The Effects of Yuan-Zhi Decoction and Its Active Ingredients in Both and Models of Chronic Cerebral Hypoperfusion by Regulating the Levels of A and Autophagy.

Chronic cerebral hypoperfusion (CCH) is closely related to the occurrence of Alzheimer's disease (AD) in the elderly. CCH can induce overactivation of autophagy, which increases the deposition of amyloid- (A) plaques in the brain, eventually impairing the cognitive function. Yuan-Zhi decoction (YZD) is a traditional Chinese medicine (TCM) formulation that is used to treat cognitive dysfunction in the elderly, but the specific mechanism is still unclear. In this study, we simulated CCH in a rat model through bilateral common carotid artery occlusion (BCCAO) and treated the animals with YZD. Standard neurological tests indicated that YZD significantly restored the impaired cognitive function after BCCAO in a dose-dependent manner. Furthermore, YZD also decreased the levels of A aggregates and the autophagy-related proteins ATG5 and ATG12 in their hippocampus. An model of CCH was also established by exposing primary rat hippocampal neurons to hypoxia and hypoglycemia (H-H). YZD and its active ingredients increased the survival of these neurons and decreased the levels of A1-40 and A1-42, autophagy-related proteins Beclin-1 and LC3-II, and the APP secretases BACE1 and PS-1. Finally, both A aggregates showed a positive statistical correlation with the expression levels of the above proteins. Taken together, YZD targets A, autophagy, and APP-related secretases to protect the neurons from hypoxic-ischemic injury and restore cognitive function.