A Multi-Target and Multi-Channel Mechanism of Action for Jiawei Yinhuo Tang in the Treatment of Social Communication Disorders in Autism: Network Pharmacology and Molecular Docking Studies

Background. Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder with complex pathogenesis. Currently, the pathogenesis of ASD is not fully understood. Moreover, current treatments do not effectively alleviate the primary symptoms of ASD social disorder (SCDA). Jiawei Yinhuo Tang (JWYHT) is an improved version of the classic prescription Yinhuo Tang. Although this medication has been shown to improve social behavior in ASD patients, the mechanism by which it works remains unknown. Methods. In this study, network pharmacology bioinformatics analysis was used to identify the key targets, biological functions, and signal pathways of JWYHT in SCDA. Then, molecular docking and molecular dynamic simulation were used to validate the activity and stability of the active ingredient and the target protein during the binding process. Results. The analysis identified 157 key targets and 9 core targets of JWYHT (including proto-oncogene (FOS), caspase 3 (CASP3), mitogen-activated protein kinase-3 (MAPK3), interleukin-6 (IL6), mitogen-activated protein kinase-1 (MAPK1), tumor necrosis factor (TNF), mitogen-activated protein kinase-8 (MAPK8), AKT serine/threonine kinase 1 (AKT1), and 5-hydroxytryptamine receptor 1B (5HT1B)) in SCDA. In addition, the Kyoto Encyclopedia of Gene and Genome results, as well as the staggering network analyses, revealed 20 biological processes and 20 signal pathways targeted by JWYHT in SCDA. Finally, molecular docking analysis was used to determine the binding activity of the main active components of JWYHT to the key targets. The binding activity and stability of methyl arachidonate and MAPK8 were demonstrated using molecular dynamics simulation. Conclusion. This study demonstrates that JWYHT regulates neuronal development, synaptic transmission, intestinal and cerebral inflammatory response, and other processes in SCDA.