Effects of Red Sorghum-Derived Deoxyanthocyanidins and Their O-ß-D-Glucosides on E-Cadherin Promoter Activity in PC-3 Prostate Cancer Cells.

Although much less common than anthocyanins, 3-Deoxyanthocyanidins (3-DAs) and their glucosides can be found in cereals such as red sorghum. It is speculated that their bioavailability is higher than that of anthocyanins. Thus far, little is known regarding the therapeutic effects of 3-DAs and their O-ß-D-glucosides on cancer, including prostate cancer. Thus, we evaluated their potential to decrease cell viability, to modulate the activity of transcription factors such as NFκB, CREB, and SOX, and to regulate the expression of the gene CDH1, encoding E-Cadherin. We found that 4',7-dihydroxyflavylium chloride (P7) and the natural apigeninidin can reduce cell viability, whereas 4',7-dihydroxyflavylium chloride (P7) and 4'-hydroxy-7-O-ß-D-glucopyranosyloxyflavylium chloride (P3) increase the activities of NFkB, CREB, and SOX transcription factors, leading to the upregulation of CDH1 promoter activity in PC-3 prostate cancer cells. Thus, these compounds may contribute to the inhibition of the epithelial-to-mesenchymal transition in cancer cells and prevent the metastatic activity of more aggressive forms of androgen-resistant prostate cancer.

Genetic ablation of Immt induces a lethal disruption of the MICOS complex.

The mitochondrial contact site and cristae organizing system (MICOS) is important for crista junction formation and for maintaining inner mitochondrial membrane architecture. A key component of the MICOS complex is MIC60, which has been well studied in yeast and cell culture models. However, only one recent study has demonstrated the embryonic lethality of losing Immt (the gene encoding MIC60) expression. Tamoxifen-inducible ROSA-CreERT2-mediated deletion of Immt in adult mice disrupted the MICOS complex, increased mitochondria size, altered cristae morphology, and was lethal within 12 d. Pathologically, these mice displayed defective intestinal muscle function (paralytic ileus) culminating in dehydration. We also identified bone marrow (BM) hypocellularity in Immt-deleted mice, although BM transplants from wild-type mice did not improve survival. Altogether, this inducible mouse model demonstrates the importance of MIC60 in vivo, in both hematopoietic and non-hematopoietic tissues, and provides a valuable resource for future mechanistic investigations into the MICOS complex.

Simultaneous Writing and Erasing Using Probe Lithography Synchronized Erasing and Deposition (PLiSED).

Simultaneous writing and erasing of two and three molecules in one single step at the microscale using Polymeric Lithography Editor (PLE) probes is demonstrated. Simultaneous writing and erasing of three molecules was accomplished by rastering a nanoporous probe that was loaded with rhodamine B and fluorescein over a quinine-coated glass substrate. The solvated quinine molecules were erased and transported into the probe matrix, whereas both rhodamine and fluorescein molecules were simultaneously deposited and aligned with the path of the erased quinine on the substrate. The simultaneous writing and erasing of molecules is referred to as PLiSED. The writing and erasing speed can be easily tuned by adjusting the probe speed to as large as 10,000 µm2/s. The microscale patterns on the orders of square millimeter area were fabricated by erasing fluorescein with an efficiency (ηe) > 95% while simultaneously depositing rhodamine molecules at the erased spots. The roles of the probe porosity, transport medium, and kinetics of solvation for editing were also investigated─the presence of a transport medium at the probe-substrate interface is required for the transport of the molecules into and out of the probe. The physical and mechanical properties of the polymeric probes influenced molecular editing. Young's modulus values of the hydrated hydrogels composed of varying monomer/cross-linker ratios were estimated using atomic force microscopy. Probes with the highest observed erasing capacity were used for further experiments to investigate the effects of relative humidity and erasing time on editing. Careful control over experimental conditions provided high-quality editing of microscale patterns at high editing speed. Combining erasing and deposition of multiple molecules in one single step offers a unique opportunity to significantly improve the efficiency and the accuracy of lithographic editing at the microscale. PLiSED enables rapid on-site lithographic rectification and has considerable application values in high-quality lithography and solid surface modification.

Luteolin modulates gene expression related to steroidogenesis, apoptosis, and stress response in rat LC540 tumor Leydig cells.

