Child and Family Research Institute, Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, BC, Canada.
J Pharmacol Exp Ther. 2011 Mar;336(3):925-39. doi: 10.1124/jpet.110.172684. Epub 2010 Dec 21.
In this study, we compared the potencies of diosgenin, a plant-derived sapogenin structurally similar to estrogen and progesterone, on vascular smooth muscle functions ranging from contraction and migration to apoptosis. The effects of diosgenin on vascular smooth muscle cell viability and migration were measured using a primary mouse aortic smooth muscle cell culture. The effects of diosgenin on smooth muscle cell contraction and calcium signaling were investigated in the isolated mouse aorta using wire myography and confocal microscopy, respectively. Here, we report that in cultured cells diosgenin (≥ 25 μM) induces apoptosis as measured by the number of annexin V-positive cells and caspase-3 cleavage, while decreasing cell viability as indicated by protein kinase B/Akt phosphorylation. In addition, diosgenin blocks smooth muscle cell migration in a transwell Boyden chamber in response to serum treatment and response to injury in a cell culture system. Diosgenin (≥ 25 μM) also significantly blocks receptor-mediated calcium signals and smooth muscle contraction in the isolated aorta. There is no difference in the inhibitory effects of diosgenin on vascular smooth muscle contraction between the endothelium-intact and endothelium-denuded aortic segments, indicating that they are caused by altered smooth muscle activity. Our findings suggest that over the concentration range of 10 to 15 μM diosgenin may provide overall beneficial effects on diseased vascular smooth muscle cells by blocking migration and contraction without any significant cytopathic effects, implying a potential therapeutic value for diosgenin in vascular disorders.
在这项研究中，我们比较了薯蓣皂素的效力，薯蓣皂素是一种植物衍生的甾体皂甙元，结构上与雌激素和孕激素相似，其对血管平滑肌功能的影响范围从收缩、迁移到细胞凋亡。使用原代小鼠主动脉平滑肌细胞培养物来测量薯蓣皂素对血管平滑肌细胞活力和迁移的影响。通过线描法和共聚焦显微镜分别研究了薯蓣皂素对分离的小鼠主动脉平滑肌细胞收缩和钙信号的影响。在这里，我们报告在培养的细胞中，薯蓣皂素（≥25 μM）诱导细胞凋亡，如 Annexin V 阳性细胞和 caspase-3 切割的数量所测，同时降低蛋白激酶 B/Akt 磷酸化所指示的细胞活力。此外，薯蓣皂素在血清处理和细胞培养系统中损伤反应下阻断平滑肌细胞在 Transwell Boyden 室中的迁移。薯蓣皂素（≥25 μM）还显著阻断分离的主动脉中的受体介导的钙信号和平滑肌收缩。在完整内皮和去内皮的主动脉段中，薯蓣皂素对血管平滑肌收缩的抑制作用没有差异，表明这是由平滑肌活性改变引起的。我们的发现表明，在 10 至 15 μM 的薯蓣皂素浓度范围内，通过阻断迁移和收缩而没有任何明显的细胞病变作用，可能对患病的血管平滑肌细胞提供整体有益的影响，这暗示了薯蓣皂素在血管疾病中的潜在治疗价值。
