The role of chalcones: helichrysetin,xanthohumol, and flavokawin-C in promoting neurite outgrowth in PC12 Adh cells

Chalcones are a group of compounds widely distributed in plant kingdom. The aim of this study was to assess the neurite outgrowth stimulatory activity of selected chalcones, namely helichrysetin, xanthohumol and flavokawin-C. Using adherent rat pheochromocytoma (PC12 Adh) cells, the chalcones were subjected to neurite outgrowth assay and the extracellular nerve growth factor (NGF) levels were determined. Xanthohumol (10 μg/mL) displayed the highest (p < 0.05) percentage of neurite-bearing PC12 Adh cells and the highest (p < 0.05) NGF level in the culture medium of xanthohumol-treated cells. While, helichrysetin induced a moderately high numbers of neurite-bearing cells, flavokawin-C did not stimulate neurite outgrowth. This work supports the potential use of xanthohumol as a potential neuroactive compound to stimulate neurite outgrowth.     

Regulation of neurite outgrowth by intermittent irradiation of visible light

The effect of neurite outgrowth of PC12 cells on collagen-coated glass plates under intermittent light irradiation at 525 nm and 0.4 mW/cm2 of intensity was investigated. Neurite outgrowth of PC12 cells was significantly suppressed when PC12 cells were cultivated under intermittent light irradiation with a total irradiation time of more than 2 min/h. No temperature increase was observed in the culture medium under either continuous or intermittent light irradiation. Therefore, suppression of neurite outgrowth under light irradiation was not due to the increase of temperature in the culture medium, but rather the effect of light on the PC12 cells, especially the signal transmittance of light to PC12 cells. The light irradiation interval also affected the neurite outgrowth of PC12 cells when the total irradiation time was constant. A high extension ratio of neurite outgrowth was observed under a long time interval of nonirradiation between light irradiations (1 min of irradiation every hour) as compared with frequent light irradiation intervals (5 s of irradiation every 5 min) with the same total irradiation period per hour. The neurite outgrowth ratio was thought to be dependent on the light intensity, the total time of light irradiation in the intermittent light irradiation, and the interval of light irradiation in the intermittent light irradiation.     

Synthesis and neurite outgrowth promoting activity of vibsanin B derivatives

Intramolecular hetero-DA reaction and unexpected retro-aldol like ring opening reaction were performed. As a result, six derivatives with different skeletons of vibsane-type diterpenoids were synthesized from vibsanin B within three steps. Moreover, compounds 2, 3, and 6 enhanced the neurite outgrowth of NGF-mediated PC12 cells.     

Withanolide derivatives from the roots of Withania somnifera and their neurite outgrowth activities

Five new withanolide derivatives (1, 9-12) were isolated from the roots of Withania somnifera together with fourteen known compounds (2-8, 13-19). On the basis of spectroscopic and physiochemical evidence, compounds 1 and 9-12 were determined to be (20S,22R)-3 alpha,6 alpha-epoxy-4 beta,5 beta,27-trihydroxy-1-oxowitha-24-enolide (1), 27-O-beta-D-glucopyranosylpubesenolide 3-O-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranoside (withanoside VIII, 9), 27-O-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosylpubesenolide 3-O-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranoside (withanoside IX, 10), 27-O-beta-D-glucopyranosylpubesenolide 3-O-beta-D-glucopyranoside (withanoside X, 11), and (20R,22R)-1 alpha,3 beta,20,27-tetrahydroxywitha-5,24-dienolide 3-O-beta-D-glucopyranoside (withanoside XI, 12). Of the isolated compounds, 1, withanolide A (2), (20S,22R)-4 beta,5 beta,6 alpha,27-tetrahydroxy-1-oxowitha-2,24-dienolide (6), withanoside IV (14), withanoside VI (15) and coagulin Q (16) showed significant neurite outgrowth activity at a concentration of 1 microM on a human neuroblastoma SH-SY5Y cell line.     

Secretin induces neurite outgrowth of PC12 through cAMP-mitogen-activated protein kinase pathway

The gastrointestinal functions of secretin have been fairly well established. However, its function and mode of action within the nervous system remain largely unclear. To gain insight into this area, we have attempted to determine the effects of secretin on neuronal differentiation. Here, we report that secretin induces the generation of neurite outgrowth in pheochromocytoma PC12 cells. The expressions of Tau and beta-tubulin, neuronal differentiation markers, are increased upon secretin stimulation. In addition, secretin induces sustained mitogen-activated protein kinase (MAPK) activation and also stimulates the cAMP secretion. Moreover, the neurite outgrowth elicited by secretin is suppressed to a marked degree in the presence of either PD98059, a specific MAPK/ERK kinase (MEK) inhibitor, or H89, a specific protein kinase A (PKA) inhibitor. Taken together, these observations demonstrate that secretin induces neurite outgrowth of PC12 cells through cAMP- MAPK pathway, and provide a novel insight into the manner in which secretin participates in neuritogenesis.     

