A network pharmacology analysis on drug-like compounds from Ganoderma lucidum for alleviation of atherosclerosis

Ganoderma lucidum (GL) is known as a potent alleviator against chronic inflammatory disease like atherosclerosis (AS), but its mechanisms against AS have not been unveiled. This research aimed to identify the key compounds(s) and mechanism(s) of GL against AS through network pharmacology. The compounds from GL were identified by gas chromatography-mass spectrum (GC-MS), and SwissADME screened their physicochemical properties. Then, the target(s) associated with the screened compound(s) or AS related targets were identified by public databases, and we selected the overlapping targets using a Venn diagram. The networks between overlapping targets and compounds were visualized, constructed, and analyzed by RStudio. Finally, we performed a molecular docking test (MDT) to explore key target(s), compound(s), on AutoDockVina. A total of 35 compounds in GL were detected via GC-MS, and 34 compounds (accepted by Lipinski's rule) were selected as drug-like compounds (DLCs). A total of 34 compounds were connected to the number of 785 targets, and DisGeNET and Online Mendelian Inheritance in Man (OMIM) identified 2,606 AS-related targets. The final 98 overlapping targets were extracted between the compounds-targets and AS-related targets. On Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, the number of 27 signaling pathways were sorted out, and a hub signaling pathway (MAPK signaling pathway), a core gene (PRKCA), and a key compound (Benzamide, 4-acetyl-N-[2,6-dimethylphenyl]) were selected among the 27 signaling pathways via MDT. Overall, we found that the identified 3 DLCs from GL have potent anti-inflammatory efficacy, improving AS by inactivating the MAPK signaling pathway. PRACTICAL APPLICATIONS: Ganoderma lucidum (GL) has been used as a medicinal or edible mushroom for chronic inflammatory patients: diabetes mellitus and dyslipidemia, especially atherosclerosis (AS). Until now, the majority of mushroom research has been implemented regarding β-glucan derivatives with very hydrophilic physicochemical properties. It implies that β-glucan or its derivatives have poor bioavailability. Hence, we have involved GC-MS in identifying lipophilic compounds from GL, which filtered them in silico to sort drug-like compounds (DLCs). Then, we retrieved targets associated with the DLCs, and identified a key signaling pathway, key targets, and key compounds against AS. In this paper, we utilized bioinformatics and network pharmacology theory to understand the uncovered pharmacological mechanism of GL on AS. To sum things up, our analysis elucidates the relationships between signaling pathways, targets, and compounds in GL. Ultimately, this work provides biochemical evidence to identify the therapeutic effect of GL on AS, and a scientific basis for deciphering the key mechanism on DLCs of GL against AS.