Abstract

This study aims to explore the mechanism of action of spleen-tonifying herbs in the spleen-tonifying and spasm-alleviating decoction for treating tic disorders based on network pharmacology and mitochondrial metabolism. Active ingredients and targets of spleen-tonifying herbs were collected from the Traditional Chinese Medicine Systems Pharmacology database. Tic disorder related targets were obtained from Online Mendelian Inheritance in Man, GeneCards, Therapeutic Target database and DisGeNet databases and the intersection targets of drugs and diseases were obtained using Venn diagram. Key targets were obtained through Search Tool for the Retrieval of Interacting Genes/Proteins database to construct a protein-protein interaction network, followed by gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis using the MetaScape online platform. 25 healthy specific pathogen free-grade Sprague-Dawley male rats of 3 w old, were randomly divided into five groups, model group, Western medicine group, spleen-tonifying and spasm-alleviating decoction group, spleen-tonifying herb group and blank control group, with 5 rats in each group. Rats in each group were orally administered interventions at a dose of 1 ml/100g body weight/day for 4 w. Rats in the blank control and model groups were given physiological saline; rats in the Western medicine group were given metoclopramide hydrochloride suspension; rats in the spleen-tonifying herb group were given the spleen-tonifying herb formula and rats in the spleen-tonifying and spasm-alleviating decoction group were given the decoction. The content of mitochondrial respiratory chain enzyme complex IV and sodium-potassium-adenosine triphophatase enzyme in rats were detected. Spleen-tonifying herb group may exert its effects on neurotransmitter regulation, anti-inflammation, regulation of apoptosis, reduction of mitochondrial damage, and protection of neurons through core active ingredients such as baicalein, beta-sitosterol and stigmasterol. Core targets regulate signalling pathways, thereby exerting the spleen-tonifying effects against spasms. Iminodipropionitrile induced tic disorder rats showed a tendency of growth retardation while metoclopramide hydrochloride, spleen-tonifying herb group, and spleen-tonifying and spasm-alleviating decoction group showed acceleration of the growth and development of model rats. However, short-term treatment of 1 mo did not significantly improve the growth and development of tic disorder rats. Spleen-tonifying therapy may provide a new direction for the treatment of tic disorder.