Yu and coworkers explored a combination of four active compounds alleviates cerebral ischemia–reperfusion injury in correlation with inhibition of autophagy and modulation of AMPK/mTOR and JNK pathways, while the four compounds combined in a certain ratio (6:9:5:4) they selected according to the optimization condition in animal models not the natural proportion of them in Sheng-mai San (Guo et al., 2014b). This evidence concerns the gene MAPK8 and brain ischemia.