Selected Extracts of Chinese Herbal Medicines: Their Effect on NF-κB, PPARα and PPARγ and the Respective Bioactive Compounds

Chinese herbal medicinal (CHM) extracts from fourteen plants were investigated in cell-based in vitro assays for their effect on nuclear factor κB (NF-κB), a key regulator of inflammation, as well as on peroxisome proliferator-activated receptors (PPARs) being key regulators of genes involved in lipid and glucose metabolism. 43% of the investigated CHMs showed NF-κB inhibitory and 50% PPARα and PPARγ activating effects. Apolar extracts from cortex and flos of Albizia julibrissin Durazz. and processed rhizomes of Arisaema sp. and Pinellia ternata (Thunb.) Breit. that effectively inhibited TNF-α-induced NF-κB activation and dose-dependently activated PPARα and PPARγ were further investigated. Bioassay-guided fractionation and analysis by GC-MS led to the identification of fatty acids as PPAR agonists, including linoleic and palmitic acid

The Herbal Drug Melampyrum pratense

Melampyrum pratense L. (Koch) is used in traditional Austrian medicine for the treatment of different inflammation-related conditions. In this work, we show that the extracts of M. pratense stimulated peroxisome proliferator-activated receptors- (PPARs-)α and -γ that are well recognized for their anti-inflammatory activities. Furthermore, the extract inhibited the activation of the proinflammatory transcription factor NF-κB and induction of its target genes interleukin-8 (IL-8) and E-selectin in vitro. Bioassay-guided fractionation identified several active flavonoids and iridoids including melampyroside and mussaenoside and the phenolic compound lunularin that were identified in this species for the first time. The flavonoids apigenin and luteolin were distinguished as the main components accountable for the anti-inflammatory properties. Apigenin and luteolin effectively inhibited tumor necrosis factor α (TNF-α)-induced NF-κB-mediated transactivation of a luciferase reporter gene. Furthermore, the two compounds dose-dependently reduced IL-8 and E-selectin protein expression after stimulation with lipopolysaccharide (LPS) or TNF-α in endothelial cells (ECs). The iridoids melampyroside and mussaenoside prevented the elevation of E-selectin in LPS-stimulated ECs. Lunularin was found to reduce the protein levels of the proinflammatory mediators E-selectin and IL-8 in ECs in response to LPS. These data validate the ethnomedical use of M. pratense for the treatment of inflammatory conditions and point to the constituents accountable for its anti-inflammatory activity

The Globular Cluster System of NGC 1399. II. Kinematics of a Large Sample of Globular Clusters

We study the kinematics and dynamics of the globular cluster system of NGC 1399, the central galaxy of the Fornax cluster. The observational data consists of medium resolution spectra, obtained at the Very Large Telescope. Our sample comprises 468 radial velocities in the magnitude range 20 < m_R < 23. This is the largest sample of globular cluster velocities around any galaxy obtained so far. The radial range is 2 arcmin < r < 9 arcmin, corresponding to 11 kpc to 50 kpc of galactocentric distance. There is the possibility that unbound clusters and/or objects in the foreground contaminate the NGC 1399 cluster sample. Under strong error selection, practically no objects are found with velocities lower than 800 km/s or higher than 2000 km/s. Since the extreme velocities influence the velocity dispersion considerably, uncertainty regarding the exact value of the dispersion remains. Within the above velocity limits, we derive a projected velocity dispersion for the total sample of 274+-9 km/s which within the uncertainties remains constant over the entire radial range. Without any velocity restriction, it increases to 325 km/s. Blue and red clusters show different dispersions corresponding to their different surface density profiles. Spherical models point to a circular velocity of 415+-30$ km/s, assuming isotropy for the red clusters. This value is constant out to 40 kpc. The inferred dark halo potential can be well represented by a logarithmic potential. Also a halo of the NFW type fits well to the observations. Some mass profiles derived from X-ray analyses do not agree with a constant circular velocity within our radial range, irrespective of its exact value.Comment: 38 pages, 20 figures, accepted by A

