Actinoflavosides B-D, Flavonoid Type Glycosides from Tidal Mudflat-Derived Actinomyces.

Three new secondary metabolites, actinoflavosides B-D (1-3), were discovered in the culture broth of two actinomycete strains (JML48 and JMS33) that were isolated from tidal mudflat sediment in Muan, Republic of Korea. The planar structures of the actinoflavosides were elucidated by MS, UV, and NMR analyses. The stereochemistry of an aminosugar, 2,3,6-trideoxy-3-amino-ribopyranoside in the actinoflavosides was determined by J-based configuration analysis using values obtained from DQF-COSY experiments and modified Mosher's method. Actinoflavosides B-D (1-3) displayed antibacterial activity against Pseudomonas aeruginosa, and actinoflavoside D (3) significantly increased IL-2 production in mouse splenocytes.

Anti-Adipogenic and Anti-Obesity Effects of Gongmi Tea and Gongmi So Extract.

The prevalence of obesity has been increasing worldwide, and its pathogenesis is closely related to preadipo-cyte differentiation. Because the presence of obesity increases the risk of chronic disease, it is important to decrease exces-sive body fat accumulation. This study aimed to demonstrate the anti-adipogenesis and anti-obesity effects of gongmi tea and gongmi so extract. The 3T3-L1 preadipocyte cell line was stained with Oil red O, and the expression levels of peroxi-some proliferator-activated receptor-γ (PPARγ), adiponectin, and fatty acid-binding protein 4 (FABP4) were evaluated via Western blot analysis. A mouse model of obesity was developed by feeding C57BL/6 male mice a high-fat diet (HFD). Gongmi tea or gongmi so extract was orally administered at a dose of 200 mg/kg for 6 weeks. The mouse body weight was measured weekly during the study period, and the epididymal adipose tissue weight and blood serum were analyzed at the end of the study period. The gongmi tea and gongmi so extract did not exhibit toxicity in mice. Oil red O staining showed that gongmi tea significantly decreased excessive body fat accumulation. In addition, gongmi tea (300 µg/mL) significantly downregulated adipogenic transcription factors, such as PPARγ, adiponectin, and FABP4. In vivo tests indicated that oral administration of gongmi tea or gongmi so extract to C57BL/6 mice with HFD-induced obesity effectively decreased their body weight and epididymal adipose tissue. Gongmi tea and gongmi so extract have potent in vitro anti-adipogenic effects in 3T3-L1 cells and in vivo anti-obesity effects in mice with HFD-induced obesity.

Chromatographic Determination of the Absolute Configuration in Sanjoinine A That Increases Nitric Oxide Production.

A chiral derivatization strategy with phenylglycine methyl ester (PGME) was employed to develop a straightforward method to determine the absolute configurations of N,N-dimethyl amino acids. The PGME derivatives were analyzed using liquid chromatography-mass spectrometry to identify the absolute configurations of various N,N-dimethyl amino acids based on their elution time and order. The established method was applied to assign the absolute configuration of the N,N-dimethyl phenylalanine in sanjoinine A (4), a cyclopeptide alkaloid isolated from Zizyphi Spinosi Semen widely used as herbal medicine for insomnia. Sanjoinine A displayed production of nitric oxide (NO) in LPS-activated RAW 264.7 cells.

Cystargamides C and D, New Cyclic Lipopeptides From a Tidal Mudflat-Derived Streptomyces sp. JMS132.

Cystargamides C and D (2 and 3) were isolated from a marine actinomycete strain collected at Beolgyo, South Korea. The planar structures of the cystargamides were elucidated by 1/2D NMR, UV, and MS spectroscopic analyses. The absolute configurations of 2 and 3 were determined based on ROESY correlations and the advanced Marfey's methods. The structures of the compounds were elucidated as new lipodepsipeptides bearing six amino acids with an epoxy fatty acid side chain. For the first time, the nonribosomal peptide synthetase biosynthetic pathway of the cystargamides has been proposed using whole genome sequence analysis. The cystargamides displayed antioxidant effect in the DPPH and ABTS assay. The discovery of new cyclic lipopeptides, cystargamides C and D, from a tidal mudflat-derived Streptomyces sp. supported that marine bacteria have potential as source of bioactive natural products.

