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.
Dangguijagyagsan (DJS), a traditional herbal prescription, has long been used to treat menopause-related symptoms. We identified the cardioprotective effects of an aqueous extract of DJS using an ovariectomized (OVX) and ferric chloride- (FeCl-) induced carotid thrombosis rat model. Female Sprague-Dawley (SD) rats were ovariectomized or Sham-operated (Sham-control). The ovariectomized rats were divided into three groups: OVX with saline (OVX-control), aspirin 30 mg/kg/day (OVX-ASA), and DJS 100 mg/kg/day (OVX-DJS). The treatments were administered for 5 weeks. Then, blood samples were collected to analyze the serum lipid levels and platelet aggregation. The topical application of 40% FeCl3 induced intravascular thrombosis, which was used to test thrombotic occlusion and for histological examination. Body weight and the levels of total cholesterol (TC), triglyceride (TG), and LDL-cholesterol (LDL-C) increased in the OVX rats. These effects were reduced by ASA and DJS treatment. In addition, ASA and DJS treatment significantly inhibited platelet aggregation. These treatments also increased time to occlusion and decreased both thrombus size and the presence of collagen fibers in surrounding vessel walls compared with the Sham-control and OVX-control groups. These results suggest that DJS has beneficial effects in terms of preventing cardiovascular disease in menopausal woman because it can reduce the serum lipid levels and improve blood flow by inhibiting platelet aggregation and thrombus formation.
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 G 0 /G 1 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.Key words: Dehydroglyasperin C: Vascular smooth muscle cells: Platelet-derived growth factor-BB: Platelet-derived growth factor signalling pathway: Proliferation: Migration Accumulation of vascular smooth muscle cells (VSMC) is a key event in the formation and development of lesions in atherosclerosis. The excessive accumulation of VSMC is due to a combination of directed migration from the media into the intima of the artery accompanied by proliferation and possibly decreased apoptosis. The proliferation and migration of VSMC are associated with vascular change through intimal lesion formation, and these can be induced by growth factors, such as PDGF. PDGF is expressed in various vascular cells such as VSMC, endothelial cells, platelets and macrophages, and platelet-derived growth factor-BB (PDGF-BB) is a more potent inducer of VSMC proliferation and migration than PDGF-AA and -AB (1 -4) .However, the mechanisms related to the PDGF-stimulated proliferation and migration of smooth muscle cells have not yet been fully elucidated. Several studies have shown that PDGF disrupts actin filament assembly and increases the expression of the PDGF-b receptor (PDGFR-b) in injured carotid arteries (5) . PDGF-BB developed intimal thickening and VSMC migration from the media to the intima in a rat model of angioplasty (6) . Consistent with the results, it has been shown that a selective PDGF...
Glyceollins synthesized in soybeans that are exposed to biotic or abiotic stress have been reported to have health benefits. Considering that glyceollins are 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. 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.
BackgroundThe incidence of breast cancer has been gradually increasing in Korea. Recently, the elevated level of serum gamma-glutamyltransferase (GGT) has emerged to be associated with the development and progression of some malignancies. This study aimed to determine the effect of serum GGT levels on the risk of developing breast cancer in Korean women.MethodsWe used National Health Insurance Service Health Checkup data to examine the association between serum GGT levels and breast cancer development in Korean women. Women aged 40 years or older who participated in the Korean National Health Screening Examination between January 2009 and December 2009 and who did not develop any cancer within 1-year post examination were included in this analysis (n = 3,109,506). Cox proportional hazard regression analysis was conducted to calculate hazard ratios (HRs) with 95% confidence intervals (CIs).ResultsOverall, an elevated serum GGT level was associated with the increased risk of developing breast cancer; compared to the Q1 group, the Q4 group showed a significantly increased breast cancer risk (HR: 1.120,95% CI: 1.08–1.162). Such a relationship was stronger in post-menopausal women than pre-menopausal women (HR: 1.173, 95% CI: 1.107–1.243; HR: 1.070, 95% CI:1.019–1.124). Women with a high GGT level (Q4) were also at an increased risk of developing carcinoma in situ (CIS) (HR: 1.114, 95% CI: 1.04–1.192). In post-menopausal women, the Q4 group also exhibited higher CIS risk (HR: 1.266, 95% CI: 1.132–1.416). However, no significant difference in the risk of developing CIS was observed between the Q1 and Q4 groups in pre-menopausal women. Further analysis revealed that obese, post-menopausal women with a high GGT level (Q4) were associated with an increased risk of developing breast cancer (HR: 1.214, 95% CI: 1.125–1.31) and CIS (HR: 1.348, 95% CI: 1.159–1.569).ConclusionsOur study results demonstrate that increased serum GGT level is a risk factor for developing breast cancer. The post-menopausal women group with obesity and elevated serum GGT level showed the highest incidence of breast cancer. Thus, serum GGT concentration could be a novel and potential risk factor for breast cancer. Further validation in different ethnic groups would be warranted.
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