Harriet Kim

Water extract of 1:1 mixture of Phellodendron cortex and Aralia cortex has inhibitory effects on oxidative stress in kidney of diabetic rats.

Enhanced activity of the lipid peroxidation and oxidative damages have been implicated in the pathogenesis of diabetic kidney complications. We explored to determine whether these changes in diabetic kidney could be prevented by water extract of mixture of Phellodendron cortex and Aralia cortex (P55A). Greatly elevated content of thiobarbituric acid reactive substances (TBARS) and carbonylated protein in kidneys of diabetic rats were significantly reduced by P55A treatment. In addition, abnormally low ratio of GSH/GSSG in diabetic kidneys was elevated to almost normal levels by the treatment with P55A. These results suggest that P55A extracts exert antioxidant effect by reducing lipid peroxidation and protein carbonylation as well as by elevating the ratio of GSF/GSSG in diabetic kidney.

Stimulation of ERK2 by taurine with enhanced alkaline phosphatase activity and collagen synthesis in osteoblast-like UMR-106 cells

Taurine is present in a variety of tissues and exhibits many important physiological functions in the cell. Even though its functions are well documented in many tissues, its actions on bone cells are largely unknown. Considering a recent finding that taurine is present in the bone, we wished to determine if taurine could have any effects on osteoblast cells. Taurine (10 mM) stimulated alkaline phosphatase activity as well as collagen synthesis. Taurine also stimulated tyrosine phosphorylation of a number of cellular proteins including a 42-kDa protein. The 42-kDa protein was identified as extracellular signal regulated protein kinase 2 (ERK2). A mitogen-activated protein kinase kinase (MEK) inhibitor blocked the taurine-stimulated alkaline phosphatase activity and collagen synthesis. These results suggest that taurine could regulate osteoblast metabolism via ERK2 activation.

Effect of Taurine Supplementation on the Lipid Peroxide Formation and the Activities of Glutathione-Related Enzymes in the Liver and Islet of Type I and II Diabetic Model Mice

Effects of taurine supplementation on lipid peroxide formation and the activities of glutathione (GSH) dependent enzymes in diabetic model mice were investigated. Type I diabetes mellitus was induced by injecting alloxan to ICR mice while type II diabetes mellitus was produced by high calorie diet feeding to genetically hyperglycemic KK mice. Taurine was given in drinking water at the level of 5% (w/v) for seven days. The malondialdehyde (MDA) levels of liver and the islets of type I diabetes were significantly increased compared to the control group but the levels were significantly decreased by taurine supplementation. In the type II diabetic model, the concentrations of MDA were not changed by taurine treatment. The activity of hepatic and islet GSH-peroxidase (GPX) was increased in the type I diabetic group, but in type II animals it was decreased. Hepatic GPX activity of both type I and II diabetics was not altered by taurine supplementation but was increased in the islets of the type II animals. No effect on the activity of GSH S-transferase (GST) was observed in both types of diabetes (I and II) following taurine supplementation. These results suggest that taurine supplementation protects type I diabetic mice from lipid peroxide formation.

Attenuation of Neuronal Death by NMDA and Oxygen-Glucose Deprivation in Cortical Neurons Maintained in High Glucose

Maintaining appropriate levels of glucose is essential for brain metabolism, and imbalance in glucose metabolism may result in catastrophic dysfunction of the nervous system.1,2 Hypoglycemia can produce neuronal injury through mechanisms involving activation of glutamate receptors sensitive to N-methyl-D-aspartate.3 Hyperglycemia also appears to be harmful to brain under certain pathological conditions. Systemic administration of high glucose aggravates degenerative events following hypoxic-ischemia or epilepsy.4,5 Several studies raise the possibility that increasing glucose entry to neurons may be beneficial against excitotoxicity and hypoxicischemia.6,7 We examined whether exposure to high glucose concentrations would influence the severity of excitotoxic neuronal death in vitro. Mixed cortical cell cultures, containing both neurons and glia, were prepared from brains of fetal ICR mice at 14– 15 d gestation as previously described.8 Cortical cell cultures (DIV 12) maintained in 25 mM glucose showed neuronal cell body swelling within 2 h and late death within 24 h following 10-min exposure to 100–1000 μM NMDA. The similar pattern of NMDA neurotoxicity was observed in cortical cell cultures placed in 100 mM glucose for 24 h prior to exposure to NMDA (TABLE 1). Cortical neurons maintained continuously in 100 mM glucose for 12–14 d were highly resistant to NMDA toxicity. Cortical cultures maintained in 25 mM or 100 mM glucose for 12–14 d showed the similar levels of vulnerability following 24-h exposure to 10 μM AMPA or 40 μM kainate. This suggests that prolonged exposure to high glucose protects neurons from injuries induced by NMDA, but neither AMPA nor kainate. Recognizing the property of the NMDA receptor complex as a major route of Ca2+ entry, the preferential neuroprotective effect of high glucose against NMDA likely involves detoxification of Ca2+ accumulated in neurons. To determine this possibility, we used fura-2 fluorescence microphotometry to analyze [Ca]i in cortical cell cultures. An increase in [Ca]i was detected immediately, peaked within 2 min, and was sustained over 10 min in neurons following exposure of cortical cul-

