SMAD2 and Alzheimer disease: Icariin, the major constituent of flavonoids from Epimedium brevicornum, has demonstrated a relevant neuroprotective activity in animal models of AD as well as the ability to ameliorate the cognitive deficits induced by permanent occlusion of bilateral common carotid arteries (BCCAO) by reducing the BCCAO-induced TGF-β1 over-expression and Smad2/3 phosphorylation [86].