Controlling Crystal Morphology of Anisotropic Zeolites with Elemental Composition.

The morphology of zeolite crystals strongly affects their textural, catalytic, and mechanical attributes. However, controlling zeolite crystal morphology without using modifiers or structure-directing agents remains a challenging task because of our limited understanding of the relationships between zeolite crystal shape, crystallization mechanism, and composition of the starting synthesis mixture. In this study, we aimed at developing a general method for controlling the morphology of zeolites by assessing the impact of the Si/T molar ratio of the synthesis gel on the growth rate of zeolite crystals in various crystallographic directions and on the final crystal morphology of the UTL germanosilicate with a 2D system of intersecting 14- and 12-ring pores. Our results showed that flat UTL crystals progressively thicken with the Si/Ge molar ratio, demonstrating that Ge concentration controls the relative rate of crystal growth in the perpendicular direction to the pore system. The morphology of other zeolites and zeotypes with an anisotropic structure, including AFI (12R), IFR (12R), MWW (10-10R), and IWW (12-10-8R), can also be predicted based on their Si/T ratio, suggesting a systematic pattern across zeolite structures and in a wide range of zeolite framework elements. Combined, these findings introduce a facile and cost-efficient method for directly controlling crystal morphology of zeolites with anisotropic structures with a high potential for scale-up while providing further insights into the role of elemental composition in zeolite crystal growth.

Metabolism of Selected 2-Arylbenzofurans in a Colon In Vitro Model System.

2-arylbenzofurans represent a small group of bioactive compounds found in the plant family Moraceae. As it has not been investigated whether these substances are stable during passage through the gastrointestinal tract, their biological effects may be altered by the metabolism of intestinal microbiota or cells. The aim of the present study was to investigate and compare mulberrofuran Y (1), moracin C (2), and mulberrofuran G (3) in an in vitro model of human intestinal bacterial fermentation and in an epithelial model using the Caco-2 cell line. The analysis of compounds by LC-MS-Q-TOF showed sufficient stability in the fermentation model, with no bacterial metabolites detected. However, great differences in the quantity of permeation were observed in the permeability assay. Moreover, mulberrofuran Y (1) and moracin C (2) were observed to be transformed into polar metabolites by conjugation. Among the test compounds, mulberrofuran Y (1) was mostly stable and accumulated in endothelial cells (85.3%) compared with mulberrofuran G (3) and moracin C (2) (14% and 8.2%, respectively). Thus, only a small amount of mulberrofuran Y (1) was conjugated. Moracin C (2) and mulberrofuran G (3) were metabolized almost completely, with only traces of the unchanged molecule being found on the apical and cellular sides of the system. Only conjugates of mulberrofuran Y (1) and moracin C (2) were able to reach the basolateral side. Our results provide the basic description of bioavailability of these three compounds, which is a necessary characteristic for final evaluation of bio-efficacy.

Enhancing Bioavailability of Nutraceutically Used Resveratrol and Other Stilbenoids.

Stilbenoids are interesting natural compounds with pleiotropic in vitro and in vivo activity. Their well-documented biological properties include anti-inflammatory effects, anticancer effects, effects on longevity, and many others. Therefore, they are nowadays commonly found in foods and dietary supplements, and used as a part of treatment strategy in various types of diseases. Bioactivity of stilbenoids strongly depends on different types of factors such as dosage, food composition, and synergistic effects with other plant secondary metabolites such as polyphenols or vitamins. In this review, we summarize the existing in vitro, in vivo, and clinical data from published studies addressing the optimization of bioavailability of stilbenoids. Stilbenoids face low bioavailability due to their chemical structure. This can be improved by the use of novel drug delivery systems or enhancers, which are discussed in this review. Current in vitro and in vivo evidence suggests that both approaches are very promising and increase the absorption of the original substance by several times. However, data from more clinical trials are required.

Reverse ADOR: reconstruction of UTL zeolite from layered IPC-1P.

