Radicicol Inhibits iNOS Expression in Cytokine-Stimulated Pancreatic Beta Cells

Here, we show that radicicol, a fungal antibiotic, resulted in marked inhibition of inducible nitric oxide synthase (iNOS) transcription by the pancreatic beta cell line MIN6N8a in response to cytokine mixture (CM: TNF-alpha, IFN-gamma, and IL-1beta). Treatment of MIN6N8a cells with radicicol inhibited CM-stimulated activation of NF-kappaB/Rel, which plays a critical role in iNOS transcription, in a dose-related manner. Nitrite production in the presence of PD98059, a specific inhibitor of the extracellular signal-regulated protein kinase-1 and 2 (ERK1/2) pathway, was dramatically diminished, suggesting that the ERK1/2 pathway is involved in CM-induced iNOS expression. In contrast, SB203580, a specific inhibitor of p38, had no effect on nitrite generation. Collectively, this series of experiments indicates that radicicol inhibits iNOS gene expression by blocking ERK1/2 signaling. Due to the critical role that NO release plays in mediating destruction of pancreatic beta cells, the inhibitory effects of radicicol on iNOS expression suggest that radicicol may represent a useful anti-diabetic activity.

Synergistic Induction of iNOS by IFN-gamma and Glycoprotein Isolated from Dioscorea batatas

Dioscorea species continue to be used in traditional Chinese medicine, and represent a major source of steroid precursors for conventional medicine. In the previous study, We isolated glycoprotein (GDB) from Dioscorea batatas, characterized, and demonstrated immunostimulating activity in C57BL/6 mice. The aim of this study was to investigate the mechanism whereby GDB activates macrophages. Macrophages activation by GDB was investigated by analyzing the effects of GDB on nitric oxide (NO) production, iNOS expression, mitogen activated protein kinase (MAPK) phosphorylation, and transcription factor activation. In the presence of IFN-gamma, GDB strongly stimulated macrophages to express iNOS and produce NO. Furthermore, the activation of p38 was synergistically induced by GDB plus IFN-gamma , but SB203580 (a p38 inhibitor) inhibited GDB plus IFN-gamma-induced p38 activation. This study indicates that GDB is an important activator of macrophages. Furthermore, due to the critical role that macrophage activation plays in innate immune response, the activation effects of GDB on macrophages suggest that GDB may be a useful immunopotentiating agent.

Magnolol Inhibits LPS-induced NF-kappaB/Rel Activation by Blocking p38 Kinase in Murine Macrophages

This study demonstrates the ability of magnolol, a hydroxylated biphenyl compound isolated from Magnolia officinalis, to inhibit LPS-induced expression of iNOS gene and activation of NF-kappaB/Rel in RAW 264.7 cells. Immunohisto-chemical staining of iNOS and Western blot analysis showed magnolol to inhibit iNOS gene expression. Reporter gene assay and electrophoretic mobility shift assay showed that magnolol inhibited NF-kappaB/Rel transcriptional activation and DNA binding, respectively. Since p38 is important in the regulation of iNOS gene expression, we investigated the possibility that magnolol to target p38 for its anti-inflammatory effects. A molecular modeling study proposed a binding position for magnolol that targets the ATP binding site of p38 kinase (3GC7). Direct interaction of magnolol and p38 was further confirmed by pull down assay using magnolol conjugated to Sepharose 4B beads. The specific p38 inhibitor SB203580 abrogated the LPS-induced NF-kappaB/Rel activation, whereas the selective MEK-1 inhibitor PD98059 did not affect the NF-kappaB/Rel. Collectively, the results of the series of experiments indicate that magnolol inhibits iNOS gene expression by blocking NF-kappaB/Rel and p38 kinase signaling.

A Study of Predicting Postpartum Depression and the Recovery Factor from Prepartum Depression / 대한주산의학회잡지

OBJECTIVE: To discover the risk factor of postpartum depression and whether this is different from the induced factor of prepartum depression and to clarify what is the recovery factor from prepartum depression. METHODS: In the first test stage, 310 pregnant women were examined and with their postpartum follow-up survey, materials from 85 people in total were retrieved. In order to predict the postpartum depression and find out the recovery factor from prepartum depression, longitudinal study was carried out. For the statistical analysis hierarchical regression analysis and MANOVA were used. RESULTS: Postpartum depression (Beck Depression Inventory; BDI score of 16 or greater) was prevalent amongst 22.4% of pregnant women and prepartum depression was experienced by 10.5% in pregnant women. There were no significant on psychological variable factor of prepartum and postpartum depression. Only preatum depression redicted 33% for postaprtum depression. In the case of depressed during pregnancy but not depressed after pregnancy, recovery factor is related to increase in self-esteem, husband support and improvement in marital satisfaction. Postpartum depression showed twice higher depression ration than prepartum depression and it was serious in terms of degree of depression. CONCLUSION: Postpartum depression is related with lack of husband support that is recovery factor from prepartum depression. Also, unstable attachment is vulnerable to depression but even people with unstable attachment can be recovered from depression with better marriage relationship. Even people without unstable attachment if husband support is reduced then it is suggested that can be subject to vulnerability in depression.