A series of 6-hydroxy-7-methoxy-4-oxo-4H-chromene-2-carboxylic acid N-alkyl amides (3a-g) were synthesized and their antioxidant activities were evaluated using rat brain homogenates.

In this study, a newly-synthesized metalloporphyrin, Gd-chlorin (PB Chlorin), was investigated by using a simple tissue phantom to test its efficacy as an MRI contrast agent. This study demonstrated the potential activity of Gd-chlorin as not only a MRI contrast agent, but also as a PDT photosensitizer by using a simple tissue phantom and conducting a very brief MRI experiment.

Twigs from llex macropoda were extracted with MeOH, and the concentrated extracts were partitioned with $CH_2Cl_2$, EtOAc, n-BuOH, and $H_2O$. Repeated column chromatography of the $CH_2Cl_2$ fraction ultimately resulted in the isolation of two compounds, via activity-guided fractionation, using ACAT inhibitory activity measurements. According to the physico-chemical data, the chemical structures of these isolated compounds were identified as lupeol (1) and betulin (2). Compounds 1 and 2 were shown to inhibit the activity of hACAT-1 and hACAT-2 in a dose-dependent manner, and compounds 1 and 2 inhibited hACAT-1 with $IC_{50}$ values of 48 and $83{\mu}M$, respectively.

Slavins A (1) and B (2), the new amyrin type triterpenes, have been isolated from the chloroform soluble fraction of Salvia santolinifolia and assigned structures on the basis of spectral studies including 2D NMR. Both the compounds displayed inhibitory potential against the enzyme butyrylcholinesterase.

From the leaves of Goniothalamus tenuifolius, a new natural product namely 3'-hydroxy-3,5,7,4'-tetramethoxyflavone (1) was isolated, along with seven other known compounds (2-8). Each of these isolates was evaluated for free radical scavenging activity on the DPPH decoloration test. The data obtained in this study suggested that the ortho 3',4'-diphenolic structure was essential for the activity of these flavonol derivatives.

The chromatographic separation of the MeOH extract of the roots of Ainsliaea acerifolia (Compositae) led to the isolation of six known terpenes and two known lignans. Their structures were identified by spectroscopic methods as mokko lactone (1), betulonic acid (2), betulinic acid (3), zaluzanin C (4), $1{\beta}-hydroperoxygermacra-4(15)$, 5, 10(14)-triene (5), pluviatilol (6), (+)-syringaresinol (7), and glucozaluzanin C (8). Compounds $1{\sim}4$ and 8 showed non-specific significant cytotoxicity against five human tumor cell lines with $ED_{50}$ values ranging from $0.36{\sim}5.54{\mu}g/mL$.

We investigated the effect of protein extract of Asterina pectinifera on the activity of 4 enzymes that may playa role in adenocarcinoma of the colon: quinone reductase (QR), glutathione Stransferase (GST), ornithine decarboxylase (ODC), and cyclooxygenase (COX)-2. QR and GST activity increased in HT-29 human colon adenocarcinoma cells increased that had been exposed to 4 concentrations of the protein extract (80, 160, 200, and $240{\mu}g/mL$). Additionally, 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ODC activity decreased significantly in cells exposed to the extract in concentrations of $160{\mu}g/mL$ (p<0.05), $200{\mu}g/mL$ (p<0.005), and $240{\mu}g/mL$ (p<0.005). TPA-induced COX-2 activity also decreased in cells exposed to extract concentrations of 10, 20, 40, and $60{\mu}g/mL$. COX-2 expression was also inhibited in cells exposed to this extract. These results suggest that this protein extract of A pectinifera has chemopreventive activity in HT-29 human colon adenocarcinoma cells, and therefore, may have the potential to function as a chemopreventive agent in human colorectal cancer.

