Withaferin A, a steroidal lactone originally purified from Withania somnifera, has been shown to have potent antiangiogenesis activity in vivo as well as potent growth inhibitory activities. Withaferin A binds to Vimentin, the intermediate filament (IF) protein, and causes Vimentin filaments to aggregate in vitro. Furthermore, experiments have demonstrated that Withaferin-A induced inhibition of capillary growth in a mouse model of corneal neovascularization in Vimentin-deficient mice. Additional experiments have reported Withaferin A to be a proteasome inhibitor, with a specific primary target for 20S proteasome 5 subunit. Withaferin A demonstrates the potential to inhibit NF B activation by prevention of tumor necrosis factor-activated I B kinase via a thioalkylation-sensitive redox mechanism. In other studies, Withaferin A was also observed to alter cytoskeletal architecture by covalently binding Annexin II and stimulating its basal F-actin cross-linking activity. Another characteristic of Withaferin A that has been noted is its ability to induce regeneration of axons and dendrites and also reconstruct pre and postsynapses in neurons of mice. Withaferin A is also known as NSC 101088, NSC 273757, and 5β,6β-epoxy-4β,22R,27-trihydroxy-1-oxo-δ-lactone-ergosta-2,24-dien-26-oic acid.
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