title: Diosgenin modulates vascular smooth muscle cell function by regulating cell viability, migration, and calcium homeostasis.
abstract: 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.
authors.affiliation: Child and Family Research Institute, Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, BC, Canada. mesfandiarei@gmail.com
authors.forename: Mitra
authors.initials: M
authors.lastname: Esfandiarei
authors.forename: Julia T N
authors.initials: JT
authors.lastname: Lam
authors.forename: Sahar Abdoli
authors.initials: SA
authors.lastname: Yazdi
authors.forename: Amina
authors.initials: A
authors.lastname: Kariminia
authors.forename: Jorge Navarro
authors.initials: JN
authors.lastname: Dorado
authors.forename: Boris
authors.initials: B
authors.lastname: Kuzeljevic
authors.forename: Harley T
authors.initials: HT
authors.lastname: Syyong
authors.forename: Kaiji
authors.initials: K
authors.lastname: Hu
authors.forename: Cornelis
authors.initials: C
authors.lastname: van Breemen
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004144:Diosgenin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
chemical_list: D004144:Diosgenin; D002118:Calcium