RT Journal Article T1 Diosgenin Modulates Vascular Smooth Muscle Cell Function by Regulating Cell Viability, Migration, and Calcium Homeostasis A1 Esfandiarei, Mitra A1 Lam, Julia A1 Abdoli Yazdi, Sahar A1 Kariminia, Amina A1 Navarro Dorado, Jorge A1 Kuzeljevic, Boris A1 Syyong, Harley A1 Hu, Kaiji A1 van Breemen, Cornelis AB 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. PB American Society for Pharmacology and Experimental Therapeutics (ASPET) SN 0022-3565 YR 2010 FD 2010 LK https://hdl.handle.net/20.500.14352/100579 UL https://hdl.handle.net/20.500.14352/100579 LA eng NO Esfandiarei M, Lam JT, Yazdi SA, Kariminia A, Dorado JN, Kuzeljevic B, Syyong HT, Hu K, van Breemen C. Diosgenin modulates vascular smooth muscle cell function by regulating cell viability, migration, and calcium homeostasis. J Pharmacol Exp Ther. 2011 Mar;336(3):925-39. doi: 10.1124/jpet.110.172684. Epub 2010 Dec 21. PMID: 21177478. DS Docta Complutense RD 25 dic 2025