Littorachalcone,a new enhancer of NGF-mediated neurite outgrowth,from Verbena littoralis

A new dihydrochalcone dimer, 2',4',3",2"',4"'-pentahydroxy-4-O-4"-tetrahydrobichalcone, given the name littorachalcone, was isolated from the aerial parts of Verbena littoralis H. B. K. along with two known flavonoids 4'-hydroxywogonin and 8,3'-dimethoxy-5,7,4'-trihydroxyflavone. Littorachalcone caused a significant enhancement of nerve growth factor-mediated neurite outgrowth from PC12D cells.     

Thermoresponsive polymer brush on monolithic-silica-rod for the high-speed separation of bioactive compounds

Poly(N-isopropylacrylamide), one of the most utilized thermoresponsive polymers, brush-grafted monolithic-silica columns were prepared through surface-initiated atom transfer radical polymerization (ATRP) for effective thermoresponsive-chromatography matrices. ATRP initiator was grafted on monolithic silica-rod surfaces by flowing a toluene solution containing ATRP initiator into monolithic silica-rod columns. N-Isopropylacrylamide (IPAAm) monomer and CuCl/CuCl(2)/Me(6)TREN, an ATRP catalytic system, were dissolved in 2-propanol, and the reaction solution was pumped into the preprepared initiator-modified columns at 25 °C for 16 h. The constructed PIPAAm-brush structure on the monolithic silica-rod surface was confirmed by XPS, elemental analysis, SEM observation, and GPC measurement of grafted PIPAAm. The prepared monolithic silica-rod columns were also characterized by chromatographic analysis. PIPAAm-brush-modified monolithic silica-rod columns were able to separate hydrophobic steroids with a short analysis time (10 min), compared to PIPAAm-brush-modified silica-beads-packed columns, because of the horizontally limited diffusion path length of monolithic supporting materials. Additionally, diluted PIPAAm-brush monolithic silica-rod column gave a further shorting analysis time (5 min). These results indicated (1) surface-initiated ATRP constructed PIPAAm-brush structures on monolithic silica-rod surfaces and (2) PIPAAm-brush grafted monolithic silica-rod column prepared by ATRP was a promising tool for analyzing hydrophobic-bioactive compounds with a short analysis time.     

Melatonin prevents magnetic-field-induced neurite outgrowth in a subline of pheochromocytoma cells,PC12D

Exposure to extremely low frequency (ELF) magnetic fields (MFs) has been reported to affect several cellular processes, including cell growth and differentiation. Other research has demonstrated that the pineal gland and its hormone melatonin have a wide spectrum of effects in cells and organs and can exert modulatory actions on cell proliferation and cell differentiation. Since ELF electric and magnetic fields have been shown to influence pineal activity and melatonin synthesis and/or function, it has been suggested that some of the reported effects of ELF MFs could be a consequence of the direct action of these fields on the pineal gland and/or melatonin function. Possible interactions between MFs and melatonin effects are in an early stage of investigation. In this study, we have investigated the influence of melatonin on the in vitro response of a subline of pheochromocytoma cells, PC12D, to a MF. Cells were exposed to the combined action of a physiological concentration (10⁻¹⁰ M) of melatonin and a vertical, 50 Hz, 40 mG rms MF for 23 h. At the end of the treatment, the percentages of neurite-bearing cells were determined by microscopic examination and compared with those from samples treated with the field alone or with melatonin alone. MF exposure alone significantly increased the neurite outgrowth when compared with negative controls, supporting previous results by Blackman and coworkers; this effect was not observed when melatonin was present in the medium from the onset of the exposure. Although the mechanisms of action of melatonin and ELF MFs at the cellular level remain unknown, the present data suggest that physiological levels of melatonin can prevent PC12D cells from responding to the MF stimulus.     

Electrochemistry of organic,bioactive compounds and biopolymers

Monatshefte für Chemie - Chemical Monthly -     

An impedance QCM study on the partitioning of bioactive compounds in supported phospholipid bilayers

The interaction of two drugs of small molecular size, propranolol and tetracaine, and the membrane-perturbing peptide melittin with a phospholipid bilayer supported on a SiO2 surface was studied with the quartz crystal microbalance. All three bioactive compounds interacted with the lipid bilayer and changed its viscoelastic properties. Adsorbed mass of the compounds was analyzed with a viscoelastic model as a function of the concentration of the compounds in the aqueous phase, as well as the effect of the compounds on the bilayer viscoelasticity. The analysis was based on the interpretation of the impedance of the crystal, utilizing the 5th, 7th and 9th overtone of the fundamental 5 MHz resonance frequency.     

