Exploring the mechanisms of action of Cordyceps sinensis for the treatment of depression using network pharmacology and molecular docking

Abstract

Background: Depression is the most common type of psychological disorder, with continuous, prolonged, and persistent bad moods as the main clinical feature. Cordyceps sinensis is a complex consisting of the ascospores and bodies of insect larvae from the Hepialidae family that have been parasitized by Cordyceps sinensis militaris. Previous studies have reported that this herb has antidepressant activity. The present study used network pharmacology and molecular docking techniques to investigate the potential antidepressant mechanisms of Cordyceps sinensis.

Methods: The active ingredients of Cordyceps sinensis were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the potential targets were predicted using the PharmMapper platform. The GeneCards database was then used to obtain sub-targets for depression. Common targets were screened and enrichment analyses were performed using the Metascape platform. Finally, the relationship between the active ingredients and the core targets were verified by molecular docking.

Results: Through network pharmacological analysis, 7 active ingredients in Cordyceps sinensis and 41 common targets of drugs and diseases were identified. The active ingredients of Cordyceps sinensis may exert antidepressant effects by acting on important targets such as catalase (CAT), CREB binding protein (CREBBP), epidermal growth factor (EGF), and E1A binding protein P300 (EP300), and by modulating the signaling pathways in which these targets are involved. Subsequently, the core targets were docked to the active ingredients and good binding was observed.

Conclusions: The active ingredients of Cordyceps sinensis may exert antidepressant effects by regulating the CREB binding protein and anti-oxidative stress effects. The foxo signaling pathway (hsa04068), hypoxia-inducible factor 1 (HIF-1) signaling pathway (hsa04066), and Huntington's disease (hsa05016) may be involved in the underlying mechanisms of Cordyceps sinensis. The joint application of network pharmacology and molecular docking provides a new approach to study the mechanisms of action of traditional Chinese medicine. Cordyceps sinensis may play an important role in the future treatment of patients with depression.

Keywords: Cordyceps sinensis; depression; molecular docking; network pharmacology.

Figure 1

A schematic diagram showing the study framework, based on network pharmacology and molecular docking, used to study the antidepressant mechanisms of the active ingredients of Cordyceps sinensis. TCMSP, Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform; GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; PPI, protein-protein interaction.

Figure 2

A Venn diagram showing the common targets between depression and Cordyceps sinensis.

Figure 3

The results of the KEGG enrichment analysis. KEGG, Kyoto Encyclopedia of Genes and Genomes.

Figure 4

The results of the GO enrichment analysis. (A) GO biological processes; (B) GO cellular components; (C) GO molecular functions. GO, Gene Ontology; BP, biological processes; CC, cellular components; MF, molecular functions.

Figure 5

The “drug-compound-target (including PPI)-pathway” network diagram of Cordyceps sinensis for depression. Orange represents Cordyceps sinensis. Green represents compounds. Blue represents the target. Purple represents the pathway. Pink represents depression. PPI, protein-protein interaction.

Figure 6

Molecular docking results with the lowest binding energy. (A) Molecular docking of MOL008998 and CREBBP; (B) molecular docking of MOL008998 and CAT. CAT, catalase.