The Suanzaoren Decoction seems to address Alzheimer's coupled with diabetes through particular ingredients interacting with specific genes involved in disease and therapeutic response.
The study first screened the protein interactors of the main components of Suanzaoren Decoction (SZRD) in the TCMSP database. These protein targets were then cross-referenced with gene candidates influencing both diabetes and Alzheimer's disease, as identified from the Gene Expression Omnibus database. Potentially shared genes were further examined going through a gene-drug-compound-target-disease network and a protein-protein interaction network. The intersecting genes underwent Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses to understand their biological functions and involvement in pathways.
In the discussion of the results, a subset of 1,977 diabetes-related genes and 622 Alzheimer’s-related genes were identified, with 97 found to be common among SZRD, diabetes, and Alzheimer’s disease. Specified compounds within SZRD, namely quercetin, kaempferol, licochalcone a, isorhamnetin, formononetin, and naringenin were proposed to be the active ingredients, primarily interacting with genes such as IL6, TNF, IL1B, CXCL8, IL10, CCL2, ICAM1, STAT3, and IL4. The therapeutic effect of SZRD was demonstrated to be involved in cellular responses to drugs, aging processes, and cellular responses to foreign substances, as well as in cancer and cardiovascular pathways. Molecular docking and molecular dynamics simulations revealed high-affinity binding between several SZRD compounds and the proteins CXCL8, IL1B, and CCL2, indicating the therapeutic potential of these interactions.