The qualitative and quantitative analysis of Ganoderma lucidum spore powder chemical compounds as p38 MAPK inhibitors by the generation and verification of pharmacophore modelling

Ganoderma lucidum spore powder (GLSP), a high-value health food and medicine, has attracted widespread attention for its biological components and abundant pharmacological activities. However, the chemical component classification, fragmentation patterns, fatty acid quantification and biological activities of GLSP against p38 MAPK have not been clearly articulated. In the present study, a total of 142 chemical compounds were identified in GLSP by UPLC-Orbitrap-HRMS, including 55 lipids (3 glycerides, 21 phospholipids, 4 glycolipids, 5 sterols, 22 fatty acids), 25 triterpenes, 10 alkaloids, 27 organic acids, and 25 others. The characteristic fragmentation patterns of 12 representative components were summarized. As the major compounds, GC-FID quantified 6 unsaturated fatty acids and 8 saturated fatty acids in GLSP and Ganoderma sinense spore powder with little difference. Then, 7 potential p38 MAPK inhibitors were virtually screened out based on the pharmacophore modelling and molecular docking. Finally, Ganoderic acid C6, D, G, AM1, Ganoderenic acid F, Methyl lucidenate E2 were quantified in GLSP samples, and the selected 6 triterpenoids were evaluated and verified as potential inhibitors of p38 MAPK after western blotting in HepG2 cells, which could provide a theoretical basis for new therapeutic opportunities by targeting p38 MAPK signaling with few side effects. [Display omitted] •A total of 142 chemical compounds was identified in Ganoderma lucidum spore powder.•The classification and fragmentation patterns of compounds in GLSP were elucidated.•The fatty acids in GLSP, GSSP with little difference were rapidly quantified by GC-FID.•The selected triterpenes were quantified by UPLC-Orbitrap-HRMS.•Six triterpenes could be developed as new and novel p38 MAPK inhibitors.