Primary Cutaneous Nocardiosis Caused by Nocardia takedensis.

Nocardia species are aerobic, gram-positive, filamentous, partially acid-fast actinomycetes which are found worldwide in soil and decaying organic plant matter. When they infect human beings, they generally enter through the respiratory tract and then disseminate systemically. Rarely has a primary infection occurred as the result of direct inoculation. Isolation of Nocardia from clinical specimens and identification of species are difficult. But, with the introduction of new genetic technologies, reports of novel species of Nocardia have increased. We describe a case of cutaneous nocardiosis caused by Nocardia takedensis in an 87-year-old woman who was diagnosed by bacterial culture and 16S ribosomal RNA sequencing. N. takedensis has been described as a new species. This report describes the first clinical isolate of N. takedensis from a skin specimen in Korea.

2-Hydroxycinnamaldehyde inhibits the epithelial-mesenchymal transition in breast cancer cells.

Since epithelial-mesenchymal transition (EMT) plays a critical role in cancer progression and in maintaining cancer stem cell properties, EMT is emerging as a therapeutic target for inhibiting the metastatic progression of cancer cells. 2'-Hydroxycinnamaldehyde (HCA) and its derivative, 2'-benzoyloxycinnamaldehyde, have recently been suggested as promising therapeutic candidates for cancer treatment. The purpose of this study is to investigate the anti-metastatic effect of HCA on breast cancer and the molecular mechanisms by which HCA regulates the transcriptional program during EMT. HCA induces epithelial reversion at nanomolar concentrations by suppressing Snail via the nuclear translocalization of GSK-3ß, which results in the transcriptional upregulation of E-cadherin. HCA also activates the transcription factor KLF17, which suppresses Id-1, indicating that HCA inhibits EMT by multiple transcriptional programs. Further, HCA treatment significantly inhibits lung metastasis in a mouse orthotopic breast cancer model. This study demonstrates the anti-metastatic effect of the non-toxic natural compound HCA through attenuation of EMT in a breast cancer model.

Early growth response protein 1 upregulation and nuclear translocation by 2'-benzoyloxycinnamaldehyde induces prostate cancer cell death.

2'-Benzoyloxycinnamaldehyde (BCA) induces apoptosis in human cancer cells through ROS generation. BCA upregulates proapoptotic genes such as activating transcription factor 3 (ATF3), NSAID-activated gene 1 protein (NAG-1), and growth arrest and DNA-damage-inducible protein alpha (GADD45A) in prostate cancer cells. These genes are known to be induced by transcription factor early growth response protein 1 (EGR1). BCA induces significant EGR1 upregulation, while EGR1 knockdown decreases the induction of these genes with concurrent alleviation of cell death by BCA. Antioxidant glutathione pretreatment with BCA removes EGR1 expression increase, suggesting that EGR1 upregulation is dependent on oxidative stress generated by BCA. In prostate cancer cells, EGR1 localizes in the cytoplasm; however, BCA remarkably upregulates EGR1 nuclear translocalization, suggesting its possible effect as a transcriptional activator. BCA induces transient upregulation of importin-7 (IPO7) which is critical for EGR1 nuclear translocation, and IPO7 knockdown led to a significant decrease in chemosensitivity to BCA. Taken together, our findings suggest that BCA induces prostate cancer cell death via EGR1 upregulation and nuclear translocalization, followed by activation of proapoptotic target genes.

Stimulation of activity and expression of antioxidant enzymes by solvent fractions and isolated compound from Cedrela sinensis leaves in HepG2 cells.

Cedrela sinensis has been widely used in traditional Oriental medicine to treat a variety of diseases. However, little is known about the cellular actions by which this plant mediates its antioxidant effects. In this study, activity-guided fractionations of C. sinensis leaves were performed using column chromatographic techniques as well as biological assays with HepG2 cells. The ethanol (95%) extract of C. sinensis leaves was sequentially extracted with hexane, chloroform, ethyl acetate (EtOAc), butanol, and water, and the fractions were screened for their antioxidant potentials for scavenging radicals as well as inducing antioxidant enzyme activity and expression. The most potent antioxidant EtOAc fraction was further separated using chromatographic techniques including open column and high-performance liquid chromatography. Compound 1 from the EtOAc fraction showed strong radical scavenging activity with a 50% scavenging concentration value close to that of ascorbic acid and induced both the activity and expressions of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. Inhibitory effects on the phosphorylations of upstream mitogen-activated protein kinases such as c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38 were also observed after treatments with compound 1. Compound 1 was identified as quercitrin by (1)H- and (13)C-nuclear magnetic resonance techniques. Taken together, our findings demonstrated for the first time that C. sinensis leaves appear to be a useful source of a cytoprotective and chemopreventive agent that can stimulate the activity and expression of crucial antioxidant enzymes in cells.

