Abstract
Schisandra chinensis and Evodia rutaecarpa are traditional Chinese herbs that have been used for many years to treat neurodegenerative diseases. In Chinese medicine, multiple herbs are often used in combination to enhance their efficacy, and different combination ratios can produce different therapeutic effects, thus flexibly responding to the needs of various patients. This study aimed to investigate the effects of different ratios of Schisandra and Evodia herbs on learning and memory impairment in rats with Alzheimer's disease (AD) and their specific mechanisms of action. Morris water maze and hematoxylin and eosin (HE) staining experiments were performed to evaluate the effects of different ratios of Schisandra-Evodia on learning memory in AD model rats. Immunohistochemical experiments were performed to investigate the effects of Schisandra-Evodia on the Aβ(1-42) and P-Tau proteins, and protein immunoblotting (WB) was performed to determine the expression of key proteins in two pathways, BDNF/TrkB/CREB and GSK-3β/Tau. Our experimental results show that all Schisandra-Evodia groups showed significant neuroprotective effects, improved learning memory impairment, and reduced levels of Aβ(1-42) and P-Tau proteins in AD model rats. Schisandra-Evodia upregulated BDNF, P-TrkB/TrkB, and P-CREB/CREB protein expression and downregulated GSK-3β and P-Tau/Tau protein expression. Among the different Schisandra-Evodia ratio groups, the 2:1 group showed the strongest therapeutic effect on AD. Our research results indicate that Schisandra-Evodia can reduce Aβ(1-42) and P-Tau protein content by modulating the activity of two pathways, BDNF/TrkB/CREB and GSK-3β/Tau, thus improving neuronal cell damage and cognitive deficits caused by AD. In addition, we found that a Schisandra-Evodia ratio of 2:1 had the most profound therapeutic effect on AD.