Hu-Ping Wang,1– 3,* Ming-Cheng Li,4,* Jiao Yang,1 Jun Zhou,5 Zhi-Peng Meng,1 Yun-Yun Hu,1 Yu-Jie Lyu,1 Yi-Qin Chen,1 Yu-Mei Han,1 Wen-Li Pei1 

1School of Basic Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, People’s Republic of China; 2Key Laboratory of Traditional Chinese Herbs and Prescription Innovation and Transformation of Gansu Province, Gansu University of Traditional Chinese Medicine, Lanzhou, People’s Republic of China; 3Laboratory for TCM New Products Development Engineering of Gansu Province, Lanzhou, People’s Republic of China; 4Traditional Chinese Medicine Pain Rehabilitation Department, the 69th Hospital of Qujing City, Qujing, People’s Republic of China; 5Preventive Medicine Department, Xichang Hospital of Traditional Chinese Medicine, Xichang, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Hu-Ping Wang, Gansu University of Traditional Chinese Medicine, 35 Dingxi East Road, Lanzhou, People’s Republic of China, Email whp@gszy.edu.cn

Background: Apoptosis and immune inflammation play important roles in the pathological process of Alzheimer’s disease (AD), but their specific pathogenesis is still unclear. Therefore, this article focuses on exploring the effects of Danzhi Xiaoyao Powder (DXP) on the learning and memory ability of AD model rats from the dual mechanisms of apoptosis and immune inflammation.
Methods: The AD model was replicated by injecting Okadaic acid (100 ng) into the bilateral hippocampus of rats. Successful rats were selected and orally administered with donepezil hydrochloride and DXP decoction for 42 days. Their learning and memory abilities, hippocampal morphology, Aβ expression, inflammatory factors, apoptotic factors, anti apoptotic factors, as well as the expression of pathway proteins and mRNA were detected.
Results: After DXP intervention, the learning and memory abilities of rats improved, the neuronal cell arrangement was more complete, the expression of Aβ decreased, the expression of pro-inflammatory cytokine and apoptotic factors decreased, the expression of anti apoptotic factors increased, Protein Kinase B (Akt) expression and activity significant up-regulation, and nuclear factor kappa-B (NF-κB), p38 MAPK (p38), MAPKAPK-2 (MK2), Cyclooxygenase-2 (COX-2) protein and mRNA expression were significantly down-regulated.
Conclusion: DXP can improve the learning and cognitive abilities of AD model rats, and its mechanism of action may be related to the regulation of the Akt/NF-κB apoptosis pathway mediated by NF-κB interaction and the p38MAPK/MK2/COX-2 immune inflammatory dual pathway.

Keywords: Alzheimer’s disease, Danzhi Xiaoyao powder, Akt/NF-κB signaling pathway, P38MAPK/MK2/COX2 signaling pathway, neuronal apoptosis, neuronal specific inflammatory response