Withaferin A

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. This compound binds to Vimentin, the intermediate filament (IF) protein, and causes Vimentin filaments to aggregate in vitro. Furthermore, experiments have demonstrated that Withaferin-induced inhibition of capillary growth in a mouse model of corneal neovascularization was compromised in Vimentin-deficient mice. Additional experiments have reported Withaferin A to be a proteasome inhibitor, with a specific primary target for 20S proteasome β5 subunit. Withaferin A demonstrates the potential to inhibit NFκB activation by prevention of tumor necrosis factor-activated IκB kinase β 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 it's ability to induce regeneration of axons and dendrites and also reconstruct pre and postsynapses in neurons of mice.