑制泡沫细胞形成。建立了高脂诱导的 AS 模型和 ox-LDL 处理的巨噬细胞,并给予薯蓣皂苷治疗。通过动脉粥样硬化病变大小和主动脉脂质含量评估体内抗动脉粥样硬化活性。油红 O 染色阳性鉴定巨噬细胞形成的泡沫细胞。此外,通过 Western blot 检测主动脉组织和巨噬细胞中 LOX-1 和 NF-κB 的表达。我们的结果表明,薯蓣皂苷不仅降低了血浆脂质、TNF-α、IL-1β 和 IL-6 的水平,还抑制了 AS 大鼠的动脉粥样硬化发展,表现为动脉粥样硬化病变大小和主动脉脂质水平降低。体外研究表明,薯蓣皂苷直接减少泡沫细胞形成,减少细胞内胆固醇积累,并降低 ox-LDL 处理的巨噬细胞中 TNF-α、IL-1β 和 IL-6 的分泌。有趣的是,进一步的研究发现薯蓣皂苷显著降低了主动脉组织和 ox-LDL 处理的巨噬细胞中 LOX-1 和 NF-κB 的表达。总之,我们的研究首次在体内和体外证实了薯蓣皂苷的抗动脉粥样硬化活性。此外,另一个重要发现是薯蓣皂苷介导的 ox-LDL/LOX-1/NF-κB 调节作用,可减轻巨噬细胞 ox-LDL 的摄取和 AS。