Investigating the active components and molecular mechanism of alpinia officinarum hance therapy against depression by network pharmacology and molecular docking combined with neuroprotective effects in PC12 cells

Depression is a common chronic mood-related disorder characterized by depressed mood, loss of interest, and fatigue. Extract from alpinia officinarum hance (AOH) has shown anti-depressant properties in Bagg Albino/C (BALB/c) mice with depression induced by chronic unanticipated stress. However, the molecular mechanisms underlying the anti-depressant effects of AOH remained unclear. The active ingredients of AOH were acquired via the Traditional Chinese Medicine Systems Pharmacology database and analysis platform (TCMSP), and their corresponding targets were collected from the high-throughput experiment- and reference-guided database of traditional Chinese medicine (HERB). Moreover, the targets associated with depression were identified using the GeneCards database. Common targets between the databases were identified as the anti-depressant targets of AOH. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) was used to build the Protein-Protein Interaction (PPI) network. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analyses were performed using Database for Annotation, Visualization, and Integrated Discovery (DAVID). Using AutoDock Vina and PyMOL software, molecular docking technology was employed to verify whether the main active components in AOH could bind to central targets. Finally, the CCK8 assay was used to analyze the activity of AOH extract on PC12 cells and depression model cells induced by corticosterone (CORT). The expression was checked via the Quantitative Real - Time Polymerase Chain Reaction (qRT-PCR) of key target molecules. After a successful screening of 10 active components in AOH, it was demonstrated that these compounds had strong relationships with 115 targets associated with depression, among which Interleukin - 6 (IL6), RAC - alpha serine/threonine - protein kinase (AKT1), Interleukin - 1 beta (IL1B), tumor necrosis factor (TNF), Epidermal Growth Factor Receptor (EGFR), and Tumor protein p53 (TP53) could be the potential targets for treating depression. GO and KEGG enrichment pathway analysis yielded 416 terms and 153 pathways, respectively. Quercetin, kaempferol, sitosterol, medicarpin, and galangin were the key active components of AOH involved in treating depression. Molecular docking indicated the screened target proteins had good binding activity with active components with affinity values < 5 kcal/mol. AOH extract was non-cytotoxic to PC12 cells and had a good protective effect on the depression cell model. The qRT-PCR analysis showed that the AOH extract can restore EGFR, TP53, and IL1B levels in CORT-induced PC12 cells to normal. Totally Quercetin, kaempferol, sitosterol, medicarpin, and galangin were identified as possible active ingredients in AOH that could potentially treat depression. The antidepressant benefits of AOH may stem from its capacity to modulate neuroinflammation.