The chemical constituents of ethanolic extract from Stauntonia hexaphylla leaves and their anti-inflammatory effects.

Stauntonia hexaphylla (Lardizabalaceae) is an important medicinal plant in Korea, Japan, and China. Its leaves are used to treat many diseases because of their analgesic, sedative, and diuretic effects; however, there are few reports on their chemical constituents and biological activities. This study divided an ethanol extract into dichloromethane (DCM), ethyl acetate (EtOAc), and water fractions. Bioassay-guided fractionation of the ethanol extracts led to the isolation of seven compounds (1-7). To our knowledge, this is the first report of 1-7 from S. hexaphylla. The anti-inflammatory effects were investigated by suppressing cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in Western blots. The ethanol extract (20 µg/mL), DCM fraction (20 µg/mL), and compound 1 (10 µM) decreased COX-2 and iNOS expression significantly in LPS-induced RAW264.7 cells. These results suggest that S. hexaphylla leaves and compound 1 are useful candidates for treating inflammatory and other diseases.

Anti-allergic Inflammatory Effects of the Essential Oil From Fruits of Zanthoxylum coreanum Nakai.

Zanthoxylum coreanum Nakai is a rare shrub which grows in Korea and China. Pericarp of Z. coreanum has been used as a crude medicine, but there are few researches about the pharmacologic activities. The present study was designed to investigate the anti-allergic inflammatory activities of the essential oil from fruits of Zanthoxylum coreanum Nakai (ZCO). Our findings showed that ZCO inhibited both the IgE-antigen complex or PMA/A23187-induced ß-hexosaminidase release and IL-4 production dose-dependently in RBL-2H3 mast cells, and confirmed that ZCO at the tested concentrations did not show cytotoxicity to RBL-2H3 cells by MTS assay. Additionally, we found that ZCO showed the significant inhibition on LPS-induced overproduction of TNF-α, IL-6 and NO. Consistently, the protein levels of iNOS and COX-2 were also remarkably decreased by ZCO treatment. Herein, Our mechanistic studies revealed that ZCO significantly suppressed the activation of transcription factor NF-κB in PMA-activated 293T cells, and further inhibited NF-κB p65 translocation into the nucleus in LPS-stimulated RAW264.7 cells. Further investigation identified that ZCO down-regulated LPS-induced phosphorylation of MAPK (JNK, ERK, and p38) signal pathway. For incremental research, we established an DNCB-induced atopic dermatitis model in BALB/c mice, and found that ZCO remarkably inhibited DNCB-induced ear swelling and AD-like symptoms. Based on these findings, ZCO is suggested to have a therapeutic potential for the allergic inflammatory diseases.

Vibrio vulnificus RtxA1 Toxin Expression Upon Contact With Host Cells Is RpoS-Dependent.

The expression of virulence genes in bacteria is known to be regulated by various environmental and host factors. Vibrio vulnificus, an estuarine bacterium, experiences a dramatic environmental change during its infection process. We reported that V. vulnificus RtxA1 toxin caused acute cell death only when close contact to host cells was allowed. A sigma factor RpoS is a very important regulator for the maximal survival of pathogens under stress conditions. Here, we studied the role of RpoS in V. vulnificus cytotoxicity and mouse lethality. The growth of rpoS mutant strain was comparable to that of wild-type in heart infusion (HI) media and DMEM with HeLa cell lysate. An rpoS mutation resulted in decreased cytotoxicity, which was restored by in trans complementation. Interestingly, host contact increased the expression and secretion of V. vulnificus RtxA1 toxin, which was decreased and delayed by the rpoS mutation. Transcription of the cytotoxic gene rtxA1 and its transporter rtxB1 was significantly increased after host factor contact, whereas the activity was decreased by the rpoS mutation. In contrast, the rpoS mutation showed no effect on the transcriptional activity of a cytolytic heamolysin gene (vvhA). Additionally, the LD50 of the rpoS mutant was 15-fold higher than that of the wild-type in specific pathogen-free CD-1 female mice. Taken together, these results show that RpoS regulates the expression of V. vulnificus RtxA1 toxin and its transporter upon host contact.