Ginsenoside Re Rescues Methamphetamine-Induced Oxidative Damage, Mitochondrial Dysfunction, Microglial Activation, and Dopaminergic Degeneration by Inhibiting the Protein Kinase Cδ Gene

Ginsenoside Re, one of the main constituents of Panax ginseng, possesses novel antioxidant and anti-inflammatory properties. However, the pharmacological mechanism of ginsenoside Re in dopaminergic degeneration remains elusive. We suggested that protein kinase C (PKC) delta mediates methamphetamine (MA)-induced dopaminergic toxicity. Treatment with ginsenoside Re significantly attenuated methamphetamine-induced dopaminergic degeneration in vivo by inhibiting impaired enzymatic antioxidant systems, mitochondrial oxidative stress, mitochondrial translocation of protein kinase C delta, mitochondrial dysfunction, pro-inflammatory microglial activation, and apoptosis. These protective effects were comparable to those observed with genetic inhibition of PKC delta in PKCd knockout (-/-) mice and with PKC delta antisense oligonucleotides, and ginsenoside Re did not provide any additional protective effects in the presence of PKC delta inhibition. Our results suggest that PKC delta is a critical target for ginsenoside Re-mediated protective activity in response to dopaminergic degeneration induced by MA.