Achyranthes bidentata polypeptide k improves long-term neurological outcomes through reducing downstream microvascular thrombosis in experimental ischemic stroke.

Achyranthes bidentata Bl. (A. bidentata) occupies an important position in traditional Chinese medicine owing to the property of promoting the circulation of blood and removing stasis. Achyranthes bidentata polypeptide k (ABPPk) is one of the active components isolated from A. bidentata.We previously demonstrated that ABPPk has potent neuroprotective effects against neuronal apoptosis both in vitro and in vivo, but the roles and mechanisms of ABPPk on long-term functional recovery after ischemic stroke remain unknown. In the current study, we investigated the neuroprotective effects of ABPPk on filament transient middle cerebral artery occlusion (tMCAO) rats and found that ABPPk reduced the infarct volume and maintained the neuronal integrity in the ischemic penumbra. Moreover, we found that ABPPk might reduce the formation of downstream microthrombus through preventing ischemic-induced oxidative damage of brain endothelial cells and activation of tissue factor (TF), plasminogen activator inhibitor-1 (PAI-1), and NF-κB. ABPPk also inhibited polymorphonuclearleukocytes(PMNs) infiltration and matrix metalloproteinase-2/-9 (MMP-2/-9) activation in the ischemic penumbra. Morris water maze, foot fault test, and modified neurological severity score were assessed for a period of 6 weeks following tMCAO. ABPPk improved long-term recognition abilities and neurological outcomes after stroke compared with saline-treated rats. Taken together, these results suggested that ABPPk is beneficial to the improvement of long-term outcomes after transient cerebral ischemia injury and can be used as a potential neuroprotective agent.