A network pharmacology analysis on drug-like compounds from Ganoderma lucidum for alleviation of Atherosclerosis
Abstract Background: Ganoderma lucidum (GL) is known as a potent alleviator against chronic inflammatory disease like atherosclerosis (AS), but its critical bioactive compounds and their 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.Methods: The compounds from GL were identified by gas chromatography-mass spectrum (GC-MS), and SwissADME screened their physicochemical properties. Then, the gene(s) associated with the screened compound(s) or AS related genes were identified by public databases, and we selected the overlapping genes using a Venn diagram. The networks between overlapping genes and compounds were visualized, constructed, and analyzed by RStudio. Finally, we performed molecular docking test (MDT) to identify key gene(s), compound(s) on AutoDockVina.Results: A total of 35 compounds in GL was detected via GC-MS, and 34 compounds (accepted by the Lipinski's rule) were selected as drug-like compounds (DLCs). A total of 34 compounds were connected to the number of 785 genes and 2,606 AS-related genes were identified by DisGeNET and Online Mendelian Inheritance in Man (OMIM). The final 98 overlapping genes were extracted between the compounds-genes network and AS-related genes. 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. Conclusion: Overall, we found that the identified 3 DLCs from GL have potent anti-inflammatory efficacy, improving AS by inactivating the MAPK signaling pathway.