Inhibition of human cervical cancer development through p53-dependent pathways induced by the specified triple helical ß-glucan.

This study demonstrates that the purified ß-glucan (LNT) with a triple helix and relatively narrow molecular weight distribution, extracted and purified from artificially cultured Lentinus edodes, showed a significant cervical cancer inhibition with little cytotoxicity against normal cells in vitro and in vivo. From the in vitro data, the potential mechanism of anti-cervical cancer was preliminarily revealed as follows: LNT was firstly recognized by the human cervical cancer cell line of Hela and induced cell proliferation inhibition through p21 and apoptosis via a mitochondrion-dependent pathway by targeting the tumor suppressor of p53, indicated by an increase in reactive oxygen species (ROS) generation and a loss of mitochondrial membrane potential (Δψm), in a significant dosage-dependent manner. Meanwhile, LNT repressed tumor growth with an inhibition ratio of 61.2 % and induced tumor cell apoptosis through endogenous MDM2/p53/Bax/mitochondrion signal pathway by up-regulating the expression of p53, Bax, Cyt. c, caspase 9, and caspase 3, as well as down-regulating Bcl-2, MDM2, and PARP1 levels in Hela cells-transplanted BALB/c nude mice. This study provides a scientific basis for the clinical treatment of cervical cancer with LNT as a potential drug candidate characterized by the triple helix and specified molecular weight with a relatively narrow distribution.

The detection, purity and structural properties of partially soluble mushroom and cereal ß-D-glucans: A solid-state NMR study.

ß-D-glucans are proposed to have many health benefits. It is therefore important to have methods which can distinguish these from other carbohydrates present in natural products, as well as giving glucan content and structural information. Correlations between features in the CP/MAS spectra of ß-D-glucans and enzyme assay determined ß-D-glucan content were generally found to be poor. The ß-D-glucan in dry and hydrated forms of the mushroom Ganoderma lucidum was investigated in detail by spectral peak fitting to the anomeric carbon C1 region in CP/MAS NMR spectra. Hydrated samples gave spectra with enhanced resolution and suggested that a clear distinction between ß-D-glucans and other carbohydrates could be possible in the anomeric carbon C1 region. Chemical shift values for a range of carbohydrate polymers, which can be found alongside ß-D-glucans, as well as the values for various linkages are given. Contamination by other carbohydrates and buffer salts is discussed.

Kinetics of conversion of dihydroxyacetone to methylglyoxal in New Zealand manuka honey: Part V - The rate determining step.

Monomer formation from dimeric DHA has previously been suggested as the rate-determining step in formation of methylglyoxal, the bioactive component in manuka honey. This step was studied by 1H NMR in DMSO­d6. First order reaction rate was 3.31 × 10-3 ±â€¯9.1 × 10-4 min-1. Upon titration with D2O, little change was observed until ∼15 mass% whereupon an exponential increase in rate occurred until indistinguishable from the rate observed in water. Acid or base caused rate accelerations. Theoretical modelling confirmed the existence of acid and base-catalysed mechanisms for dimer decomposition and the structures of two intermediates observed. In honey it is likely the base-catalysed decomposition predominates with water as catalyst but there is little rate acceleration at the levels of water present normally in honey however a small increase in the mass% of water in the honey could cause significant rate acceleration of dimer decomposition and hence formation of methylglyoxal.

Solanum paniculatum L. decreases levels of inflammatory cytokines by reducing NFKB, TBET and GATA3 gene expression in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Solanum paniculatum L., popularly known as jurubeba, is a common subtropical plant from Brazil, Paraguay, Bolivia and Argentina, that is used in folk medicine for the treatment of anemia, gastrointestinal disorders and inflammatory conditions in general. In addition to that, an ethnobotanical survey in "Todos os Santos" Bay have pointed out S. paniculatum as an herb to treat asthma. Previous publications have shown that S. paniculatum possesses antibiotic, antioxidant and modulatory effects on gastric acid secretion; however, its anti-inflammatory potential remains unexplored. AIM OF THE STUDY: Herein, we analyzed the S. paniculatum fruits hexane extract (SpE) for the presence of stigmasterol and ß-sitosterol and investigated the anti-inflammatory effect of SpE in vitro. MATERIALS AND METHODS: SpE was subjected to high-performance liquid chromatography (HPLC) for standardization and quantification of stigmasterol and ß-sitosterol. Spleen cells from BALB/c mice were cultivated and stimulated with pokeweed mitogen and also exposed to 15, 30 and 60µg/mL of SpE. Following treatment, levels of IFN-γ, IL-4 and IL-10 in the culture supernatants were assessed by ELISA. We also evaluated nitric oxide (NO) production by murine LPS-stimulated peritoneal macrophages using the Griess technique. In addition, the ability of SpE to stabilize membranes was assessed using a model of hemolysis induced by heat on murine erythrocytes. Gene expression of Th1-cell-specific Tbx21 transcription factor (TBET), zinc-finger transcription factor-3 (GATA3), and nuclear factor-κB (NFKB) in murine spleen cells were assessed by quantitative Polymerase Chain Reaction (qRT-PCR). RESULTS: SpE at 15, 30 and 60µg/mL significantly attenuated cell proliferation, decreased IL-4 release, reduced NO production and improved erythrocyte membrane stabilization in a concentration-dependent manner. SpE was also able to decrease the release of IFN-γ without altering IL-10 levels. The mechanism whereby SpE decreased inflammatory markers may be related to the reduction of NFKB, TBET and GATA3 gene expression. CONCLUSIONS: This study is the first to test the anti-inflammatory action of S. paniculatum. Herein, we provided evidence for the popular use of S. paniculatum in inflammatory conditions. Additional studies must be conducted to further explore the anti-inflammatory potential of SpE and to elucidate possible clinical applications.

