Activation of ATP-sensitive potassium channels as an element of the neuroprotective effects of the Traditional Chinese Medicine MLC901 against oxygen glucose deprivation

NeuroAid (MLC601 and MLC901), a Traditional Medicine used in China for patients after stroke has been reported in preclinical models of ischemia to induce neuroprotection and neuroplasticity. This work shows the effects of MLC901 on an in vitro model of oxygen glucose deprivation (OGD). MLC901 prevents neuronal death induced by 120 min OGD and decreases the exaggerated Ca2+ entry in mature cortical neurons exposed to 120 min OGD. The neuroprotective effect of MLC901 is associated with a large hyperpolarization of ∼20 mV which is antagonized by glibenclamide, the specific inhibitor of KATP channels. In addition MLC901 strengthens the activation of KATP channels. MLC901 has been directly shown to act as an activator of KATP channels as potent as the classical KATP channel opener. The capacity of MLC901 to produce a large hyperpolarization, particularly in neurons that have suffered from energy deprivation probably plays an important role in the neuroprotective effects of this traditional medicine that comes in addition to its previously demonstrated neuroregenerative properties.

► MLC901 prevents neuronal death induced by 2 h Oxygen Glucose Deprivation (OGD). ► MLC901 decreases Ca+ entry induced by glutamate in cortical neurons exposed to OGD. ► The neuroprotective effect of MLC901 is associated with a large hyperpolarization. ► MLC901 strengthens the activation of KATP channels.