Catalpol induces cell activity to promote axonal regeneration via the PI3K/AKT/mTOR pathway in vivo and in vitro stroke model.

Abstract

To investigate the role and mechanism of catalpol on neuronal cell activity to promote axonal regeneration via PI3K/AKT/mTOR pathway after stroke. In vivo the effect of catalpol (2.5, 5, 7.5 mg/kg; i.p) or vehicle administered 24 h after stroke and then daily for 7 days on behavior, Map-2+/p-S6+ and Map-2+/GAP-43+ immunofluorescence were assessed in a rat model of stroke. Then in vitro, an oxygen-glucose deprivation (OGD/R) model was established to observe the effect of catalpol (0.1, 1, 10 and 100 µg·mL-1) on cultural neurons survive rate, neuronal cell activity and axon growth. Moreover, rapamycin (Rapa) was used to inhibit the mTOR pathway to observe the catalpol mechanism on neuronal cell activity to promote axonal growth, and the proteins related with PI3K/AKT/mTOR pathway were detected by Western blot assay. Repeated treatments with catalpol improved neurological score and significantly enhanced neuronal cell activity, then promote axonal regeneration after stroke. While in vitro, catalpol also increased the survive rate and axonal growth of the neurons. Catalpol can reversed the Rapa inhibited effects on neurons' survive and axon extending. Catalpol can also reversed proteins reduced by Rapa related with PI3K/AKT/mTOR pathway. These results suggested that catalpol might contribute to internal neuronal cell activity and axonal regeneration by regulating PI3K/AKT/mTOR pathway.