背景:麦冬,临床上常用的治疗心血管疾病的中药,回到胃里,肺和心经络.据报道,这是滋阴,润肺,用于治疗心阴虚证和心肺虚弱,这表明麦冬可能对心脏疾病有保护作用。动脉粥样硬化是心血管疾病发生发展的重要过程,脂质异常沉积诱导的巨噬细胞泡沫细胞是其重要基础。我们先前的研究表明,麦冬提取物(EOR)在体外可以改善动脉粥样硬化。然而,它可能通过抑制巨噬细胞泡沫细胞的形成来预防心血管疾病,其潜在的有效成分和机制尚不清楚。
目的:本研究旨在探讨麦冬对巨噬细胞泡沫细胞形成的影响及其潜在活性成分和作用机制。
方法:采用Ox-LDL诱导的巨噬细胞来评价麦冬对巨噬细胞泡沫细胞形成的影响。然后通过生物特异性细胞提取筛选抑制巨噬细胞泡沫细胞形成的潜在活性成分,并通过Westernblot探索其潜在机制。
结果:发现麦冬提取物能显著抑制巨噬细胞泡沫细胞的形成,巨噬细胞中TG和TC和油红O染色分析的降低证明,这表明EOR减少了巨噬细胞泡沫细胞的形成。同时,EOR显示增加巨噬细胞的抗氧化能力。用EOR治疗后,确定了与巨噬细胞泡沫细胞特异性相互作用的两个潜在活性成分,以抑制巨噬细胞泡沫细胞的形成,包括羟甲基孕酮A和羟甲基孕酮B。然后证明甲基孕酮A降低了CD36,Lox-1和SREBP2的表达,明显增加了ABCA1的表达。ABCG1和SREBP1的表达无变化。
结论:在我们的研究中,发现麦冬通过抑制ox-LDL诱导的巨噬细胞泡沫细胞形成而具有抗动脉粥样硬化的作用,并通过生物特异性细胞提取鉴定出了两种潜在的化合物,包括羟萘酚酮A和羟萘酚酮B。证明了甲基吡罗酮A通过减少摄取来抑制泡沫细胞,合成和增加外排,为麦冬的应用和中药有效成分的研究提供指导和参考。
BACKGROUND: Ophiopogonis Radix, the commonly used traditional Chinese medicine in clinic for treating cardiovascular diseases, is returned to the stomach, lung and heart meridian. It is reported to nourish yin, moisten lung and is used to treat heart yin deficiency syndromes and asthenia of heart and lung, which indicated that Ophiopogonis Radix may have a protective effect on heart disorders. Atherosclerosisis is an important process in the development of cardiovascular diseases and abnormal lipid deposition induced macrophage foam cells is its crucial foundation. Our previous study showed the extract of Ophiopogonis Radix (EOR) ameliorates atherosclerosis in vitro. However, it may protect against cardiovascular diseases through inhibiting macrophage foam cell formation and its potential effective components and mechanisms are still unclear.
OBJECTIVE: Our study aimed to investigate the effect of Ophiopogonis Radix on macrophage foam cell formation and its potential active constituents and mechanisms.
METHODS: Ox-LDL induced macrophage cells were employed to evaluate the effect of Ophiopogonis Radix on macrophage foam cell formation. Then the potential active constituents inhibited formation of macrophage foam cells were screened by biospecific cell extraction and its underlying mechanisms were also explored by Western blot.
RESULTS: The extract of Ophiopogonis Radix was found to significantly inhibit macrophage foam cell formation, evidenced by the decrease of TG and TC and Oil Red O staining analysis in macrophage cells, which indicated that EOR reduced the formation of macrophage foam cells. At the same time, EOR was showed to increase antioxidant capacity in macrophage cells. After treatment with EOR, two potential active components interacted with macrophage foam cells specifically were identified to inhibit macrophage foam cell formation including methylophiopogonanone A and methylophiopogonanone B. Methylophiopogonanone A was then proved to decrease the expression of CD36, Lox-1 and SREBP2, increase the expression of ABCA1 obviously, while the expression of ABCG1 and SREBP1 had no changes.
CONCLUSIONS: In our study, Ophiopogonis Radix was found to protect against atherosclerosis through suppressing ox-LDL induced macrophage foam cell formation and two potential compounds were identified by biospecific cell extraction including methylophiopogonanone A and methylophiopogonanone B. Moreover, methylophiopogonanone A was proved to inhibit foam cells through reducing uptake, synthesis and increasing efflux, which may provide guidance and reference for application of Ophiopogonis Radix and investigation of the effective components of TCMs.