The present study was undertaken to test the hypothesis that dietary antioxidants protect DNA damage induced by peroxynitrite, a potent physiological inorganic toxin. The present study showed that dietary antioxidants such as (-)-epigallocatechin gallate, quercerin, rutin, resveratrol, and ursolic acid inhibit single strand breaks in supercoiled plasmid DNA induced by 3-morpholinosydnomine N-ethylcarbamide (SIN-1), a generator of peroxynitrite through the reaction between nitric oxide and superoxide anion. The formation of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) in calf thymus DNA by SIN-1 was also inhibited by dietary antioxidants. When U937 cells were incubated with 1 mM SIN-1 bolus, a significant increase of 8-OH-dG level was observed. However, oxidative DNA damage was significantly lower in the cells pre-treated with dietary antioxidants when cells were exposed to SIN-1.

Erythropoietin (EPO), a hematopoietic factor, is required for normal erythrocyte developments, but it has been demonstrated to have many other functions, and its receptor is localized in other tissues. In the present study, we investigated whether EPO can promote other cell proliferation and possible molecular mechanisms. EPO restored the inhibition of the RAW264.7 and PC12 cell growth by fetal bovine serum (FBS) withdrawal in a dose dependent manner, but not that of other cell types tested. The restoring effect of EPO was completed when the RAW264.7 cells were cultured in the medium containing as low as 3% of FBS, and 10 U/mL EPO could replace FBS. The restoring effect of EPO in the RAW264.7 cells was associated with the increased of c-Fos and c-Jun expression as well as AP-1 activation. These data demonstrate that EPO can stimulate RAW264. 7 cell as well as PC12 cell growth even when the cells were cultured without FBS or in the presence of small amounts of FBS in the medium, and this stimulating effect is associated with the activation of AP-1 transcription factor.

We employed human SK-MEL-28 cells as a model system to identify cellular proteins that accompany N-(4-methyl)phenyl-O-(4-methoxy)phenyl-thionocarbamate (MMTC)-induced apoptosis based on a proteomic approach. Cell viability tests revealed that SK-MEL-28 skin cancer cells underwent more cell death than normal HaCaT cells in a dose-dependent manner after treatment with MMTC. Two-dimensional electrophoresis in conjunction with matrixassisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry analysis or computer matching with a protein database further revealed that the MMTC-induced apoptosis is accompanied by increased levels of caspase-1, checkpoint suppressor-1, caspase-4, NF-kB inhibitor, AP-2, c-Jun-N-terminal kinase, melanoma inhibitor, granzyme K, G1/S specific cyclin D3, cystein rich protein, Ras-related protein Rab-37 or Ras-related protein Rab-13, and reduced levels of EMS (oncogene), ATP synthase, tyrosine-phosphatase, Cdc25c, 14-3-3 protein or specific structure of nuclear receptor. The migration suppressing effect of MMTC on SK-MEL-28 cell was tested. MMTC suppressed the metastasis of SK-MEL-8 cells. It was also identified that MMTC had little angiogenic effect because it did not suppress the proliferation of HUVEC cell line. These results suggest that MMTC is a novel chemotherapeutic and metastatic agents against the SK-MEL-28 human melanoma cell line.

The oral administration of extracts of young radishes cultivated with sulfur after intravenous tumor cell injection achieved a marked reduction of pulmonary colonization in mice. Treatment of the mice with extracts of young radish cultivated with sulfur did not show any increase in the number of CD8+ or NK T cells in the spleen, indicating no influence on host immunity. Sulforaphane, which could be a candidate for an active compound from young radishes cultivated with sulfur, inhibited cell growth of B16-F10 melanoma cells. In addition, extracts of the young radish cultivated with sulfur-fed group showed enhanced quinine reductase (QR) activities in the liver and lung and a slight increase of glutathione S-transferase (GST) activity in the liver. These results suggested that the administration of extracts of young radishes cultivated with sulfur suppressed pulmonary tumorigenesis, possibly due to increased activity of detoxification enzymes in the liver and lung, and partly due to cell cytotoxicity.

