A retrospective study on professor Gui-Qi Xuan’s experience in traditional Chinese medicine treatment on attention-deficit hyperactivity disorder: based on data mining and network pharmacology

Abstract

Background: To investigate the clinical medication approach of Professor Guiqi Xuan (Prof. Xuan) in treating pediatric patients with attention-deficit hyperactivity disorder (ADHD) and the potential mechanism of the core herbal prescription. Methods: Following medical record information pretreatment, the Traditional Chinese Medicine (TCM) inheritance computing platform system V3.0 was utilized to analyze the standardized data. The associate rules were summarized to identify the core prescription for treating ADHD. The extracted core herbal prescription’s active compounds and potential targets were used to establish a protein-protein interaction network of active ingredient-disease targets. Cytoscape 3.9.1 software was used to analyze the network’s topological parameters to obtain the key active ingredients and their targets. The Bioconductor data package of R4.0.2 was used to analyze the gene ontology biological functions and Kyoto Encyclopedia of Genes and Genomes pathways of key targets. Results: Two hundred and twenty-seven entries derived from TCM record information were selected. Through data mining, it was found that 62.5% of pediatric patients had short-tempered behavior, nearly half had sleep problems, and 30%–40% had picky eating and polyphagia issues. The highest-frequency syndrome type was kidney deficiency and liver hyperactivity. Deficiency, fire, phlegm, and dyspeptic food were the main pathological factors for ADHD. Prof. Xuan’s treatment of ADHD mainly focused on replenishing kidney essence and subduing Yang (active, external, ascending, warm, bright, functional and excited pertain to Yang). The core herbal prescription for ADHD included Yuan-zhi, Yi-zhi, Gui-jia, Bai-shao, Long-chi, Ci-shi, Shi-chang-pu, Yu-jin, Fu-shen, and Huang-jing. The protein-protein interaction network showed that MAOA, ADRB2, FOS, MAOB, and SLC6A3 were the five key targets essential in treating ADHD with core herbal prescriptions. The gene ontology biological function of crucial targets mainly involved G protein-coupled amine receptor activity, catecholamine binding, and neurotransmitter transmembrane transporter activity. Analysis of Kyoto Encyclopedia of Genes and Genomes pathways showed that the dopaminergic synapse signaling and neuroactive ligand-receptor interaction pathways were significantly enriched and may be the primary routes for the main treatment of ADHD. Conclusion: Prof. Xuan’s treatment of ADHD has achieved satisfactory clinical effects by supplementing the kidney, replenishing the essence, opening the orifices, nourishing the Yin (static, internal, descending, cold, dim, organic, depressed and pertain to Yin), and subduing the Yang. The major prescription predominantly affects catecholamine binding, neuroactive ligand-receptor interaction, G protein-coupled amine receptor function, and signaling pathways for dopaminergic synapses. Our findings showed that the methodology and software used in this research could explore and analyze the mechanism behind Prof. Xuan’s clinical medication rule for treating ADHD in children.