FIGURE 8.

Schematic illustration of mitochondrial endogenous antioxidant defense system triggered by rhein. 1). Rhein activated the SIRT1/PGC-1α pathway by increasing the expression levels of SIRT1 and PGC-1α. 2). The PGC-1α in the nucleus activated the downstream transcription factor NRF1, and healthy mitochondria were generated by promoted mitochondrial biogenesis. 3). Newly generated healthy mitochondria restored the decreased activity of CytOx in mitochondrial respiratory chain complex IV induced by Aβ_1-42 oligomers, inhibiting the production of ROS. 4). mitochondrial SOD effectively facilitated the elimination of excess ROS. 5). Rhein alleviated the mitochondrial oxidative damage, inhibited the caspase 3-related apoptosis cascade by reducing the release of cyto c from mitochondria, and ultimately, protected neurons from apoptosis.