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

Abstract

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 IC50 values in the range 7.15–36.88 μM. Among the tested compounds, compound 1 exhibited the most marked activity with an IC50 value of 7.15 μM, 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.

(±)-Spiroganoapplanin A, a complex polycyclic meroterpenoid dimer from Ganoderma applanatum displaying potential against Alzheimer's disease

“…651.1473), which indicated 21 degrees of unsaturation. However, the 13 C NMR spectrum only showed 28 carbon resonances, which were attributed to two methoxyls, one oxygenated methylene, one sp 3 methine, one oxygenated methine, ten sp 2 methines, one oxygenated quaternary carbon, eight sp 2 quaternary carbons, two aldehyde groups, and two ester carbonyls. Two sets of 1,2,4-trisubstituted phenyl signals {δ H 6.80 (d, J = 2.7 Hz, H-3a), δ H 7.14 (dd, J = 8.9 and 2.7 Hz, H-5a), δ H 6.92 (d, J = 8.9 Hz, H-6a); δ H 6.30 (d, J = 2.9 Hz, H-3b), δ H 6.75 (dd, J = 9.0 and 2.9 Hz, H-5b), δ H 6.84 (d, J = 9.0 Hz, H-6b)} with ABX systems were observed in the 1 H NMR spectroscopic data (298 K) (Table S1 Furthermore, in the HMBC spectrum (298 K) (Fig.…”

“…To certify this hypothesis, a variable-temperature NMR experiment was carried out. The 1 H and 13 C NMR signals in the red part (Fig. 2A) appeared as the temperature was lowered (Fig.…”

“…12 The ancient Chinese agronomy book Shennong's Herbal Classic and Compendium of Materia Medica described the medical benefits of Ganoderma such as prolonging life-span, keeping health, improving intelligence and memory. 13 Modern pharmacological research studies have also provided evidence of the possible therapeutic effects of Ganoderma and its extracts on AD through inhibiting inflammation, resisting oxidation pressure and reducing the aggregation of Aβ. [14][15][16][17][18] Furthermore, Ganoderma meroterpenoids (GMs) have been found to possess neuroprotective potential in different in vitro models.…”

Ganoderma Lucidum Triterpenoids Improve Maternal Separation-Induced Anxiety- and Depression-like Behaviors in Mice by Mitigating Inflammation in the Periphery and Brain

“…Deacetyl ganoderic acid F, another kind of triterpene obtained from G. lucidum , was found to suppress LPS-induced neural inflammation in vivo and significantly reduce the expression of inflammatory factors in the peripheral serum of mice [ 25 ]. A new triterpenoid from G. lucidum , named Ganoderterpene A, was evidenced to protect microglia from apoptosis by restraining the inflammatory response [ 12 ]. In our study, GLTs were systemically administered, which is consistent with the clinical medication practices of traditional Chinese medicine [ 10 , 62 ].…”

“…As a medicinal mushroom, Ganoderma lucidum ( G. lucidum ) plays a significant role in disease treatments and longevity promotion in several countries, especially in the East Asian [ 10 ]. As a category of the main bioactive and medicative components in G. lucidum , Ganoderma lucidum triterpenoids (GLTs) are documented to perform various pharmacological actions such as anticancer [ 11 ], anti-inflammation [ 12 , 13 ], anti-atherosclerosis [ 14 ], anti-hyperlipidemia [ 15 ], antioxidants [ 16 , 17 ], antivirus [ 18 ], hepatoprotection [ 19 ], retardation renal cyst [ 20 ], renal fibrosis development, and protection of renal ischemia-reperfusion injury [ 21 ]. Moreover, recent studies evidence that GLTs can also exert pharmacological effects on the nervous system, alleviating neuronal apoptosis [ 22 ] and neuroinflammation [ 23 ] in Alzheimer’s disease mice.…”