In males, androgens are mainly produced by Leydig cells from the testis. A critical and highly regulated step of steroidogenesis involves the importation of cholesterol within the mitochondria by the steroidogenic acute regulatory (STAR) protein. During aging, STAR protein levels in Leydig cells gradually decrease, leading to a reduced entry of cholesterol into mitochondria and lower testosterone production. In addition to preserving its steroidogenic capacity, tumor Leydig cells can also be excellent models for evaluating the mechanisms of action of anticancer agents. In this study, we examined whether polyphenolics having structural similarities to luteolin could promote steroidogenic and cancer-related gene expressions within rat L540 tumor Leydig cells. In this cell model, luteolin activated Star expression and increased progesterone as well as testosterone productions. Interestingly, luteolin decreased gene expression related to cholesterol biosynthesis, possibly inhibiting membrane synthesis and cell proliferation. In addition, increased expression of genes such as Fas, Cdkn1a, Atp7b, and Tp53, as well as increased accumulation of cleaved caspase 3 and PARP, in response to luteolin treatment indicates that apoptosis is being activated. Luteolin also modulated the expression of genes involved in stress response, such as glutathione-S transferases Gsta1 and Gstt2, and the unfolded protein response. Thus, dietary luteolin may be effective in Leydig cell tumor chemoprevention and in maintaining steroidogenesis in aging males.

Analogs of Natural 3-Deoxyanthocyanins: O-Glucosides of the 4',7-Dihydroxyflavylium Ion and the Deep Influence of Glycosidation on Color.

3-Deoxyanthocyanidins and their O-ß-d-glucosides are natural pigments abundant in black sorghum. O-glycosidation can perturb the acid-base properties of the chromophore and lower its electron density with a large impact on the distribution of colored and colorless forms in aqueous solution. In this work, the influence of O-glycosidation on color is systematically studied from a series of 3-deoxyanthocyanin analogs. The pH- and light-dependent reversible reactions of 7-ß-d-glucopyranosyloxy-4'-hydroxyflavylium (P3) and 4'-ß-d-glucopyranosyloxy-7-hydroxyflavylium (P5) were completely characterized in mildly acidic solution and compared with the parent aglycone 4',7-dihydroxyflavylium ion and the O-methylethers of P3 and P5. Except P5, the chalcone forms of the pigments exhibit a high cis-trans isomerization barrier that allows a pseudo-equilibrium involving all species except the trans-chalcone. At equilibrium, only the flavylium cation and trans-chalcone are observed. With all pigments, the colored flavylium ion can be generated by irradiation of the trans-chalcone (photochromism). Glycosidation of C7-OH accelerates hydration and strongly slows down cis-trans isomerization with the pH dependence of the apparent isomerization rate constant shifting from a bell-shaped curve to a sigmoid. The color of P5 is much more stable than that of its regioisomer P3 in near-neutral conditions.

Quantification of three galloylglucoside flavour precursors by liquid chromatography tandem mass spectrometry in brandies aged in oak wood barrels.

Vanillin-(6'-O-galloyl)-ß-glucopyranoside (VGG), 3,4,5-trimethoxyphenyl-(6'-O-galloyl)-ß-glucopyranoside (TMPGG), and (6R,9R)-3-oxo-α-ionol-9-O-(6'-O-galloyl)-ß-glucopyranoside (macarangioside E) were identified as aroma precursors in oak wood. An LC-MS/MS method was developed and validated to quantify these three galloylglucoside compounds in brandies aged in oak barrels. The detection system consisted of a triple quadrupole mass analyser operating in multiple reaction monitoring (MRM) mode. For the first time, vanillin-ß-d-xylopyranoside (VX) was synthesised for use as an internal standard. The detection limits (48 µg L(-1) for VGG, 52 µg L(-1) for TMPGG, and 19 µg L(-1) for macarangioside E) were low enough to quantify these aroma precursors in spirits without any sample preparation.

Chemically synthesized glycosides of hydroxylated flavylium ions as suitable models of anthocyanins: binding to iron ions and human serum albumin, antioxidant activity in model gastric conditions.

Polyhydroxylated flavylium ions, such as 3',4',7-trihydroxyflavylium chloride (P1) and its more water-soluble 7-O-ß-d-glucopyranoside (P2), are readily accessible by chemical synthesis and suitable models of natural anthocyanins in terms of color and species distribution in aqueous solution. Owing to their catechol B-ring, they rapidly bind FeIII, weakly interact with FeII and promote its autoxidation to FeIII. Both pigments inhibit heme-induced lipid peroxidation in mildly acidic conditions (a model of postprandial oxidative stress in the stomach), the colorless (chalcone) forms being more potent than the colored forms. Finally, P1 and P2 are moderate ligands of human serum albumin (HSA), their likely carrier in the blood circulation, with chalcones having a higher affinity for HSA than the corresponding colored forms.

The impact of industrial processing on health-beneficial tomato microconstituents.

