Network and Experimental Pharmacology to Decode the Action of Wendan Decoction Against Generalized Anxiety Disorder

Abstract

The mechanism of Wendan Decoction (WDD) against Generalized Anxiety Disorder (GAD) was predicted by network pharmacology and validated by in vivo and in vitro experiments. Methods: The targets of WDD for the treatment of GAD were obtained by a search of online databases. Further, PPI network and KEGG enrichment were used to identify the key targets and pathways. Ultimately, these key targets and pathways were validated by in vivo experiments on GAD mice modeled by repeated restraint stress (RRS) and in vitro experiments on inflammatory factor stimulated BV-2 cells. Results: Through searching the databases, the 137 ingredients of WDD that correspond to 938 targets and 4794 targets related to GAD were identified. Among them, 569 overlapping targets were considered as the therapeutic targets of WDD for GAD. PPI analysis showed that the inflammation-related proteins IL-6, TNF, SRC and AKT1 were the key targets, and KEGG enrichment suggested that PI3K/AKT and MAPK signaling pathways were key pathways of WDD in the treatment of GAD. In vivo experiments, RRS mice exhibited abnormality in behavioristics in open field test (OFT) and elevated plus maze (EPM) and increases in serum corticosterone and the percentage of lymphocytes positive for IL-6 in peripheral blood. These abnormal changes can be reversed by WDD and the positive control drug paroxetine. In vitro experiments, WDD can inhibit IL-6 induced activation of PI3K/AKT and MAPK signaling pathways in BV2 cells, and suppress the ensuing release of inflammatory factors TNF-α, IL-1β and PGE 2 , and showed a dosedependent effect. Conclusion: WDD is able to resist GAD by relieving inflammatory response in peripheral and central system.

Therapeutic effect of Wendan Decoction combined with mosapride on gastroesophageal reflux disease after esophageal cancer surgery

“…Third, WDD inhibited inflammatory cytokines and oxidative stress, thereby reducing the inflammatory response and oxidative damage to the esophageal mucosa. Fourth, WDD can regulate the nervous and endocrine systems, improve the tension and coordination of the lower esophageal sphincter, and prevent the reflux of gastric contents[ 15 - 17 ].…”

Anxiety in oncology outpatients is associated with perturbations in pathways identified in anxiety focused network pharmacology research

“…The PI3K/Akt and MAPK signaling pathways are involved in a variety of biological processes (e.g., protein synthesis, cellular proliferation, cell death [ 53 , 54 ]). Each of these pathways was identified in two of the network pharmacology studies [ 17 , 19 ]. In a review that evaluated anxiety-related microRNAs and their target transcripts, as well as described critical cellular pathways that underlie anxiety processing in the brain [ 53 ], nine anxiolytic and ten anxiogenic anxiety-related microRNAs were identified.…”

“…Seventeen signaling pathways appear to be involved in the mechanisms that underlie the anxiolytic effects of Baihedihuang decoction in patients with breast cancer (Table 1 ). Across the other seven studies, similar analyses were done for Jujebee seed [ 15 ], Rehmannia root and Chinese arborvitae kernel [ 19 ], Roman chamomile [ 16 ], Jiu Wei Zhen Xin formula [ 20 ], rose-bergamot essential oil [ 22 ], Wendan decoction [ 17 ], and Bupleurum [ 21 ]. Across these eight studies, the neuroactive ligand-receptor interaction and the serotonergic synapse pathways were identified as common pathways.…”

The in vivo study on antioxidant activity of wendan decoction in treating hyperlipidemia: a pharmacokinetic-pharmacodynamic (PK-PD) model

“…This prescription is basically prescribed as an “expectorant” in clinical practice. Further, it is commonly used in clinical practice to treat the patients with gallbladder problems and phlegm disturbance such as neurosis, climacteric syndrome and epilepsy ( Che et al, 2016 ; Jin et al, 2022 ). Previous studies have demonstrated the qualitative and quantitative determination of WDD based on LC-MS/MS technology.…”