Bupleurum chinense Roots: a Bioactivity-Guided Approach toward Saponin-Type NF-κB Inhibitors

The roots of Bupleurum chinense have a long history in traditional medicine to treat infectious diseases and inflammatory disorders. Two major compounds, saikosaponins A and D, were reported to exert potent anti-inflammatory activity by inhibiting NF-κB. In the present study, we isolated new saikosaponin analogues from the roots of B. chinese interfering with NF-κB activity in vitro. The methanol-soluble fraction of the dichloromethane extract of Radix Bupleuri was subjected to activity-guided isolation yielding 18 compounds, including triterpenoids and polyacetylenes. Their structures were determined by spectroscopic methods as saikogenin D (1), prosaikogenin D (2), saikosaponins B2 (3), W (4), B1 (5), Y (6), D (7), A (8), E (9), B4 (10), B3 (11), and T (12), saikodiyne A (13), D (14), E (15) and F (16), falcarindiol (17), and 1-linoleoyl-sn-glycero-3-phosphorylcholine (18). Among them, 4, 15, and 16 are new compounds, whereas 6, previously described as a semi-synthetic compound, is isolated from a natural source for the first time, and 13–17 are the first reports of polyacetylenes from this plant. Nine saponins/triterpenoids were tested for inhibition of NF-κB signaling in a cell-based NF-κB-dependent luciferase reporter gene model in vitro. Five of them (1, 2, 4, 6, and 8) showed strong (> 50%, at 30 µM) NF-κB inhibition, but also varying degrees of cytotoxicity, with compounds 1 and 4 (showing no significant cytotoxicity) presenting IC50 values of 14.0 µM and 14.1 µM in the cell-based assay, respectively

Polyacetylenes from Notopterygium incisum–New Selective Partial Agonists of Peroxisome Proliferator-Activated Receptor-Gamma

Peroxisome proliferator-activated receptor gamma (PPARγ) is a key regulator of glucose and lipid metabolism and therefore an important pharmacological target to combat metabolic diseases. Since the currently used full PPARγ agonists display serious side effects, identification of novel ligands, particularly partial agonists, is highly relevant. Searching for new active compounds, we investigated extracts of the underground parts of Notopterygium incisum, a medicinal plant used in traditional Chinese medicine, and observed significant PPARγ activation using a PPARγ-driven luciferase reporter model. Activity-guided fractionation of the dichloromethane extract led to the isolation of six polyacetylenes, which displayed properties of selective partial PPARγ agonists in the luciferase reporter model. Since PPARγ activation by this class of compounds has so far not been reported, we have chosen the prototypical polyacetylene falcarindiol for further investigation. The effect of falcarindiol (10 µM) in the luciferase reporter model was blocked upon co-treatment with the PPARγ antagonist T0070907 (1 µM). Falcarindiol bound to the purified human PPARγ receptor with a Ki of 3.07 µM. In silico docking studies suggested a binding mode within the ligand binding site, where hydrogen bonds to Cys285 and Glu295 are predicted to be formed in addition to extensive hydrophobic interactions. Furthermore, falcarindiol further induced 3T3-L1 preadipocyte differentiation and enhanced the insulin-induced glucose uptake in differentiated 3T3-L1 adipocytes confirming effectiveness in cell models with endogenous PPARγ expression. In conclusion, we identified falcarindiol-type polyacetylenes as a novel class of natural partial PPARγ agonists, having potential to be further explored as pharmaceutical leads or dietary supplements

Mass-to-light ratio gradients in early-type galaxy haloes

Since the near future should see a rapidly expanding set of probes of the halo masses of individual early-type galaxies, we introduce a convenient parameter for characterising the halo masses from both observational and theoretical results: \dML, the logarithmic radial gradient of the mass-to-light ratio. Using halo density profiles from LCDM simulations, we derive predictions for this gradient for various galaxy luminosities and star formation efficiencies $\epsilon_{SF}$. As a pilot study, we assemble the available \dML\ data from kinematics in early-type galaxies - representing the first unbiassed study of halo masses in a wide range of early-type galaxy luminosities - and find a correlation between luminosity and \dML, such that the brightest galaxies appear the most dark-matter dominated. We find that the gradients in most of the brightest galaxies may fit in well with the LCDM predictions, but that there is also a population of fainter galaxies whose gradients are so low as to imply an unreasonably high star formation efficiency $\epsilon_{SF} > 1$. This difficulty is eased if dark haloes are not assumed to have the standard LCDM profiles, but lower central concentrations.Comment: 17 pages, 13 figures. Accepted for publication on MNRA

Antifungal, anti-inflammatory and cytotoxicity activities of three varieties of Labisia pumila benth : from microwave obtained extracts.

Background: Labisia pumila, locally known as Kacip Fatimah, is a forest-floor plant that has tremendous potential in the herbal industry. It is one of the five herbal plants identified by the government as one of the national key economic areas to be developed for commercial purposes. There are three varieties of L. pumila namely, L. pumila var. pumila, L. pumila var. alata and L. pumila var. lanceolata and each has its own use.Methods: The leaves and roots of the three varieties of L. pumila Benth. were extracted using microwave assisted extraction (MAE). Antifungal activity of all plant extracts were characterized against Fusarium sp., Candida sp. and Mucor using the agar diffusion disc. Anti-inflammatory assays were performed using NO production by macrophage RAW 264.7 cell lines induced by LPS/IFN-g and cytotoxic activity was determined using several cancer cell lines and one normal cell line.Results: The overall result demonstrated that leaf and root extracts of all three varieties of L. pumila exhibited moderate to appreciable antifungal activity against Fusarium sp., Candida sp. and Mucor compared to streptomycin used as positive control. Leaf and root extracts of all varieties significantly decreased NO release. However, the root extracts showed higher activity compared to the leaf extracts. Cytotoxic activity against MCF-7, MDA-MB-231 and Chang cell lines were observed with all extracts.Conclusions: These findings suggest the potential use of L. pumila Benth. as a natural medicine and indicated the possible application of this medicinal plant such anti inflammatory activity and cytotoxic agents

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