Immunity Enhancement Activity and Mechanism of Ganoderma lucidum-Panax quiquefolium L.-Cordyceps sinensis compound Based on Network Pharmacology

In this study, the immunity enhancement activity of Ganoderma lucidum-Cordyceps sinensis-Panax quiquefolium L. compound (here in after referred to as "compound") was systematically evaluated, and its mechanism was explored by network pharmacology. The NK cell activity, delayed allergic reaction, spleen lymphocyte proliferation and monocyte-macrophage phagocytosis of compound were investigated to evaluate its immunity enhancement activity. The results in vivo and in vitro indicated the low, medium and high dose groups (0.4, 0.8, 2.4 g/kg) of compound could significantly increase NK cell activity (P<0.001), the medium and high dose groups could significantly increase the delayed allergic reaction activity (P<0.001), and the low dose group could significantly increase the phagocytic index of monocyte-macrophage (P<0.05). The active ingredients, action targets and disease targets of the compound were collected by multiple online databases and document retrieval. Cytoscape and STRING were utilized to construct the interaction network between compound-target-disease network and protein, GO and KEGG enrichment analysis of target genes performed by Metascape. The results of network pharmacological analysis indicated that the compound could act on 94 targets such as protein kinase B (AKT1), epidermal growth factor receptor (EGFR) and non-receptor tyrosine kinase (SRC) of NK cells and T cells by active substances such as arachidonic acid, peroxyergosterol, cholesterol palmitate, PQ-2, epoxy ganoderma alcohol C, ergosterol-7,9,22-triene-3-alcohol, ergosteran-7,22-diene-3β-alcohol and other active compounds, regulate 1382 GO items, including tumor regulation, FOXO, Th17 and NK cells and 171 signal channel to synergistically enhance immunity. Meanwhile, this study preliminarily revealed the synergistic mechanism of multi-components, multi-targets and multi-pathways of the compound to immunity enhancement, which could provide new ideas and theoretical basis for further study in its molecular mechanism and application.