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 plantderived 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 (Ն25 M) 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 (Ն25 M) 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 M 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.

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“…(8) and by Pan et al(8,23). The results obtained in these experiments are depicted in the online SupplementaryFig.…”

Ca2+ Entry, Oxidative Stress, Ceramide and Suicidal Erythrocyte Death Following Diosgenin Treatment

“…Moreover, diosgenin may foster male fertility [14]. Diosgenin is in part effective by triggering apoptosis [4,5,7,8,10,12,13,. Under appropriate experimental conditions, diosgenin may counteract apoptosis [44].…”

Exploring the impact of a naturally occurring sapogenin diosgenin on underlying mechanisms of Ca2+ movement and cytotoxicity in human prostate cancer cells

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