Effects of water extract of 1:1 mixture of Phellodendron cortex and Aralia cortex on polyol pathway and oxidative damage in lenses of diabetic rats.

Enhanced activity of the polyol pathway and oxidative damage have been implicated in the pathogenesis of diabetic cataract. We decided to investigate whether these changes in diabetic lenses could be prevented by the water extract of Phellodendron cortex and Aralia cortex (P55A). Aldose reductase activity was inhibited significantly by the treatment with P55A. Consequently, it caused a dramatic reduction in the high sorbitol contents observed in the lenses of diabetic rats. In addition, the greatly elevated content of thiobarbituric acid reactive substances (TBARS) and carbonylated protein in diabetic rats were reduced by P55A treatment. These results suggest that P55A extract exerts an antioxidant effect by reducing lipid peroxidation and protein carbonylation as well as having an inhibitory action against aldose reductase in the lenses of diabetic rats. Copyright

Butanol extract of 1:1 mixture of Phellodendron cortex and Aralia cortex stimulates PI3-Kinase and ERK2 with increase of glycogen levels in HepG2 cells

Extracts of Phellodendron amurense Rupr. cortex and Aralia cortex (P55A) have been used traditionally by Koreans to treat diabetes. We tested the extracts of P55A to determine if they could mimic insulin actions such as activation of ERK2, PI3‐kinase and glycogen synthesis in liver cells. The butanol extract of P55A activated ERK2 in the cytosol and nucleus of HepG2 cells; the extent of ERK2 activation was much higher in the nucleus. More strikingly, the butanol extract significantly increased the level of glycogen in HepG2 cells. Association of PI3‐kinase and IRS‐1 in the cytoplasm was also stimulated by the butanol extract of P55A. These results suggest that active component(s) of the butanol extract of P55A could regulate blood glucose levels by activating ERK2 and PI3‐kinase and by stimulation of glycogen synthesis in the liver.

Apoptotic effect of IP6 was not enhanced by co-treatment with myo-inositol in prostate carcinoma PC3 cells

Inositol hexaphosphate (IP6) is a major constituent of most cereals, legumes, nuts, oil seeds and soybean. Previous studies reported the anticancer effect of IP6 and suggested that co-treatment of IP6 with inositol may enhance anticancer effect of IP6. Although the anticancer effect of IP6 has been intensively studied, the combinational effect of IP6 and inositol and involved mechanisms are not well understood so far. In the present study, we investigated the effect of IP6 and myo-inositol (MI) on cell cycle regulation and apoptosis using PC3 prostate cancer cell lines. When cells were co-treated with IP6 and MI, the extent of cell growth inhibition was significantly increased than that by IP6 alone. To identify the effect of IP6 and MI on apoptosis, the activity of caspase-3 was measured. The caspase-3 activity was significantly increased when cells were treated with either IP6 alone or both IP6 and MI, with no significant enhancement by co-treatment. To investigate the effect of IP6 and MI of cell cycle arrest, we measured p21 mRNA expression in PC3 cells and observed significant increase in p21 mRNA by IP6. But synergistic regulation by co-treatment with IP6 and MI was not observed. In addition, there was no significant effect by co-treatment compared to IP6 treatment on the regulation of cell cycle progression although IP6 significantly changed cell cycle distribution in the presence of MI or not. Therefore, these findings support that IP6 has anticancer function by induction of apoptosis and regulation of cell cycle. However, synergistic effect by MI on cell cycle regulation and apoptosis was not observed in PC3 prostate cancer cells.