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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- β  (A β ) 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 β  aggregates and the autophagy-related proteins ATG5 and ATG12 in their hippocampus. An  in vitro  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 A β 1-40 and A β 1-42, autophagy-related proteins Beclin-1 and LC3-II, and the APP secretases BACE1 and PS-1. Finally, both A β  aggregates showed a positive statistical correlation with the expression levels of the above proteins. Taken together, YZD targets A β , autophagy, and APP-related secretases to protect the neurons from hypoxic-ischemic injury and restore cognitive function.

evidence-based complementary and alternative medicine

The Effects of Yuan-Zhi Decoction and Its Active Ingredients in Both In Vivo and In Vitro Models of Chronic Cerebral Hypoperfusion by Regulating the Levels of Aβ and Autophagy