Jehun Choi

Modulation of NF-κB and FOXOs by baicalein attenuates the radiation-induced inflammatory process in mouse kidney

Abstract The bioactive flavonoid baicalein has been shown to have radioprotective activity, although the molecular mechanism is poorly understood in vivo. C57BL/6 mice were irradiated with X-rays (15 Gy) with and without baicalein treatment (5 mg/kg/day). Irradiation groups showed an increase of NF-κB-mediated inflammatory factors with oxidative damage and showed inactivation of FOXO and its target genes, catalase and SOD. However, baicalein suppressed radiation-induced inflammatory response by negatively regulating NF-κB and up-regulating FOXO activation and catalase and SOD activities. Furthermore, baicalein inhibited radiation-induced phosphorylation of MAPKs and Akt, which are the upstream kinases of NF-κB and FOXOs. Based on these findings, it is concluded that baicalein has a radioprotective effect against NF-κB-mediated inflammatory response through MAPKs and the Akt pathway, which is accompanied by the protective effects on FOXO and its target genes, catalase and SOD. Thus, these findings provide new insights into the molecular mechanism underlying the radioprotective role of baicalein in mice.

The Anti-Inflammatory Action of Fermented Soybean Products in Kidney of High-Fat-Fed Rats

Soybean has many compounds with a variety of biological properties that potentially benefit human health; among them, isoflavones have inhibitory effects on lipid oxidation in adipose tissue. In this study, we examined two Korean traditional fermented soybean products--doenjang (DNJ) and cheonggukjang (CGJ)--for their ability to suppress redox-sensitive nuclear factor κB (NF-κB) activation in the kidney of rats fed a high-fat diet. Sprague-Dawley rats, 4 weeks old, were fed soybean, DNJ, or CGJ (1 g/kg/day) with a 20% fat diet for 6 weeks. Body weight and food intake were carefully monitored. NF-κB-related activities of genes for inflammatory proteins, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and vascular cell adhesion molecule-1 (VCAM-1), were determined. The soybean products exhibited antioxidative action by maintaining redox regulation, suppressing NF-κB activation, and modulating the expression of genes for NF-κB-induced inflammatory proteins such as COX-2, iNOS, and VCAM-1. Based on these results, we conclude that Korean traditional soybean fermented products, especially CGJ, suppress the generation of reactive species, NF-κB activity, and NF-κB-related inflammatory genes.

5-Hydroxytrytophan inhibits tert-butylhydroperoxide (t-BHP)-induced oxidative damage via the suppression of reactive species (RS) and nuclear factor-κB (NF-κB) activation on human fibroblast.

5-Hydroxytryptophan (5HTP), an analogue of tryptophan, is a precursor of serotonin that also has effective antioxidative and anti-apoptotic properties (1) . However, the cellular mechanisms underlying these properties of 5HTP have not been explored. In this study, we tested the hypothesis that 5HTP exerts its antioxidative action against oxidative stress and inflammation by suppressing the activation of the key pro-inflammatory transcriptional pathways, p38 mitogen-activated protein kinase (p38MAPK) and nuclear factor-kappaB (NF-kappaB). The study was carried out using human fibroblast cells that were challenged by tert-butylhydroperoxide (t-BHP)-induced oxidative damage. Results show that 5HTP significantly reduced t-BHP-induced oxidative damage in human fibroblast cells, as determined by cell cytotoxicity, intracellular reactive species (RS) and peroxynitrite (ONOO(-)) generation, and inducible nitric oxide synthase expression. Moreover, 5HTP protected human fibroblast cells against t-BHP-induced oxidative DNA damage, as determined by 4,6-diamidino-2-phenlylindole (DAPI) staining. Pretreatment of human fibroblast cells with 5HTP also dose-dependently inhibited glutathione (GSH) depletion, indicating that it protects cells against t-BHP-induced oxidative damage. Western blot analysis revealed that 5HTP also markedly increased Bcl-2 expression and suppressed both p38MAPK and NF-kappaB activation in the t-BHP-treated human fibroblast cells. When these results are taken together, they strongly indicate that 5HTP has beneficial and protective effects against t-BHP-induced cell death in vitro, as demonstrated by its antioxidative and anti-inflammatory actions. Data further showed that the protective mechanisms underlying the actions of 5HTP against oxidative stress-induced damage are associated with RS/ONOO(-) scavenging and the inhibition of lipid peroxidation and GSH depletion.

