Investigating the role of miR-26b-5p and PTGS2 in schizophrenia treatment using Wendan decoction: Network pharmacology and experimental validation

This study aims to identify the target of action of Wendan decoction, a classical Chinese herbal formula used for the treatment of psychiatric disorders, specifically schizophrenia, using network pharmacology. Traditional Chinese Medicine (TCM) bioinformatics and network pharmacology were employed to predict the genes regulated by miR-26b-5p and identify the active ingredients and related targets of the Wendan decoction from public databases. Key components and targets were screened by constructing a "TCM-component-target" network, followed by pathway enrichment analysis of the related targets. The expression levels of miR-26b-5p and prostaglandin-endoperoxide synthase 2 (PTGS2) in the peripheral blood of patients with schizophrenia patients and healthy individuals were determined using RT-qPCR. Molecular docking was performed to explore the interaction between the active ingredients of the Wendan decoction and key differentially expressed molecules, investigating the role of miR-26b-5p in the treatment of schizophrenia with the Wendan decoction. A total of 135 active constituents were extracted from the Wendan decoction, and 144 molecules, including PTGS2 and other derivatives, were screened for drug-target and disease-target inter-mapping. Compared to peripheral blood samples from healthy controls and patients with depression, peripheral blood samples from patients with schizophrenia patients showed low miR-26b-5p expression and elevated PTGS2 expression, with no significant difference observed in the expression between healthy controls and patients with depression. Molecular docking revealed that several active compounds were found in five of the six constituents of the Wendan decoction bound with PTGS2. Pathway enrichment analysis suggested that the Wendan decoction may have a potential therapeutic role in treating schizophrenia by regulating the circadian rhythm, N-methyl-D-aspartate glutamate receptor activity, inflammatory mediator regulation of transient receptor potential channels, and other pathways implicated in schizophrenia. Wendan decoction may treat schizophrenia via the miR-26b-5p targeting factor PTGS2 and inflammation-related pathways. miR-26b-5p, combined with PTSG2, holds the potential as a differential diagnostic marker for schizophrenia.