Trans-resveratrol (TR) is the biological active isomer of resveratrol and the one responsible for therapeutic effects; both molecules are non-flavonoid phenolics of the stilbenes class found mainly ...in berries and red grapes. TR biological properties lie in modulation of various enzymatic classes. It is a promising candidate to novel drugs due its applications in pharmaceutical and cosmetic industries, such as anticarcinogenic, antidiabetic, antiacne, antioxidant, anti-inflammatory, neuroprotective, and photoprotector agent. It has effects on bone metabolism, gastrointestinal tract, eyes, kidneys, and in obesity treatment as well. Nevertheless, its low solubility in water and other polar solvents may be a hindrance to its therapeutic effects. Various strategies been developed to overcome these issues, such as the drug delivery systems. The present study performed a research about methods to identify TR and RESV in several samples (raw materials, wines, food supplements, drug delivery systems, and blood plasma). Most of the studies tend to analyze TR and RESV by high performance liquid chromatography (HPLC) coupled with different detectors, even so, there are reports of the use of capillary electrophoresis, electron spin resonance, gas chromatography, near-infrared luminescence, UV-Vis spectrophotometer, and vibrational spectrophotometry, for this purpose. Thus, the review evaluates the biological activity of TR and demonstrates the currently used analytical methods for its quantification in different matrices.
Alzheimer’s disease (AD) is a neurodegenerative disease associated with amyloid-β (Aβ) deposition, leading to neurotoxicity (oxidative stress and neuroinflammation) and gut microbiota imbalance. ...Resveratrol (Res) has neuroprotective properties, but its bioavailability in vivo is very low. Herein, we developed a small Res-selenium-peptide nanocomposite to enable the application of Res for eliminating Aβ aggregate-induced neurotoxicity and mitigating gut microbiota disorder in aluminum chloride (AlCl3) and d-galactose(d-gal)-induced AD model mice. Res functional selenium nanoparticles (Res@SeNPs) (8 ± 0.34 nm) were prepared first, after which the surface of Res@SeNPs was decorated with a blood–brain barrier transport peptide (TGN peptide) to generate Res-selenium-peptide nanocomposites (TGN-Res@SeNPs) (14 ± 0.12 nm). Oral administration of TGN-Res@SeNPs improves cognitive disorder through (1) interacting with Aβ and decreasing Aβ aggregation, effectively inhibiting Aβ deposition in the hippocampus; (2) decreasing Aβ-induced reactive oxygen species (ROS) and increasing activity of antioxidation enzymes in PC12 cells and in vivo; (3) down-regulating Aβ-induced neuroinflammation via the nuclear factor kappa B/mitogen-activated protein kinase/Akt signal pathway in BV-2 cells and in vivo; and (4) alleviating gut microbiota disorder, particularly with respect to oxidative stress and inflammatory-related bacteria such as Alistipes, Helicobacter, Rikenella, Desulfovibrio, and Faecalibaculum. Thus, we anticipate that Res-selenium-peptide nanocomposites will offer a new potential strategy for the treatment of AD.
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Resveratrol was shown to exert anti-inflammatory effects in experimental models of psoriasis. Several natural oligomers of resveratrol have been extracted from plants. We investigated ...the antipsoriatic activity of topical administration of resveratrol oligomers and explored the effect of the number of resveratrol subunits on skin absorption to establish the structure-permeation relationship (SPR). Three oligomers, ε-viniferin (dimer), ampelopsin C (trimer) and vitisin A (tetramer), extracted from Vitis thunbergii root were compared to the resveratrol glycoside polydatin. Delivery to porcine skin was assessed in vitro using the Franz cell. Keratinocytes activated with imiquimod (IMQ) were utilized to evaluate cytokine/chemokine inhibition. Topical application of resveratrol and oligomers was characterized in vivo by assessing cutaneous absorption, skin physiology, proinflammatory mediator expression, and histopathology in IMQ-treated mice. Skin deposition decreased as the molecular size and lipophilicity of the permeants increased. Resveratrol exhibited highest absorption, followed by ε-viniferin. The monomers resveratrol and polydatin exhibited higher flux across skin than the larger oligomers. In silico modeling revealed the permeants that strongly interacted with stratum corneum (SC) lipids exhibited lower transport to viable skin and the receptor compartment. In vitro, resveratrol and its derivatives had comparable ability to inhibit IMQ-induced IL-1β, IL-6, and CXCL8 secretion in activated keratinocytes. In vivo, topically applied ε-viniferin accumulated at higher levels than resveratrol (0.067 versus 0.029 nmol/mg) in psoriasis-like mouse skin with impaired barrier capacity. Topical ε-viniferin alleviated psoriasiform symptoms and reduced IL-23 secretion (by 58% vs. 37%) more effectively than resveratrol. ε-Viniferin has potential as an anti-inflammatory agent to prevent or treat psoriasis.