A newly synthesized, potent tyrosinase inhibitor: 5-(6-Hydroxy-2-naphthyl)-1,2,3-benzenetriol

In searching for new agents with a depigmenting effect, we synthesized a derivative of resveratrol, 5-(6-hydroxy-2-naphthyl)-1,2,3-benzenetriol (5HNB) with a potent tyrosinase inhibitory activity. 5HNB inhibited mushroom tyrosinase with an IC(50) value of 2.95 microM, which is more potent than the well-known anti-tyrosinase activity of kojic acid (IC(50)=38.24). The results of the enzymatic inhibition kinetics by Lineweaver-Burk analysis indicated 5HNB inhibits tyrosinase non-competitively when L-tyrosine was used as the substrate. Based on the strong inhibitory action of 5HNB, it is expected that 5HNB can suppress melanin production in which tyrosinase plays the essential role. Our expectation was confirmed by the experimentations with B16 melanoma cells in which 5HNB inhibited melanin production. We propose that 5HNB might have skin-whitening effects as well as therapeutic potential for treating skin pigmentation disorders.

Molecular basis for age-related changes in ileum: Involvement of Bax/caspase-dependent mitochondrial apoptotic signaling

Previous studies indicate that in the elderly, a morphological change in the small intestine is accompanied by apoptosis. However, currently little information is available on the molecular events leading up to the apoptotic process in aged ileum. Our current study assessed mitochondrial apoptotic signaling along with key factors known to be involved in mitochondrial permeabilization in rat ileum. Experimentations were carried out utilizing Sprague-Dawley rats at 6 and 24 months of age. The histological analysis showed a significant loss in thickness of the intestinal mucosa during aging, which was accompanied by higher reactive species. Molecular analysis revealed the mitochondrial translocation of Bax showed a significant increase with aging. However, the expression of cyclophilin D, adenine nucleotide translocator, and the voltage-dependent anion channel that regulates the mitochondria permeability transition pore decreased or remained unchanged. Furthermore, the expression of caspase 3 was enhanced in aged ileum with increased DNA fragmentation, while nuclear translocation of apoptosis-inducing factor and endonuclease G were decreased with aging. In conclusion, our findings indicate that the mitochondrial translocation of Bax by increased oxidative stress may result in cell death through caspase-dependent apoptosis in aged ileum, thereby leading to a decrease in intestinal mucosal thickness during aging.

Effects of daidzein on alveolar bone loss and internal microstructures of bone in a rat model of experimental periodontitis: a study using micro-computed tomography

BACKGROUND AND OBJECTIVE Daidzein is an isoflavone abundant in soybeans, kudzu root and red clover, which have been widely studied for its therapeutic potential. The present study was designed to evaluate the effects of daidzein on alveolar bone loss and internal microstructures of bone in a rat model of experimental periodontitis by assessing morphological data obtained from micro-computed tomography (micro-CT). MATERIAL AND METHODS Twenty-four male Sprague-Dawley rats were randomly assigned to the following three groups comprising eight animals each: the nonligation (NL) group; the ligation (L) group; and the ligation+daidzein (LD) group. To induce periodontitis, a 4-0 braided silk ligature was tied around the cervical area of the lower-right first molars of rats in groups L and LD. Rats in the LD group were given daily doses of daidzein (10 mg/kg of body weight) by intraperitoneal injection immediately after ligature placement. Two weeks after the placement of ligatures, mandibular block biopsies were scanned using a micro-CT system. RESULTS Daily administration of daidzein strongly suppressed the ligature-induced loss of alveolar bone height. In addition, when rats were treated with daidzein, the ligature-induced decrease in the bone volume fraction was significantly recovered. Furthermore, daidzein significantly reversed ligature-induced deteriorations in the microarchitecture parameters of trabecular bone, such as trabecular thickness, bone mineral density, trabecular separation and structure model index. CONCLUSION The study presented here demonstrates, for the first time, that daidzein effectively reduces alveolar bone destruction resulting from experimental periodontitis in rats. Further studies are necessary for the translation of this compound clinically to improve the outcomes of patients diagnosed with periodontitis.