A fast and robust hepatocyte quantification algorithm including vein processing

<p>Abstract</p> <p>Background</p> <p>Quantification of different types of cells is often needed for analysis of histological images. In our project, we compute the relative number of proliferating hepatocytes for the evaluation of the regeneration process after partial hepatectomy in normal rat livers.</p> <p>Results</p> <p>Our presented automatic approach for hepatocyte (HC) quantification is suitable for the analysis of an entire digitized histological section given in form of a series of images. It is the main part of an automatic hepatocyte quantification tool that allows for the computation of the ratio between the number of proliferating HC-nuclei and the total number of all HC-nuclei for a series of images in one processing run. The processing pipeline allows us to obtain desired and valuable results for a wide range of images with different properties without additional parameter adjustment. Comparing the obtained segmentation results with a manually retrieved segmentation mask which is considered to be the ground truth, we achieve results with sensitivity above 90% and false positive fraction below 15%.</p> <p>Conclusions</p> <p>The proposed automatic procedure gives results with high sensitivity and low false positive fraction and can be applied to process entire stained sections.</p

Natural products in drug discovery: advances and opportunities

Natural products and their structural analogues have historically made a major contribution to pharmacotherapy, especially for cancer and infectious diseases. Nevertheless, natural products also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization, which contributed to a decline in their pursuit by the pharmaceutical industry from the 1990s onwards. In recent years, several technological and scientific developments — including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances — are addressing such challenges and opening up new opportunities. Consequently, interest in natural products as drug leads is being revitalized, particularly for tackling antimicrobial resistance. Here, we summarize recent technological developments that are enabling natural product-based drug discovery, highlight selected applications and discuss key opportunities

Evolution of Thermally Pulsing Asymptotic Giant Branch Stars V: Constraining the Mass Loss and Lifetimes of Intermediate Mass, Low Metallicity AGB Stars

Thermally pulsing asymptotic giant branch (TP-AGB) stars are relatively short lived (less than a few Myr), yet their cool effective temperatures, high luminosities, efficient mass loss, and dust production can dramatically affect the chemical enrichment histories and the spectral energy distributions of their host galaxies. The ability to accurately model TP-AGB stars is critical to the interpretation of the integrated light of distant galaxies, especially in redder wavelengths. We continue previous efforts to constrain the evolution and lifetimes of TP-AGB stars by modeling their underlying stellar populations. Using Hubble Space Telescope (HST) optical and near-infrared photometry taken of 12 fields of 10 nearby galaxies imaged via the Advanced Camera for Surveys Nearby Galaxy Survey Treasury and the near-infrared HST/SNAP follow-up campaign, we compare the model and observed TP-AGB luminosity functions as well as the ratio of TP-AGB to red giant branch stars. We confirm the best-fitting mass-loss prescription, introduced by Rosenfield et al., in which two different wind regimes are active during the TP-AGB, significantly improves models of many galaxies that show evidence of recent star formation. This study extends previous efforts to constrain TP-AGB lifetimes to metallicities ranging -1.59 less than or similar to [Fe/H] &lt;= -0.56 and initial TP-AGB masses up to similar to 4 M-circle dot, which include TP-AGB stars that undergo hot-bottom burning. \ua9 2016. The American Astronomical Society. All rights reserved

Picomole scale stereochemical analysis of sphingosines and dihydrosphingosines

We have developed a simple picomole (low nanogram) scale HPLC scheme which can separate all eight isomers of sphingosine and dihydrosphingosine thus leading to the identification of their relative and absolute configurations. The amino group of the sample is derivatized to its fluorescent N-naphthimide which is analyzed by normal and chiral phase HPLC, coupled with fluorescence peak detection. If necessary, the results of this HPLC method can be further corroborated by measurements of circular dichroic (CD) spectra of the N-naphthimido-derivatives and/or N,O-chromophoric derivatives. Copyright (C) 1996 Elsevier Science Lt