Network pharmacology-based study on the mechanism of Schisandra chinensis for treating Alzheimer's disease

Background: Alzheimer's disease (AD) is a mental illness that poses a serious threat to human health worldwide. Schisandra chinensis is a natural herb that can treat the effects of AD, but its specific mechanism is still unclear. The purpose of this study was to explore the potential components and pharmacological pathways of S. chinensis in the treatment of AD.

Materials and methods: In this study, we investigated the compound of S. chinensis and the effects of it on AD by network pharmacology. Meanwhile, the potential mechanism was proved in vitro.

Results: The results showed that S. chinensis contained 173 compounds. Compound-target network confirmed that (E)-9-Isopropyl-6-Methyl-5,9-Decadiene-2-One, 1-Phenyl-1,3-Butanedion, nootkatone and phenyl-2-Propanone were the main chemical constituents which highly aimed at APOE, CACNA1D, GRIN2A, and PTGS2. KEGG and GO enrichment analysis indicated that the main pathways involved neural-related signaling pathways and functions, such as nicotine addiction, GABAergic synapse, Ca²⁺ signaling pathway, AD, and so on. Validation experiments showed that nootkatone was able to exert anti-apoptotic effects related to Ca²⁺ signaling pathway by inhibiting nitric oxide production, enhancing the activity of antioxidant enzymes, upregulating the expression of anti-oxidation and anti-apoptotic proteins in vitro.

Conclusions: These results illustrated that S. chinensis could regulate neuronal apoptosis through the calcium signaling pathway to exert anti-AD by integrating multi-component, multi-target and multi-pathway.

Keywords: Alzheimer's disease; Schisandra chinensis; network pharmacology.