Angiotensin converting enzyme (ACE) inhibitors have cardioprotective effects in different species including human. This cardioprotective effect is mainly due to the inhibition of bradykinin (BK) degradation rather than inhibition of the conversion of angiotensin I to angiotensir. II. Bradykinin, a nonapeptide, has been considered to be the potential target for various enzymes including ACE, neutral endopeptidase 24.11, carboxypeptidase M, carboxypeptidase N, proline aminopeptidase, endopeptidase 24.15, and meprin. In the present study, the coronary vascular beds of Sprague Dawley rat isolated hearts were perfused (single passage) with Krebs solution alone or with different concentrations of BK i.e. $2.75{\times}10^{-10},\;10^{-7},\;10^{-6}\;and\;10^{-5}M$ solution. Percent degradation of BK was determined by radioimmunoassay. The degradation products of BK after passing through the isolated rat-hearts were determined using RP-HPLC and mass spectroscopy. All the four doses of BK significantly decreased the perfusion pressure during their passage through the hearts. The percentage degradation of all four doses was decreased as the concentration of drug was increased, implying saturation of a fixed number of active sites involved in BK degradation. Bradykinin during a single passage through the hearts degraded to give [1-7]-BK as the major metabolite, and [1-8]-BK as a minor metabolite, detected on HPLC. Mass spectroscopy not only confirmed the presence of these two metabolites but also detected traces of [1-5]-BK and arginine. These findings showed that primarily ACE is the major cardiac enzyme involved in the degradation of bradykinin during a single passage through the coronary vascular of bed the healthy rat heart, while carboxypeptidase M may have a minor role.

Ability of iron acquisition of pathogenic microorganisms functions as a virulence factor. Candida albicans, a fungal pathogen that requires iron for growth, is susceptible to growth retardation by high-affinity iron binding proteins such as transferrin. Recently, we reported that C. albicans could utilize the heme as a part of heme-containing proteins dissociated by heme oxygenase, CaHMX1. In search of another pathway that C. albicans can use to bypass the growth regulation produced by iron limitation, this present study examined utilization of non-candidal siderophores such as Desferal and rhodotorulic acid (RA) for acquisition of inorganic iron by the fungus. C. albicans secreting no siderophores was cultured in iron-free (pretreated with apotransferrin for 24 h) (culture medium). Once growth of the yeast reached stasis from iron starvation, a siderophore was added to the culture media. Results showed that cultures containing apotransferrin within a dialysis membrane recovered growth to the level of untreated controls, whereas C. albicans yeast cells in direct contact with soluble iron-free (apo) transferrin recovered growth only partially. When static growth from iron limitation was reached, the addition of siderophore-apotransferrin complex to culture medium also permitted the yeast to recover growth from apotransferrin growth regulation. All the data show that C. albicans can utilize the non-candidal siderophores for iron acquisition under transferrin regulation as can pathogenic bacteria.

Salicornia herbacea L. (Chenopodiaceae) has been used as a seasoned vegetable by living in coastal areas. S. herbacea (SH) has been demonstrated to stimulate cytokine production, nitric oxide release, and to show anti-oxidative effect. In a series of investigations to develop potential anti-diabetic and/or anti-hyperlipidemic agents from Korean indigenous plants, 50% ethanol extract of Salicornia herbacea was found to prevent the onset of the hyperglycemia and hyperlipidemia induced by high fat diet in ICR mice. At 6 week old, the ICR mice were randomly divided into five groups; two control and three treatment groups. The control mice were to receive either a regular diet (RD) or high-fat diet (HFD), and the treatment groups were fed a high fat diet with either 350 mg/kg, 700 mg/kg of SH (SH350 and SH700) or 250 mg/kg of met-formin (MT250) for a 10-week period. SH not only reduced body weight but also corrected associated hyperglycemia and hyperlipidemia in a dose dependent manner. SH exerted beneficial effects on the plasma glucose and lipid homeostasis possibly ascribed to its specific effects on lipogenesis related genes (SREBP1a, FAS, GAPT), and PEPCK, glucose 6-phosphatase gene expressions in liver. Ethanol extract of S. herbacea has potential as a preventive agent for type 2 diabetes (and possibly hyperlipidemia) and deserves future clinical trial.