Optimization of CZE for analysis of phytochemical bioactive compounds

Advantages of CZE such as high efficiency, low cost, short analysis time, and easy implementation result in its wide applications for analysis of phytochemical bioactive compounds (e.g. flavonoids, alkaloids, terpenoids, phenolic acid, saponins, anthraquinones and coumarins). However, several aspects, including sample preparation, separation, and detection have significant effects on CZE analysis. Therefore, optimization of these procedures is necessary for development of the method. In this review, sample preparation such as extraction method and preconcentration, separation factors including buffer type, concentration and pH, additives, voltage and temperature, as well as detection, e.g. direct and indirect UV detection, LIF and MS were discussed for optimization of CZE analysis on phytochemical bioactive compounds. The optimized strategies were also reviewed.     

Lysophosphatidylcholine suppresses apoptosis and induces neurite outgrowth in PC12 cells through activation of phospholipase D2

Lysophosphatidylcholine (LPC) is a bioactive lipid generated by phospholipase A2-mediated hydrolysis of phosphatidylcholine. In the present study, we demonstrate that LPC stimulates phospholipase D2 (PLD2) activity in rat pheochromocytoma PC12 cells. Serum deprivation induced cell death of PC12 cells, as demonstrated by decreased viability, DNA fragmentation, and increased sub-G1 fraction of cell cycle. LPC treatment protected PC12 cells partially from the cell death and induced neurite outgrowth of the cells. Overexpression of PLD2 drastically enhanced the LPC-induced inhibition of apoptosis and neuritogenesis. Pretreatment of the cells with 1-butanol, a PLD inhibitor, completely abrogated the LPC-induced inhibition of apoptosis and neurite outgrowth in PC12 cells overexpressing PLD2. These results indicate that LPC possesses the neurotrophic effects, such as anti-apoptosis and neurite outgrowth, through activation of PLD2.     

Further development of reduced graphs for identifying bioactive compounds

Reduced graphs provide summary representations of chemical structures. Here, a variety of different types of reduced graphs are compared in similarity searches. The reduced graphs are found to give comparable performance to Daylight fingerprints in terms of the number of active compounds retrieved. However, no one type of reduced graph is found to be consistently superior across a variety of different data sets. Consequently, a representative set of reduced graphs was chosen and used together with Daylight fingerprints in data fusion experiments. The results show improved performance in 10 out of 11 data sets compared to using Daylight fingerprints alone. Finally, the potential of using reduced graphs to build SAR models is demonstrated using recursive partitioning. An SAR model consistent with a published model is found following just two splits in the decision tree.     

The complex role of the triphenylmethyl motif in anticancer compounds

Compounds incorporating the triphenylmethyl motif constitute an emerging family of potent anticancer agents. Although several small molecules containing this pharmacophore have now been identified, the mechanism of cell death induction for some of these compounds is unknown. In an effort to define their mechanism of action, and to distinguish subtypes within the group of compounds containing the triphenylmethyl moiety, we have created novel triphenylmethyl-containing small molecules and have evaluated them in a battery of biological assays. Here we show that several phosphonate and phosphonochloridates possessing the triphenylmethyl motif potently induce death of multiple cancer cell lines in culture. Further assays evaluating the ability to cause cell cycle arrest, inhibit tubulin polymerization, dissociate mitochondrial-bound hexokinase in cancer cells, and inhibit calcium-dependent potassium ion channels indicate that triphenylmethyl-containing compounds can be placed into at least four distinct categories, each with a different mechanism of action.     

Study of the interaction of structurally similar bioactive compounds by thin-layer chromatography

The interaction between steroids and cholesterol is studied by reversed-phase thin-layer chromatography (TLC) using TLC plates impregnated by cholesterol and methanol-water mixtures as the eluents. The R(M) values obtained are in linear correlation with the methanol concentration of the eluent. The slope obtained from the linear regression analysis, which is characteristic of the strength of interaction, is determined. Stepwise regression and principal component analysis are carried out to find a relationship between the physicochemical parameters of steroid drugs and the strength of the interaction, which is followed by nonlinear mapping and cluster analysis to visualize the obtained results. The results show that steric and electronic parameters of the steroid drugs have a significant effect on the strength of the interaction between these structurally similar molecules.     

Six-membered cyclic nitronates in the stereoselective synthesis of natural and bioactive compounds

In this report, the known strategies for the use of six-membered cyclic nitronates in directed organic synthesis are discussed.     

Green analytical methodologies for the discovery of bioactive compounds from marine sources

The application of green analytical chemistry in search of bioactive compounds is of paramount importance, leading to the development of environmentally friendly methodologies for their isolation. This work provides an up-to-date overview of the analytical methodologies based on a green perspective for the discovery of bioactive compounds from marine sources, namely to their extraction and structural characterization. Both the characteristics of marine bioactive compounds and the sustainable evaluation of their bioactivity are also addressed.