In Sil Park

Neuroprotective Effects of Dehydroglyasperin C through Activation of Heme Oxygenase-1 in Mouse Hippocampal Cells

Licorice, the root of the Glycyrrhiza species ( Glycyrrhiza uralensis Fisher), is known to have antioxidant, anti-inflammatory, antiviral, and antitumor properties. The objective of this study is to explore the neuroprotective effect of dehydroglyasperin C (DGC) against glutamate-induced oxidative stress in mouse hippocampal HT22 cells. DGC significantly reduced cytotoxicity and reactive oxygen species (ROS) generation induced by glutamate in HT22 cells, whereas DGC did not restore glutathione depletion caused by glutamate. In addition, it was further investigated whether DGC affected the expression of heme oxygenase (HO)-1, one of the major cellular antioxidant defense systems, and it was found that DGC dose-dependently increased HO-1 expression. DGC-mediated cytoprotection of HT22 neuronal cells from glutamate insult was abrogated by either HO-1 inhibitor (Tin protoporphyrin, SnPP) or AKT inhibitor (LY294002). In conclusion, the present results demonstrate for the first time that DGC protects neuronal cells against glutamate-induced oxidative injury through the induction of HO-1 expression, which is, in turn, activated maybe through Nrf2-Keap1 and PI3K/AKT signaling pathways.

Dehydroglyasperin C, a component of liquorice, attenuates proliferation and migration induced by platelet-derived growth factor in human arterial smooth muscle cells

Liquorice is one of the botanicals used frequently as a traditional medicine in the West and in the East. Platelet-derived growth factor (PDGF)-BB is involved in the development of CVD by inducing abnormal proliferation and migration of vascular smooth muscle cells. In our preliminary study, dehydroglyasperin C (DGC), an active compound of liquorice, showed strong antioxidant activity. Since phytochemicals with antioxidant activities showed beneficial effects on chronic inflammatory diseases, the present study aimed to investigate the effects of DGC on PDGF-induced proliferation and migration of human aortic smooth muscle cells (HASMC). Treatment of HASMC with DGC for 24 h significantly decreased PDGF-induced cell number and DNA synthesis in a dose-dependent manner without any cytotoxicity, as demonstrated by the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide test and thymidine incorporation. Upon cell cycle analysis, DGC blocked the PDGF-induced progression through the G0/G1 to S phase of the cell cycle, and down-regulated the expression of cyclin-dependent kinase (CDK); 2, cyclin E, CDK4 and cyclin D1. Furthermore, DGC significantly attenuated PDGF-stimulated phosphorylation of PDGF receptor-b, phospholipase C-g1, AKT and extracellular-regulated kinase 1/2, and DGC inhibited cell migration and the dissociation of actin filaments by PDGF. In a rat vascular balloon injury model, DGC suppressed an excessive reduction in luminal diameters and neointimal formation compared with the control group. These results demonstrate the mechanistic basis for the prevention of CVD and the potential therapeutic properties of DGC.

Differential abilities of Korean soybean varieties to biosynthesize glyceollins by biotic and abiotic elicitors

Glyceollins synthesized in soybeans that are exposed to biotic or abiotic stress have been reported to have health benefits. Considering that glyceollins are de novo synthesized from daidzein via several enzymatic steps and that isoflavone concentration widely varies among soybean varieties, the abilities of 60 soybean cultivars to synthesize glyceollins were compared under different elicitation conditions. Soybeans accumulated glyceollins differentially depending upon the cultivar when elicited with Aspergillus sojae. Contrary to our hypothesis that high isoflavone varieties may accumulate glyceollins more efficiently upon elicitation, glyceollin accumulation in response to fungal elicitation was not related with the concentration of either total isoflavones or daidzein in soybeans. Rather the glyceollin levels were significantly affected by soybean cultivar and most effectively increased by fungal infection. The data suggest that the selection of a strong fungal elicitor and a soybean cultivar with genotype that highly expresses the genes involved in glyceollin biosynthesis is essential for efficient glyceollin production.

Nrf2-mediated induction of phase 2 detoxifying enzymes by curled dock ( Rumex crispus L.) seed extract

Curled dock (Rumex crispus L.) is known to have several health benefits including antioxidant, antifungal, and anti-inflammatory effects. The potential to induce phase 2 detoxifying enzymes of butanol extract of curled dock (BECD) seeds was investigated. BECD increased the activity of NAD(P)H:quinone oxidoreductase and expression of phase 2 detoxifying enzymes such as heme oxygenase 1, Γ-glutamylcysteine synthetase, NAD(P)H:quinone oxidoreductase, and glutathione reductase, in both hepa1c1c7 and its mutant BPRc1 cells. The translocation of transcription factor nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) and binding to antioxidant response element (ARE) in the promoter region of phase 2 detoxifying/antioxidant enzymes were promoted by BECD in HepG2-C8 cells. Furthermore, BECD enhanced phosphorylation of Akt in hepatoma cell lines while Nrf2 activation induced by BECD was suppressed by an inhibitor of Akt. This result suggests that BECD induces phase 2 detoxifying enzymes through the Akt/Nrf2/ARE signaling pathway. BECD merits further study to be developed as detoxification agent.

Neuroprotective Effects of Dehydroglyasperin C through Increased Expression of Heme oxygenase-1 in Mouse Hippocampal Cells

. The objective of this study was to explore the neuroprotective effect of dehydroglyasperin C (DGC) againstglutamate-induced oxidative stress in the mouse hippocampal HT22 cells. DGC signiÞcantly reduced cytotoxicity and reactive oxygenspecies (ROS) generation induced by glutamate in HT22 cells, whereas DGC did not restore glutathione depletion caused by glutamate. Inaddition, we investigated further whether DGC affected the expression of heme oxygenase (HO)-1, one of major cellular antioxidantdefense systems, and found that DGC dose-dependently increased HO-1 expression. DGC-mediated cytoprotection of HT22 neuronal cellsfrom glutamate insult was abrogated by either HO-1 inhibitor (Tin protoporphyrin, SnPP) or AKT inhibitor (LY294002). In conclusion,the present results demonstrate for the Þrst time that DGC protects neuronal cells against glutamate-induced oxidative injury through theinduction of HO-1 expression which is, in turn, activated maybe through Nrf2-Keap1 and PI3K/AKT signaling pathways.