Anti-inflammatory effects of glaucocalyxin B in microglia cells

Abstract

Over-activated microglia is involved in various kinds of neurodegenerative process including Parkinson, Alzheimer and HIV dementia. Suppression of microglial over activation has emerged as a novel strategy for treatment of neuroinflammation-based neurodegeneration. In the current study, anti-inflammatory and neuroprotective effects of the ent-kauranoid diterpenoids, which were isolated from the aerial parts of Rabdosia japonica (Burm. f.) var. glaucocalyx (Maxim.) Hara, were investigated in cultured microglia cells. Glaucocalyxin B (GLB), one of five ent-kauranoid diterpenoids, significantly decreased the generation of nitric oxide (NO), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) in the lipopolysaccharide (LPS)-activated microglia cells. In addition, GLB inhibited activation of nuclear factor-κB (NF-κB), p38 mitogen-activated protein kinase (MAPK) and generation of reactive oxygen species (ROS) in LPS-activated microglia cells. Furthermore, GLB strongly induced the expression of heme oxygenase (HO)-1 in BV-2 microglia cells. Finally, GLB exhibited neuroprotective effect by preventing over-activated microglia induced neurotoxicity in a microglia/neuron co-culture model. Taken together, the present study demonstrated that the GLB possesses anti-nueroinflammatory activity, and might serve as a potential therapeutic agent for treating neuroinflammatory diseases.

Glaucocalyxin B protects against oxygen‐glucose‐deprivation/reperfusion‐induced neuronal injury in PC‐12 cells

“…[10][11][12] Glaucocalyxin is an ent-kaurane diterpenoid isolated from R. japonica. 15 However, the effect of GLB on oxygen-glucose-deprivation/reperfusion (OGD/R)-induced cell injury in PC-12 cells has not been explored. Pan et al 14 reported that GLB inhibited the proliferation of human cervical cancer cells in vitro through the induction of apoptosis and autophagy.…”

“…In addition, one study reported that GLB significantly suppressed the production of nitric oxide, tumor necrosis factor, interleukin, and expression of cyclooxygenase and inducible nitric oxide synthase in the lipopolysaccharide (LPS)-activated microglia cells. 15 However, the effect of GLB on oxygen-glucose-deprivation/reperfusion (OGD/R)-induced cell injury in PC-12 cells has not been explored. Our results indicated that GLB protects against OGD/R-induced neuronal injury in PC-12 cells by activating the Akt/mTOR signaling pathway.…”

Glaucocalyxin B Alleviates Lipopolysaccharide-Induced Parkinson’s Disease by Inhibiting TLR/NF-κB and Activating Nrf2/HO-1 Pathway

“…Glaucocalyxin B (GLB) is an ent -kauranoid diterpenoid isolated from a perennial herb, Rabdosia japonica . GLB has been reported to suppress lipopolysaccharide (LPS)-induced inflammation in microglia [11]. GLB inhibits the proliferation of human cervical cancer cells through inducing apoptosis and autophagy, which is mediated by the PI3K/Akt signaling pathway [12].…”

Reducing the Search Space in Literature-Based Discovery by Exploring Outlier Documents: a Case Study in Finding Links Between Gut Microbiome and Alzheimer’s Disease

“…In particular, in the gut, iNOS induces intestinal barrier damage [31], and in the brain causes nitrosylation of proteins and cell death with neurological consequences like dementia, Alzheimer or Parkinson diseases [32,33]. Even though NO is locally produced, its effects can diffuse systemically, thus influencing the progression of the disease [34][35][36] [ [34][35][36]. Bioactive nutrients possibly modulate individual microbiome responses limiting inflammation and free radical synthesis, including NO [37].…”

“…Among them, in our first experiment, we identified and decided to focus on the term "nitric oxide synthase" [27] as a promising novel bridging term. From the set of articles that were used as input to CrossBee the expert carefully reviewed the four articles containing this term; three from the "Alzheimer" domain [34][35][36] [ [34][35][36] and one from the "gut microbiota" domain [30]. In addition, the combined query "Alzheimer gut nitric oxide" in PubMed revealed that there are no articles that correspond to this query, which is especially interesting, indicating that this connection was not previously explored in the available literature.…”