Antioxidant potential of dimethyl lithospermate isolated from Salvia miltiorrhiza (red sage) against peroxynitrite.

Peroxynitrite (ONOO(-)) is a reactive oxidant formed from superoxide and nitric oxide that can readily oxidize cellular components, including essential protein, non-protein thiols, and DNA. ONOO(-) has contributed to the pathogenesis of diseases such as stroke, heart disease, Alzheimer's disease, and atherosclerosis. In this study, the ability of dimethyl lithospermate (DML), isolated from Salvia miltiorrhiza, to scavenge ONOO(-) and to protect cells against reactive species and ONOO(-) was investigated. The data obtained show that DML can efficiently scavenge native ONOO(-) as well as ONOO(-) derived from the ONOO(-) donor 3-morpholinosydnonimine hydrochloride. Spectrophotometric analysis revealed that DML led to decreased ONOO(-)-mediated nitration of tyrosine through electron donation. DML significantly inhibited nitration of bovine serum albumin by ONOO(-) in a dose-dependent manner. DML also manifested cytoprotection from cell damage induced by ONOO(-). The present study suggests that DML is an effective ONOO(-) scavenger and promotes cellular defense activity in the protection against ONOO(-)-involved diseases.

A phenolic glucoside isolated from Prunus serrulata var. spontanea and its peroxynitrite scavenging activity.

A new phenolic glucoside (1), pursargentoside, was isolated from the leaves of Prunus serrulata var. spontanea, along with three other known compounds, orobol 7-omicron-glucoside (2), 1beta, 2alpha, 3alpha, 24-tetrahydroxy-urs-12-en-28-oic acid (3), and chlorogenic acid (4). The structure of pursargentoside (1) was identified by spectroscopic data analysis including 1D and 2D NMR spectroscopy, as 2-omicron-beta-(6'-benzoyl)-glucopyranosyl omicron-(Z)-coumaric acid. Compounds 1, 2, and 4 exhibited ONOO scavenging activity, whereas compound 3 was determined to be virtually inactive.

A sphingolipid and tyrosinase inhibitors from the fruiting body of Phellinus linteus.

This paper for the first time reports the isolation of 5 compounds from Phellinus linteus. A sphingolipid (1) and two tyrosinase inhibitory compounds (2, 3) along with two carboxylic acids (4, 5), were isolated from the fruiting body of Phellinus linteus (Berk & Curt) Aoshima. The structure of compound 1 was identified as 1-omicron-beta-D-glucopyranosyl-(2S, 3R, 4E, 8E)-2-[(2R)-2-hydroxyhexadecanoylamino]-9-methyl-4,8-octadecadiene-1,3-diol, known as cerebroside B, based on spectroscopic methods such as 1 D and 2D NMR as well as by acid hydrolysis. Compounds 2 -5 were identified as protocatechualdehyde (2), 5-hydroxymethyl-2-furaldehyde (HMF) (3), succinic acid (4), and fumaric acid (5) based on the spectroscopic evidence. Compounds 2 and 3 inhibited the oxidation of L-tyrosine catalyzed by mushroom tyrosinase with an IC50 of 0.40 and 90.8 microg/mL, respectively. The inhibitory kinetics, which were analyzed by the Lineweaver-Burk plots, were found to be competitive and noncompetitive inhibitors with a Ki of 1.1 microM and 1.4 mM, respectively.

Inhibitory phlorotannins from the edible brown alga Ecklonia stolonifera on total reactive oxygen species (ROS) generation.