The assembly-disassembly-organisation-reassembly (ADOR) process has led to the discovery of numerous zeolite structures, albeit limited to materials with decreased pore size in relation to the parent germanosilicate zeolite. This limitation stems from the rapid decrease in d-spacing upon hydrolysis (disassembly). Nevertheless, we have artificially increased the d-spacing of layered IPC-1P by intercalating organic species. Furthermore, we have reconstructed double four rings (D4R) between layers, thus transforming IPC-1P back into the parent UTL zeolite. This reconstruction has provided not only germanosilicate but also a new, high-silica UTL zeolite (Si/Ge = 481). Therefore, our "reverse ADOR" opens up new synthetic routes towards promising extra-large-pore zeolite-based materials with new chemical compositions.

Metabolism of cis- and trans-Resveratrol and Dihydroresveratrol in an Intestinal Epithelial Model.

Trans-resveratrol, a well-known plant phenolic compound, has been intensively investigated due to its association with the so-called French paradox. However, despite its high pharmacological potential, trans-resveratrol has shown relatively low bioavailability. Trans-resveratrol is intensively metabolized in the intestine and liver, yielding metabolites that may be responsible for its high bioactivity. The aim of this study was to investigate and compare the metabolism of trans-resveratrol (tRes), cis-resveratrol (cRes) and dihydroresveratrol (dhRes) in an in vitro epithelial model using Caco-2 cell lines. Obtained metabolites of tRes, cRes and dhRes were analyzed by LC/MS Q-TOF, and significant differences in the metabolism of each compound were observed. The majority of tRes was transported unchanged through the Caco-2 cells, while cRes was mostly metabolized. The main metabolite of both cis- and trans-resveratrol observed as a result of colon microbial metabolism, dhRes, was metabolized almost completely, with only traces of the unchanged molecule being found. A sulphate conjugate was identified as the main metabolite of tRes in our model, while a glucuronide conjugate was the major metabolite of cRes and dhRes. Since metabolism of simple phenolics and polyphenols plays a crucial role in their bioavailability, detailed knowledge of their transformation is of high scientific value.

Prenylated Stilbenoids Affect Inflammation by Inhibiting the NF-κB/AP-1 Signaling Pathway and Cyclooxygenases and Lipoxygenase.

Stilbenoids are important components of foods (e.g., peanuts, grapes, various edible berries), beverages (wine, white tea), and medicinal plants. Many publications have described the anti-inflammatory potential of stilbenoids, including the widely known trans-resveratrol and its analogues. However, comparatively little information is available regarding the activity of their prenylated derivatives. One new prenylated stilbenoid (2) was isolated from Artocarpus altilis and characterized structurally based on 1D and 2D NMR analysis and HRMS. Three other prenylated stilbenoids were prepared synthetically (9-11). Their antiphlogistic potential was determined by testing them together with known natural prenylated stilbenoids from Macaranga siamensis and Artocarpus heterophyllus in both cell-free and cell assays. The inhibition of 5-lipoxygenase (5-LOX) was also shown by simulated molecular docking for the most active stilbenoids in order to elucidate the mode of interaction between these compounds and the enzyme. Their effects on the pro-inflammatory nuclear factor-κB (NF-κB) and the activator protein 1 (AP-1) signaling pathway were also analyzed. The THP1-XBlue-MD2-CD14 cell line was used as a model for determining their anti-inflammatory potential, and lipopolysaccharide (LPS) stimulation of Toll-like receptor 4 induced a signaling cascade leading to the activation of NF-κB/AP-1. The ability of prenylated stilbenoids to attenuate the production of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) was further evaluated using LPS-stimulated THP-1 macrophages.

Flavonoid Glycosides from Endemic Bulgarian Astragalus aitosensis (Ivanisch.).

Astragalus is a very interesting plant genus, well-known for its content of flavonoids, triterpenes and polysaccharides. Its secondary metabolites are described as biologically active compounds showing several activities, e.g., immunomodulating, antibacterial, antiviral and hepatoprotective. This inspired us to analyze the Bulgarian endemic A. aitosensis (Ivanisch.) to obtain deeper information about its phenolic components. We used extensive chromatographic separation of A. aitosensis extract to obtain seven phenolic compounds (1-7), which were identified using combined LC-MS and NMR spectral studies. The 1D and 2D NMR analyses and HR-MS allowed us to resolve the structures of known compounds 5-7 as isorhamnetin-3-O-robinobioside, isorhamnetin-3-O-(2,6-di-O-α-rhamno-pyranosyl-ß-galactopyranoside), and alangiflavoside, respectively, and further comparison of these spectral data with available literature helped us with structural analysis of newly described flavonoid glycosides 1-4. These were described in plant source for the first time.