-resveratrol (RSV) is a non-flavonoid polyphenol (stilbene) with numerous biological activities, such as anti-tumor activities. However, RSV is rapidly metabolized, which limits its therapeutic use. ...The availability of RSV analogues with similar activities for use in vivo is therefore a major challenge. For this purpose, several isomeric analogues of RSV, aza-stilbenes (AZA-ST 1a-g), were synthesized, and their toxicities were characterized and compared to those of RSV on murine N2a neuronal cells using especially flow cytometric methods. All AZA-ST 1a-g have an inhibitory concentration 50 (IC50) between 11.3 and 25 µM when determined by the crystal violet assay, while that of RSV is 14.5 µM. This led to the characterization of AZA-ST 1a-g-induced cell death, compared to RSV, using three concentrations encompassing the IC50s (6.25, 12.5 and 25 µM). For AZA-ST 1a-g and RSV, an increase in plasma membrane permeability to propidium iodide was observed, and the proportion of cells with depolarized mitochondria measured with DiOC
(3) was increased. An overproduction of reactive oxygen species (ROS) was also observed on whole cells and at the mitochondrial level using dihydroethidium and MitoSox Red, respectively. However, only RSV induced a mode of cell death by apoptosis associated with a marked increase in the proportion of cells with condensed and/or fragmented nuclei (12.5 µM: 22 ± 9%; 25 µM: 80 ± 10%) identified after staining with Hoechst 33342 and which are characteristic of apoptotic cells. With AZA-ST, a slight but significant increase in the percentage of apoptotic cells was only detected with AZA-ST 1b (25 µM: 17 ± 1%) and AZA-ST 1d (25 µM: 26 ± 4%). Furthermore, only RSV induced significant cell cycle modifications associated with an increase in the percentage of cells in the S phase. Thus, AZA-ST 1a-g-induced cell death is characterized by an alteration of the plasma membrane, an induction of mitochondrial depolarization (loss of ΔΨm), and an overproduction of ROS, which may or may not result in a weak induction of apoptosis without modification of the distribution of the cells in the different phases of the cell cycle.
A synthetic pathway to a novel 4-aryl-3,4-dihydro-2H-1,4-benzoxazine scaffold was developed and a series of compounds based on the scaffold were synthesised as potential anticancer agents. The ...4-aryl-substituted compounds were prepared via Buchwald–Hartwig cross-coupling between substituted bromobenzenes and various 1,4-benzoxazines, which in turn were generated from a cascade hydrogenation and reductive amination one-pot reaction. These analogues exhibited moderate to good potency against various cancer cell lines. Structure–activity relationship analysis indicated that the inclusion of hydroxyl groups on ring A and ring B was beneficial to biological activity, while having a para-amino group on ring C significantly enhanced potency. Molecule 14f displayed the most potent anticancer activity (ICsub.50 = 7.84–16.2 µM against PC-3, NHDF, MDA-MB-231, MIA PaCa-2, and U-87 MG cancer cell lines), indicating its potential as a lead compound for further structural optimisation. All the synthesised compounds were fully characterised with NMR, HMRS, and IR. The novel benzoxazine scaffold described in this study holds promise and deserves further in-depth studies.
Paeonia suffruticosa Andr. has been widely used in traditional Chinese medicine as an anti-tumour, anti-oxidant, anti-inflammatory and neuroprotective agent. Resveratrol oligomers are the main ...components of the seed coat extracts of Paeonia suffruticosa (PSCE) and have DPPH free radical scavenging and β-secretase inhibitory activity. However, studies of its effect on ameliorating cognitive deficits are limited, and analyses of the underlying mechanisms are insufficient.
This study aimed to investigate the cholinesterase inhibitory activities of resveratrol oligomers from P. suffruticosa in vitro and their effects on diminishing the oxygen-glucose deprivation/reoxygenation (OGD/R) -induced cytotoxicity in PC12 cells and scopolamine-induced cognitive deficits in mice. Moreover, the underlying mechanisms were further explored.
In vitro, the inhibitory effects of PSCE and its 10 stilbenes on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were evaluated using the Ellman's assay, and its protective effects on normal and OGD/R-injured PC12 cells were evaluated using the MTT assay. For the in vivo assay, C57BL/6 mice were orally administered with PSCE at doses of 150 and 600 mg/kg for 28 days, and injected with scopolamine (1.5 mg/kg) to induce cognitive deficits. The memory behaviours were evaluated using the novel object recognition, Morris water maze and inhibitory avoidance test. Levels of various biochemical markers were also examined, including AChE, choline acetyltransferase (ChAT), acetylcholine (ACh), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) in the mouse brain and interleukin-1β (IL-1β), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), interleukin-4 (IL-4) in serum.