Reactive oxygen species (ROS) play an important role in the pathogenesis of many human degenerative diseases such as cancer, aging, arteriosclerosis, and rheumatism. Much attention has been focused on the development of safe and effective antioxidants. To discover sources of antioxidative activity in marine algae, extracts from 17 kinds of seaweed were screened for their inhibitory effect on total ROS generation in kidney homogenate using 2',7'-dichlorofluorescein diacetate (DCFH-DA). ROS inhibition was seen in three species: Ulva pertusa, Symphyocladia latiuscula, and Ecklonia stolonifera. At a final concentration of 25 microg/mL, U. pertusa inhibited 85.65+/-20.28% of total ROS generation, S. latiscula caused 50.63+/-0.09% inhibitory, and the Ecklonia species was 44.30+/-7.33% inhibition. E. stolonifera Okamura (Laminariaceae), which belongs to the brown algae, has been further investigated because it is commonly used as a foodstuff in Korea. Five compounds, phloroglucinol (1), eckstolonol (2), eckol (3), phlorofucofuroeckol A (4), and dieckol (5), isolated from the ethyl acetate soluble fraction of the methanolic extract of E. stolonifera inhibited total ROS generation.

Tyrosinase inhibitors isolated from the edible brown alga Ecklonia stolonifera.

Extracts from seventeen seaweeds were determined for tyrosinase inhibitory activity using mushroom tyrosinase with L-tyrosine as a substrate. Only one of them, Ecklonia stolonifera OKAMURA (Laminariaceae) belonging to brown algae, showed high tyrosinase inhibitory activity. Bioassay-guided fractionation of the active ethyl acetate (EtOAc) soluble fraction from the methanolic extract of E. stolonifera, led us to the isolation of phloroglucinol derivatives [phloroglucinol (1), eckstolonol (2), eckol (3), phlorofucofuroeckol A (4), and dieckol (5)]. Compounds 1 approximately 5 were found to inhibit the oxidation of L-tyrosine catalyzed by mushroom tyrosinase with IC50 values of 92.8, 126, 33.2, 177, and 2.16 microg/mL, respectively. It was compared with those of kojic acid and arbutin, well-known tyrosinase inhibitors, with IC50 values of 6.32 and 112 microg/ mL, respectively. The inhibitory kinetics analyzed from Lineweaver-Burk plots, showed compounds 1 and 2 to be competitive inhibitors with Ki of 2.3x10(-4) and 3.1x10(-4) M, and compounds 3 approximately 5 to be noncompetitive inhibitors with Ki of 1.9x10(-5), 1.4x10(-3) and 1.5x10(-5) M, respectively. This work showed that phloroglucinol derivatives, natural compounds found in brown algae, could be involved in the control of pigmentation in plants and other organisms through inhibition of tyrosinase activity using L-tyrosine as a substrate.

A new phlorotannin from the brown alga Ecklonia stolonifera.

A new phlorotannin, named eckstolonol (1), was isolated from the EtOAc soluble fraction of the methanolic extract of the brown alga, Ecklonia stolonifera OKAMURA, along with three known phlorotannins, eckol (2), phlorofucofuroeckol A (3), and dieckol (4). The structure of eckstolonol was identified as 5,8,13,14-tetraoxa-pentaphene-1,3,6,9,11-pentaol on the basis of spectroscopic evidence. The new compound was found to be a radical scavenger on the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical.

Further isolation of antioxidative (+)-1-hydroxypinoresinol-1-O-beta-D-glucoside from the rhizome of Salvia miltiorrhiza that acts on peroxynitrite, total ROS and 1,1-diphenyl-2-picrylhydrazyl radical.

A furanofuranoid lignan glycoside, with radical scavenging on peroxynitrite, total reactive oxygen species (ROS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, was isolated from the rhizome of Salvia miltiorrhiza and characterized as (+)-1-hydroxypinoresinol-1-O-beta-D-glucoside based on spectroscopic evidence. The compound exhibited peroxynitrite, total ROS and DPPH radical scavenging activities with IC50 values of 3.23 +/- 0.04, 2.26 +/- 0.07 and 32.3 +/- 0.13 microM, respectively. Penicillamine, Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid) and L-ascorbic acid, acting as positive controls, showed radical scavenging activities with IC50 values of 6.72 +/- 0.25, 1.43 +/- 0.04 and 11.4 +/- 0.07 microM, respectively.