Network pharmacology-based active compounds and pharmacological mechanisms of ginseng for depression in post-COVID-19

Abstract

<jats:title>Abstract</jats:title> <jats:p><jats:bold>Introduction:</jats:bold> The novel coronavirus disease 2019 (COVID-19) is in the midst of worldwide panic. Sudden onset of an immediate life-threatening illness, quarantine and unemployment caused by epidemic are all contributors to depression. Ginseng has been reported to be an effective and safe clinical treatment on both immune-regulation and anti-depression. However, the mechanism of its anti-depression effect has not been fully characterized. In order to provide theoretical guidance for further clinical application in post-pandemic, we investigated active compounds and pharmacological mechanisms of ginseng to exert anti-depressant activity using network pharmacology, and discussed the active ingredients with immune-regulation and anti-depression.<jats:bold>Methods:</jats:bold> Information on compounds in ginseng was obtained from public databases, and genes related to depression were gathered using the GeneCards database. Networks of ginseng-associated targets and depression-related genes were constructed through STRING database. Potential targets and pathway enrichment analysis related to the therapeutic efficacy of ginseng for depression were identified using Cytoscape and Database for Annotation, Visualization and Integrated Discovery (DAVID). <jats:bold>Results:</jats:bold> Network pharmacological analysis of ginseng in treatment of depression identified 16 active ingredients, 47 potential targets, 32 GO terms, and 8 target gene-regulated major pathways. Among them, kaempferol, beta-sitosterol, stigmasterol, fumarine and frutinone A are bioactive compounds and key chemicals. Core genes in PPI network were AKT1, CASP3, NOS3, TNF, and PPARG. Enrichment results revealed that ginseng could regulate multiple aspects of depression through neuroactive ligand-receptor interaction, HIF-1 signaling pathway, and Serotonergic synapse. More importantly, we found that frutinone A and kaempferol are key ingredients in ginseng with dual activities of immune-regulation and anti-depression. <jats:bold>Conclusions:</jats:bold> We discovered that the therapeutic activities of ginseng for depression mainly involve neurotransmitters, neurotrophic factors, neurogenesis, HPA axis and inflammatory response. Pharmacological network analysis can help to explain the potential effects of ginseng for treating depression, indicating that ginseng is a preferable herb clinically for immune-regulation and anti-depression in post-pandemic.</jats:p>

Ginseng: Pharmacological Action and Phytochemistry Prospective

“…Neutral and acid polysaccharides are present in ginseng. These polysaccharides attribute pharmacological activity as immunomodulating, antioxidant, anti-depressant anticancer, anti-inflammatory, and antiproliferative activities by playing a vital role on nervous system disorders through regulation of signaling pathway, immune system and inflammatory response [10]. Two bioactive ginseng polysaccharides named GP50-dHR and GP50eHR showed antidiarrheal effects [11].…”

Bioinformatics Exploration of Ginseng: A Review

“…Zhang et al [49] have reported ginsenoside, stigmasterol, β-sterol, β-elemene and β-selinene, kaempferol, panaxynol, ginsenoyne A, fumarine, girinimbin, elemicin, dauricine, and maltol, as part of secondary metabolites produced by ginseng. However, network analysis of ginseng-associated targets ginseng in treatment of depression which could occur in post-COVID19 period, identified AKT1, CASP3, NOS3, TNF, and PPARG as the core genes in protein-protein interaction network, and that ginsenoside Re, ginsenoside Rg1, frutinone A and kaempferol were the key ingredients in ginseng for immune-regulation [50].…”