A hyperbranched ß-d-glucan with compact coil conformation from Lignosus rhinocerotis sclerotia.

An alkali-soluble polysaccharide was extracted from Lignosus rhinocerotis sclerotia (LRP). Its structural characteristics were determined by GC-MS, FT-IR, GC, 1D and 2D NMR combined with Smith degradation and methylation analysis. The LRP had a (1→3)-ß-d-Glcp backbone with every three residues bearing a (1→6)-linked and hyperbranched side chain that contained three (1→6)-ß-d-Glcp residues as secondary main chain and two terminal ß-d-Glcp residues linked at O3. The degree of branching was 0.76 from GC-MS analysis, implying a highly branched structure for LRP. The Mw, z1/2, Rh and [η] values of LRP in 0.25M LiCl/DMSO were measured by SEC-MALLS-Vis-RI combination technology to be 2.88×105g/mol, 30.36nm, 22.34nm and 131.50ml/g, respectively. Furthermore, the exponent α of [η]-Mw, ß of z1/2-Mw, the fractal dimension df and molecular parameter ρ were determined to be 0.20, 0.33, 2.50 and 1.36, demonstrating that the LRP was a hyperbranched polysaccharide and adopted a compact coil conformation in LiCl/DMSO.

A comb-like branched ß-D-glucan produced by a Cordyceps sinensis fungus and its protective effect against cyclophosphamide-induced immunosuppression in mice.

An exopolysaccharide (EPS) was fractionated from fermentation media of a Cordyceps sinensis fungus (Cs-HK1) by ethanol precipitation at 2/5 volume ratio of ethanol/media. Its structural characteristics were elucidated by FT-IR, GC, GC-MS, 1D and 2D NMR combined with periodate oxidation, Smith degradation, partial acid hydrolysis, and methylation analysis. Furthermore, the immunomodulatory activity of EPS was evaluated by the model of cyclophosphamide-induced immunosuppression. The results from monosaccharide composition and partial acid hydrolysis indicated that EPS almost consisted of glucose excluding a trace amount of mannose. GC-MS and NMR analysis further confirmed EPS had a linear backbone of (1→3)-ß-D-glucopyranosyl residues with a single (1→6)-ß-D-glucopyranosyl side-branching unit for every three ß-D-glucopyranosyl residues, showing a comb-like ß-D-glucan with short and intensive branches, which was responsible for high viscosity. Moreover, EPS could significantly enhance immune organs and stimulate the release of major cytokines TNF-α and INF-γ, suggesting that EPS exhibited protective effect in immunocompromised mice.

Investigations of bisacodyl with modified ß-cyclodextrins: Characterization, molecular modeling, and effect of PEG.

Bisacodyl inclusion into hydroxypropyl-ß-cyclodextrin and 2,6-di-O-methyl-ß-cyclodextrin cavities was experimentally and theoretically investigated, and the effect of PEG 4000 on these inclusions was studied. Isothermal calorimetry titration curves indicated that the binary inclusion processes are enthalpy- and entropy-driven. The solid-state complexes were fully characterized by FT-IR, XRPD, DSC and SEM analyses. FT-IR, (1)H NMR, and ROESY studies provided the most favorable encapsulation modes of binary complexes, and results were further confirmed by molecular docking and molecular dynamics studies. The presence of PEG 4000 slightly enhanced encapsulation efficiency, solubility and dissolution rates of the binary complexes. In vivo studies showed that complexes with CDs markedly accelerated gastrointestinal transit time compared with pure bisacodyl, whereas addition of PEG 4000 showed no further significant improvement of the bioavailability.