Unveiling the multitarget mechanism of Liuwei Dihuang decoction in autism spectrum disorder via network pharmacology and molecular docking

Liuwei Dihuang decoction (LW) is used for paediatric autism spectrum disorders (ASD) treatment, but its mechanism of action is unclear. This study aims to provide clinical evidence for LW in treating ASD in children and investigate its mechanism through network pharmacology, microarray analysis, and molecular docking. A retrospective review of 80 clinical cases of children with ASD and the therapeutic effect of LW was conducted. Drug-disease co-expressed genes were used to construct PPI network maps. The active ingredients of LW were obtained from the TCMSP, CNKI, and PubMed, with screening criteria of OB ≥ 30% and DL ≥ 0.18. Disease targets were sourced from the GeneCards, OMIM, and DisGeNET databases. Core targets were further analyzed using GO and KEGG. Microarray data were employed to analyze the expression levels of the core targets. Molecular docking and dynamics simulations were performed on protein-ligand complexes. MD simulations were performed using GROMACS 2022 for 100 ns, and the stability of the complex was evaluated by analyzing key parameters including RMSD, RMSF, and hydrogen bond occupancy. LW showed promising therapeutic effects on ASD, with efficacy decreasing with age. Quercetin, Tetrahydroalstonine, Diosgenin and Kaempferol were identified as active compounds. PTGS2 and MMP9 were upregulated and identified as key genes in ASD treatment. The binding energies of the key complexes PTGS2-Quercetin, PTGS2-Tetrahydroalstonine, MMP9-Diosgenin, and MMP9-Kaempferol were determined to be - 9.5 kJ/mol, - 9.4 kJ/mol, - 8.1 kJ/mol, and - 7.2 kJ/mol, respectively. Molecular simulations showed favorable binding between key genes and active compounds. This study provides clinical evidence for the treatment of ASD with LW, and predicts its main active ingredients, potential pathways, and core targets, providing a reliable basis for the clinical treatment and drug screening of ASD.