The effect of industrial processing was investigated on the stability of tomato carotenoids, phenolic compounds and ascorbic acid. A deep insight in the processed products allowed the quantification of caffeic acid hexosides, which are far more important contributors than the well-known chlorogenic acid, dicaffeoylquinic acids and quercetin oligosaccharides (new feruloyl, sinapoyl and syringoyl derivatives of quercetin apiosylrhamnosylglucoside). (E)-ß-Carotene and (E)-lycopene were also quantified along with different mono- and di-(Z)-isomers of lycopene which were tentatively assigned. Processing of fresh tomato into paste had an overall positive effect on the contents in phenolic compounds, no effect on lycopene and a slight and high detrimental effect on ß-carotene and ascorbic acid, respectively. The balance between the increase in tomato matrix extractability and microconstituent catabolism was further observed in two contrasted transformations of paste into sauce. Overall, the nutritional quality of tomato-processed products, except for ascorbic acid, is mainly preserved through manufacture.

Synthesis of hydroxycinnamic acid glucuronides and investigation of their affinity for human serum albumin.

Hydroxycinnamic acids (HCAs) are among the most abundant dietary polyphenols. Recent bioavailability studies have shown that HCAs enter the blood circulation mainly as glucuronides, which are thus most likely to express their potential health effects. In this work, an efficient synthesis of HCA O-arylglucuronides is developed. As for many xenobiotics, the resilience of HCA O-arylglucuronides in plasma and subsequent delivery to tissues could be governed by their binding to human serum albumin (HSA). Hence, the affinity of HCA O-arylglucuronides for HSA and its possible binding site were investigated by fluorescence spectroscopy. HCA O-arylglucuronides turn out to be moderate HSA ligands (K in the range 1-4 x 10(4) M(-1)) that bind HSA in sub-domain IIA, competitively or noncompetitively with other sub-domain IIA ligands such as dansylamide and the flavonol quercetin.

Chemical synthesis of hydroxycinnamic acid glucosides and evaluation of their ability to stabilize natural colors via anthocyanin copigmentation.

This work describes the chemical synthesis of O-aryl-beta-D-glucosides and 1-O-beta-D-glucosyl esters of hydroxycinnamic acids. In particular, O-aryl-beta-D-glucosides were efficiently prepared via a simple diastereoselective glycosylation procedure using phase transfer conditions. Despite the lability of its ester linkage, 1-O-beta-D-caffeoylglucose could also be obtained using a Lewis acid catalyzed glycosylation step and a set of protective groups that can be removed under neutral conditions. Hydroxycinnamic acid O-aryl-beta-D-glucosides were then quantitatively investigated for their affinity for the naturally occurring anthocyanin malvin (pigment). Formation of the pi-stacking molecular complexes (copigmentation) was characterized in terms of binding constants and enthalpy and entropy changes. The glucosyl moiety did not significantly alter these thermodynamic parameters, in line with a binding process solely involving the polyphenolic nuclei.

Antioxidant activity of olive phenols: mechanistic investigation and characterization of oxidation products by mass spectrometry.

In this work, the antioxidant activity of olive phenols is first characterized by their stoichiometries n(tot)(number of radicals trapped per antioxidant molecule) and their rate constants for the first H-atom abstraction k(1) by the stable radical DPPH. It appears that oleuropein, hydroxytyrosol and caffeic acid have the largest k(1) values, whereas dihydrocaffeic acid, an intestinal metabolite of caffeic acid, is the best antioxidant in terms of n(tot). For phenols with a catechol moiety n(tot) is higher than two, implying an antioxidant effect of their primarily formed oxidation products. A HPLC-MS analysis of the main products formed in the AAPH-induced oxidation of olive phenols reveals the presence of dimers and trimers. With hydroxytyrosol and dihydrocaffeic acid, oligomerization can take place with the addition of water molecules.The antioxidant activity of olive phenols is then evaluated by their ability to inhibit the AAPH-induced peroxidation of linoleic acid in SDS micelles. It is shown that olive phenols and quercetin act as retardants rather than chain breakers like alpha-tocopherol. From a detailed mechanistic investigation, it appears that the inhibition of lipid peroxidation by olive phenols can be satisfactorily interpreted by assuming that they essentially reduce the AAPH-derived initiating radicals. Overall, olive phenols prove to be efficient scavengers of hydrophilic peroxyl radicals with a long lasting antioxidant effect owing to the residual activity of some of their oxidation products.

Synthesis and surface-active properties of a new class of surfactants derived from D-gluconic acid.

Novel sugar-based surfactants were synthesized starting from D-gluconolactone. Three different functional groups were used to link the sugar moiety and the hydrophobic part. The physico-chemical properties for the use as adjuvant for pesticidal formulations of one of these compounds were evaluated and compared.