Deacetyl Ganoderic Acid F Inhibits LPS-Induced Neural Inflammation via NF-κB Pathway Both In Vitro and In Vivo

Abstract

Microglia mediated neuronal inflammation has been widely reported to be responsible for neurodegenerative disease. Deacetyl ganoderic acid F (DeGA F) is a triterpenoid isolated from Ganoderma lucidum, which is a famous edible and medicinal mushroom used for treatment of dizziness and insomnia in traditional medicine for a long time. In this study the inhibitory effects and mechanisms of DeGA F against lipopolysaccharide (LPS)-induced inflammation both in vitro and in vivo were investigated. On murine microglial cell line BV-2 cells, DeGA F treatment inhibited LPS-triggered NO production and iNOS expression and affected the secretion and mRNA levels of relative inflammatory cytokines. DeGA F inhibited LPS-induced activation of the NF-κB pathway, as evidenced by decreased phosphorylation of IKK and IκB and the nuclear translocation of P65. In vivo, DeGA F treatment effectively inhibited NO production in zebrafish embryos. Moreover, DeGA F suppressed the serum levels of pro-inflammatory cytokines, including TNF-α and IL-6 in LPS-stimulated mice model. DeGA F reduced inflammatory response by suppressing microglia and astrocytes activation and also suppressed LPS-induced NF-κB activation in mice brains. Taken together, DeGA F exhibited remarkable anti-inflammatory effects and promising therapeutic potential for neural inflammation associated diseases.

Exendin-4 improves long-term potentiation and neuronal dendritic growth in vivo and in vitro obesity condition

“…Several studies have demonstrated that insulin resistance by IRS-1 and IRS-2 dysregulation in the brain causes onset of neurodegenerative disease and results in cognitive decline 54 , 56 . Serine phosphorylation of IRS-1 elevates amyloid beta accumulation and exacerbates memory deficit in AD brain 57 . In addition, insulin receptor knockout mice showed abnormal synaptic transmission and reduction of AKT signaling activation 58 .…”

Ganoderic Acids Prevent Renal Ischemia Reperfusion Injury by Inhibiting Inflammation and Apoptosis

“…Two major active components are responsible: G. lucidum polysaccharides and G. lucidum triterpenoids (GTs) [ 15 ]. As one of the most abundant GTs, ganoderic acids (GAs) have anti-inflammatory, anti-oxidative stress, anti-tumor and anti-apoptotic effects [ 16 , 17 , 18 , 19 ]. It has been reported that Ganoderic Acid F, one component of GAs, can suppress LPS-induced the activation of NF-kB pathway and inhibit LPS-triggered iNOS expression and the production and secretion of relative inflammatory cytokines in mice [ 16 ].…”

“…As one of the most abundant GTs, ganoderic acids (GAs) have anti-inflammatory, anti-oxidative stress, anti-tumor and anti-apoptotic effects [ 16 , 17 , 18 , 19 ]. It has been reported that Ganoderic Acid F, one component of GAs, can suppress LPS-induced the activation of NF-kB pathway and inhibit LPS-triggered iNOS expression and the production and secretion of relative inflammatory cytokines in mice [ 16 ]. Therefore, we hypothesize that GAs can alleviate RIRI via inhibiting inflammatory response and cell apoptosis.…”

Involvement of NFƙB and MAPK signaling pathways in the preventive effects of Ganoderma lucidum on the inflammation of BV-2 microglial cells induced by LPS

“…DeGA F inhibited mRNA expression of TNF-α , IL-6 , and IL-1β . Also, the pretreatment with DeGA F inhibited the protein expression of Akt, IKKα/β, and IκBα (which participate in the NFƙB activation), compared to the LPS-stimulated cells ( Sheng et al, 2019 ). Polysaccharides from G. lucidum have also been shown to inhibit LPS- and Aβ-induced pro-inflammatory levels of IL-1β, IL-6, and iNOS, and induce the expression of the anti-inflammatory cytokine TGFβ ( Cai et al, 2017 ).…”