Ganoderterpene A, a New Triterpenoid from Ganoderma lucidum , Attenuates LPS-Induced Inflammation and Apoptosis via Suppressing MAPK and TLR-4/NF-κB Pathways in BV-2 Cells.

An investigation of the fruiting bodies of edible mushroom Ganoderma lucidum produced 13 steroids, containing one new lanostane-type triterpene compound, named ganoderterpene A ( 1 ). Nuclear magnetic resonance and high-resolution electrospray ionization mass spectrometry data were used to deduce these structures. All the isolates were evaluated for their ability to suppress NO generation in BV-2 microglial cells treated with lipopolysaccharide (LPS) and exhibited moderate to strong inhibition effects, with IC ₅₀ values in the range 7.15-36.88 μ M. Among the tested compounds, compound 1 exhibited the most marked activity with an IC ₅₀ value of 7.15 μ M, and the structure-activity relationships were studied. This study showed that compound 1 significantly suppressed the activation of MAPK and TLR-4/NF-κB signaling pathways, as evidenced by an immunofluorescence assay and a molecular docking experiment. Furthermore, compound 1 effectively improved the LPS-induced mitochondrial membrane potential and apoptosis. These findings suggest that ganoderterpene A could exert protective effects in microglial cells from apoptosis by restraining the inflammatory response. Hence, G. lucidum could be used as a novel preventative agent for neurodegenerative disorders.