PSCE and its 10 stilbenes display good inhibition of AChE and BuChE activities and significantly increase the viability of normal and OGD/R-injured PC12 cells. PSCE improves the cognitive performance of scopolamine-treated mice in behavioural tests. Meanwhile, PSCE increases AChE, ChAT, SOD, and CAT activities and ACh, GSH, IL-4 levels, and decreases IL-1β, IL-6, TNF-α levels in the model animals.
Resveratrol oligomers from P. suffruticosa show neuroprotective effect in vitro and in vivo by regulating cholinergic, antioxidant and anti-inflammatory pathways, may have promising application in the treatment of Alzheimer’s disease.
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•Resveratrol oligomers from P. suffruticosa seed coats demonstrate inhibition on AChE and BuChE in vitro.•Resveratrol oligomers improve PC12 cell viability and protect it from oxygen-glucose deprivation/reoxygenation injury.•Resveratrol oligomers counteract cognitive deficits in object recognition, water maze and inhibitory avoidance test.•Resveratrol oligomers ameliorate cholinergic and oxidative damage in mice brain, and inflammation in serum.
An efficient method of accessing new CFsub.3-containing spiro-indene-proline derivatives has been developed based on a Cp*Rh(III)-catalyzed tandem C-H activation/3+2–annulation reaction of ...5-aryl-2-(trifluoromethyl)-3,4-dihydro-2H-pyrrole-2-carboxylates with alkynes. An important feature of this spiro annulation process is the feasibility of dehydroproline moiety to act as a directing group in the selective activation of the aromatic C-H bond.
3,4-Bisfurazan and its N-oxide Khakhalev, Artem V; Anisimov, Aleksei Ð; Sheremetev, Aleksei B
Chemistry of heterocyclic compounds (New York, N.Y. 1965),
05/2022, Volume:
58, Issue:
4-5
Journal Article
Peer reviewed
The conditions for bromination of the methyl groups of dimethylglyoxime were found, and the resulting product, a 1,4-dioxane solvate of bis(bromomethyl)glyoxime, was used as a precursor for ...heterocyclizations involving cyclodehydration or oxidative cyclization of the oxime groups leading to the formation of furazan and furoxan rings, respectively.
Aquaporins (AQPs), membrane proteins responsible for facilitating water transport, found in plant membrane vesicles (MV), have been related to the functionality and stability of MV. We focused on ...AQPs obtained from broccoli, as they show potential for biotechnological applications. To gain further insight into the role of AQPs in MV, we describe the heterologous overexpression of two broccoli AQPs (BoPIP1;2 and BoPIP2;2) in Pichia pastoris, resulting in their purification with high yield (0.14 and 0.99 mg per gram cells for BoPIP1;2 and BoPIP2;2). We reconstituted AQPs in liposomes to study their functionality, and the size of proteoliposomes did not change concerning liposomes. BoPIP2;2 facilitated water transport, which was preserved for seven days at 4 °C and at room temperature but not at 37 °C. BoPIP2;2 was incorporated into liposomes to encapsulate a resveratrol extract, resulting in increased entrapment efficiency (EE) compared to conventional liposomes. Molecular docking was utilized to identify binding sites in PIP2s for resveratrol, highlighting the role of aquaporins in the improved EE. Moreover, interactions between plant AQP and human integrin were shown, which may increase internalization by the human target cells. Our results suggest AQP-based alternative encapsulation systems can be used in specifically targeted biotechnological applications.
Hypoxia not only plays a critical role in multiple disease conditions; it also influences the growth and development of cells, tissues and organs. To identify novel hypoxia-related mechanisms ...involved in cell and tissue growth, studying a precise hypoxia-sensitive time window can be an effective approach. Drosophila melanogaster has been a useful model organism for studying a variety of conditions, and we focused in this study on the life cycle stages of Drosophila to investigate their hypoxia sensitivity. When normoxia-grown flies were treated with 4% Osub.2 at the pupa stage for 3, 2 and 1 day/s, the eclosion rates were 6.1%, 66.7% and 96.4%, respectively, and, when 4% Osub.2 was kept for the whole pupa stage, this regimen was lethal. Surprisingly, when our hypoxia-adapted flies who normally live in 4% Osub.2 were treated with 4% Osub.2 at the pupa stage, no fly eclosed. Within the pupa stage, the pupae at 2 and 3 days after pupae formation (APF), when treated for 2 days, demonstrated 12.5 ± 8.5% and 23.6 ± 1.6% eclosion, respectively, but this was completely lethal when treated for 3 days. We conclude that pupae, at 2 days APF and for a duration of a minimum of 2 days, were the most sensitive to hypoxia. Our data from our hypoxia-adapted flies clearly indicate that epigenetic factors play a critical role in pupa-stage hypoxia sensitivity.
