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

Abstract

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.

Qizhi Kebitong Formula Ameliorates Streptozocin-Induced Diabetic Osteoporosis through Regulating the PI3K/Akt/NF-κB Pathway

“…Furthermore, the differentiation of osteoblasts was regulated by TNF- α , which was the earliest inflammatory mediator produced in response to oxidative stress and promoted the production of inflammatory cytokines to promote osteoblast apoptosis [ 39 , 40 ]. In addition, accumulating studies have revealed that the expressions of core targets, including Akt1, TNF- α , IL-6, and RELA, made the vital functions in regulating inflammatory response [ 41 , 42 ]. We have verified that QKF could regulate the key targets and PI3K/Akt/NF- κ B signaling pathway to explain the molecular mechanism of QKF treatment on DOP.…”

Exploring the Potential Mechanism of Danshen in the Treatment of Concurrent Ischemic Heart Disease and Depression Using Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation

“…The RMSD reflects the movement of protein-ligand complexes during MDS. 34 The RMSD of the AKT1-tanshinone IIA backbone-backbone stabilized after 2 ns with a mean value of 0.234 ± 0.043 nm; the RMSD of the MMP9-luteolin backbone-backbone stabilized after 1 ns with a mean value of 0.194 ± 0.0189 nm. The RMSD of the AKT1-tanshinone IIA ligand-ligand was stable after 1 ns with a range of 0.032 ± 0.009 nm.…”