Cytoprotective effect of Centella asiatica is mediated through the modulation of mitochondrial voltage-dependent anion channel (VDAC) and scavenging of free radicals

• Leaf extract of Centella asiatica (CA) reduces ischaemia-reperfusion (IR) injury.
• CA quenches reactive oxygen species (ROS) in N2a cells during IR.
• CA prevents the rise of intracellular calcium and attenuates mitochondrial depolarization.
• CA failed to prevent IR injury in VDAC-1 knocked down cells.
• CA increases the conductance of humanVDAC-1 and stabilizes it in the open state.

Centella asiatica (CA) is commonly used as a leafy vegetable in many Asian countries. Consumption of CA is believed to prevent neuronal damage and improve brain function. The protective effect of CA on N2a cells were evaluated using ischaemia-reperfusion (IR) injury and oxygen-glucose deprivation (OGD) models in order to shed light on its molecular mechanism of action. Aqueous-methanolic extract of the CA leaves protected N2a cells against IR injury. CA reduced the levels of intracellular reactive oxygen species (ROS). It also prevented the elevation of intracellular calcium and attenuated the change of mitochondrial membrane potential, caused by OGD. When VDAC-1 was knocked down in N2a cells, CA failed to protect cells against IR injury. Further, CA modulated the properties of human VDAC-1 (hVDAC-1). hVDAC-1, when reconstituted in the lipid bilayer membrane, showed higher conductance after treating with CA. CA stabilized hVDAC-1 in open state, which is possibly associated with its cytoprotective effect.