Metabolism of Stilbenoids by Human Faecal Microbiota.

Stilbenoids are dietary phenolics with notable biological effects on humans. Epidemiological, clinical, and nutritional studies from recent years have confirmed the significant biological effects of stilbenoids, such as oxidative stress protection and the prevention of degenerative diseases, including cancer, cardiovascular diseases, and neurodegenerative diseases. Stilbenoids are intensively metabolically transformed by colon microbiota, and their corresponding metabolites might show different or stronger biological activity than their parent molecules. The aim of the present study was to determine the metabolism of six stilbenoids (resveratrol, oxyresveratrol, piceatannol, thunalbene, batatasin III, and pinostilbene), mediated by colon microbiota. Stilbenoids were fermented in an in vitro faecal fermentation system using fresh faeces from five different donors as an inoculum. The samples of metabolized stilbenoids were collected at 0, 2, 4, 8, 24, and 48 h. Significant differences in the microbial transformation among stilbene derivatives were observed by liquid chromatography mass spectrometry (LC/MS). Four stilbenoids (resveratrol, oxyresveratrol, piceatannol and thunalbene) were metabolically transformed by double bond reduction, dihydroxylation, and demethylation, while batatasin III and pinostilbene were stable under conditions simulating the colon environment. Strong inter-individual differences in speed, intensity, and pathways of metabolism were observed among the faecal samples obtained from the donors.

Effect of Selected Stilbenoids on Human Fecal Microbiota.

Dietary phenolics or polyphenols are mostly metabolized by the human gut microbiota. These metabolites appear to confer the beneficial health effects attributed to phenolics. Microbial composition affects the type of metabolites produced. Reciprocally, phenolics modulate microbial composition. Understanding this relationship could be used to positively impact health by phenolic supplementation and thus create favorable colonic conditions. This study explored the effect of six stilbenoids (batatasin III, oxyresveratrol, piceatannol, pinostilbene, resveratrol, thunalbene) on the gut microbiota composition. Stilbenoids were anaerobically fermented with fecal bacteria from four donors, samples were collected at 0 and 24 h, and effects on the microbiota were assessed by 16S rRNA gene sequencing. Statistical tests identified affected microbes at three taxonomic levels. Observed microbial composition modulation by stilbenoids included a decrease in the Firmicutes to Bacteroidetes ratio, a decrease in the relative abundance of strains from the genus Clostridium, and effects on the family Lachnospiraceae. A frequently observed effect was a further decrease of the relative abundance when compared to the control. An opposite effect to the control was observed for Faecalibacterium prausnitzii, whose relative abundance increased. Observed effects were more frequently attributed to resveratrol and piceatannol, followed by thunalbene and batatasin III.

Parallel in vitro and in silico investigations into anti-inflammatory effects of non-prenylated stilbenoids.

Stilbenoids represent a large group of bioactive compounds, which occur in food and medicinal plants. Twenty-five stilbenoids were screened in vitro for their ability to inhibit COX-1, COX-2 and 5-LOX. Piceatannol and pinostilbene showed activity comparable to the zileuton and ibuprofen, respectively. The anti-inflammatory potential of stilbenoids was further evaluated using THP-1 human monocytic leukemia cell line. Tests of the cytotoxicity on the THP-1 and HCT116 cell lines showed very low toxic effects. The tested stilbenoids were evaluated for their ability to attenuate the LPS-stimulated activation of NF-κB/AP-1. Most of the tested substances reduced the activity of NF-κB/AP-1 and later attenuated the expression of TNF-α. The effects of selected stilbenoids were further investigated on inflammatory signaling pathways. Non-prenylated stilbenoids regulated attenuation of NF-ĸB/AP-1 activity upstream by inhibiting the phosphorylation of MAPKs. A docking study used to in silico analyze the tested compounds confirmed their interaction with NF-ĸB, COX-2 and 5-LOX.