Ginsenoside Rg1 improves ischemic brain injury by balancing mitochondrial biogenesis and mitophagy

Abstract

Purpose: To study the effects of ginsenoside Rg1 on mitochondrial dysfunction  induced by ischemic stroke.
Methods: Human neuroblastoma SK-N-SH cells, subjected to oxygen-glucose  deprivation (OGD), were divided into six groups: control group, OGD group, 3 OGD + Rg1 groups (6.25, 12.5 and 25 μM), and Rg1 (25 μM) group. Apoptosis rate, intracellular production of reactive oxygen species (ROS), and mitochondrial transmembrane potential (MTP) in the OGD cells treated with different  concentrations of Rg1 were determined. The mRNA and protein expression levels of mitochondrial biogenesis-related transcription factors and autophagy-related proteins were determined by reat time-polymerase chain reaction (RT-PCR) and Western blotting.
Results: ROS production was significantly increased in OGD SK-N-SH cells (p < 0.01), but this was reversed by Rg1 treatment (p < 0.05). Rg1-treated cells had significantly higher MTP when compared with OGD cells (p < 0.01). Rg1 treatment led to significant increases in mRNA and protein expression levels of PGC1-α, NRF-1, and TFAM-1 (p < 0.01). Moreover, Rg1 treatment inhibited apoptosis in SKN- SH cells, and up-regulated autophagy-related proteins in t neuronal injury model. Treatment with autophagy inhibitors decreased the mitochondrial protective effects exerted by Rg1 in OGD SK-N-SH cells.
Conclusion: Rg1 improves mitochondrial dysfunction by regulating autophagy in mitochondria. Thus, it may offer protection from brain injuries caused by cerebral ischemia.

 Keywords: Cerebral ischemia, Ginsenoside Rg1, Mitochondrial dysfunction, Mitophagy