Novel Stachydrine-Leonurine Conjugate SL06 as a Potent Neuroprotective Agent for Cerebral Ischemic Stroke.

As major active ingredients of the traditional Chinese medicine motherwort, stachydrine and leonurine were found to have protective effects against cerebral ischemia. However, their bioavailability in vivo was low, and their efficacy was unsatisfactory, which limited their further application. To solve these problems, the conjugates based on the structures of stachydrine and leonurine were designed and synthesized. SL06 was found to have neuronal cell survival improvement, neuronal apoptosis restraining, activation of superoxide dismutase (SOD) activity, and inhibition of lactic dehydrogenase (LDH), reactive oxygen species (ROS), malondialdehyde (MDA) in vitro. In vivo, the infarction size was significantly reduced by SL06 in the middle cerebral artery occlusion rat model. SL06 could also activate protein kinase B (AKT)/glycogen synthase kinase 3β (GSK-3β) activity and promoted the expression of antiapoptoticprotein Bcl-2. On the other hand, the expression of the apoptosis-associated protein cleaved caspase-3 would be inhibited as well. Thus, SL06 as the neuroprotective agent has potential for the treatment of cerebral ischemic stroke.