ABSTRACT
This study aims to explore the mechanism of Dabugan Decoction in the treatment of generalized anxiety disorder(GAD) based on network pharmacology, molecular docking, and animal experiments. Network pharmacology and molecular docking technology were used to obtain the possible targets and related signaling pathways of Dabugan Decoction in the treatment of GAD. The GAD rat model was established, and the corresponding drugs were given by gavage after randomization. After 28 days of continuous intervention, the anxiety state of rats was detected, and the pathological changes of the hippocampus were detected in each group. ELISA and Western blot were used to detect the protein expression levels of related molecules. A total of 65 drug compounds in Dabugan Decoction were obtained, involving 403 targets of action, 7 398 disease targets of GAD, and 279 common targets of "drug-disease". The key nodes in the protein-protein interaction(PPI) network were Akt1, TNF, IL-6, TP53, IL-1ß, etc. Function analysis of Gene Ontology(GO) and enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG) showed that the PI3K-Akt signaling pathway was the most important pathway. The results of molecular docking showed that the core components of the drug had good binding activity with the corresponding key targets. Animal experiments showed that Dabugan Decoction could effectively improve the anxiety behavior of rats and increase the open arm end movement distance and total distance of rats in the elevated cross labyrinth, the number and stay time of entering the open box, and the time(%) and the number of entering the center of the open field. At the same time, HE staining and Nicil staining showed that the number of hippocampal nerve cells in rats increased, and they were closely arranged. The damage to the cell body was improved, and there was an increase in Nissl substances in the cells. The expression of TNF-α, IL-6, and IL-1ß in rat hippocampus decreased, and the expression of TP53, p-Akt1, and p-PI3K increased. The mechanism may be related to the activation of the PI3K-Akt signaling pathway and the inhibition of inflammatory response. Dabugan Decoction can play a good therapeutic and regulatory role in GAD, reflecting the overall effect of traditional Chinese medicine(TCM) compound and the characteristics of multiple targets and multiple pathways. At the same time, it is preliminarily discussed that the state of GAD may be improved by Dabugan Decoction via-activating PI3K-Akt signaling pathway and inhibiting inflammatory response and anti-apoptosis, thus providing experimental data support for the clinical application of Dabugan Decoction.
Subject(s)
Anxiety Disorders , Drugs, Chinese Herbal , Molecular Docking Simulation , Network Pharmacology , Proto-Oncogene Proteins c-akt , Animals , Rats , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Male , Anxiety Disorders/drug therapy , Anxiety Disorders/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-akt/genetics , Rats, Sprague-Dawley , Signal Transduction/drug effects , Interleukin-6/genetics , Interleukin-6/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Hippocampus/drug effects , Hippocampus/metabolism , Protein Interaction Maps , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , HumansABSTRACT
Molecular immunologic technique gets quick development in recent years, especially the fast development of the immuno-labelling technique, which found its indispensable status in the study of traditional Chinese medicine (TCM). With the development of the study of TCM, medical immunology connecting TCM with the Western medicine has become one of the most indispensable conjunctive subjects. Scientists can study the theories and prevention or treatment mechanisms of TCM not only at holistic and cell levels, but also at molecular and gene levels. Appropriate application of the molecular immunologic techniques according to their characteristics will play an important role in the study of Chinese integrative medicine.