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PURPOSE: To investigate the impact of reduced injected doses on the quantitative and qualitative assessment of the amyloid PET tracers [18F]flutemetamol and [18F]florbetaben. METHODS: Cognitively impaired and unimpaired individuals (N = 250, 36% Aβ-positive) were included and injected with [18F]flutemetamol (N = 175) or [18F]florbetaben (N = 75). PET scans were acquired in list-mode (90-110 min post-injection) and reduced-dose images were simulated to generate images of 75, 50, 25, 12.5 and 5% of the original injected dose. Images were reconstructed using vendor-provided reconstruction tools and visually assessed for Aβ-pathology. SUVRs were calculated for a global cortical and three smaller regions using a cerebellar cortex reference tissue, and Centiloid was computed. Absolute and percentage differences in SUVR and CL were calculated between dose levels, and the ability to discriminate between Aβ- and Aβ + scans was evaluated using ROC analyses. Finally, intra-reader agreement between the reduced dose and 100% images was evaluated. RESULTS: At 5% injected dose, change in SUVR was 3.72% and 3.12%, with absolute change in Centiloid 3.35CL and 4.62CL, for [18F]flutemetamol and [18F]florbetaben, respectively. At 12.5% injected dose, percentage change in SUVR and absolute change in Centiloid were  80% for both tracers. CONCLUSION: This proof-of-concept study showed that for both [18F]flutemetamol and [18F]florbetaben, adequate quantitative and qualitative assessments can be obtained at 12.5% of the original injected dose. However, decisions to reduce the injected dose should be made considering the specific clinical or research circumstances.

To reveal the effect of sucrose concentration on the production of secondary metabolites, a metabolome and transcriptome joint analysis was carried out using callus induced from grape variety Mio Red cambial meristematic cells. We identified 559 metabolites—mainly flavonoids, phenolic acids, and stilbenoids—as differential content metabolites (fold change ≥2 or ≤0.5) in at least one pairwise comparison of treatments with 7.5, 15, or 30 g/L sucrose in the growing media for 15 or 30 days (d). Resveratrol, viniferin, and amurensin contents were highest at 15 d of subculture; piceid, ampelopsin, and pterostilbene had higher contents at 30 d. A transcriptome analysis identified 1310 and 498 (at 15 d) and 1696 and 2211 (at 30 d) differentially expressed genes (DEGs; log2(fold change) ≥ 1, p < 0.05) in 7.5 vs. 15 g/L and 15 vs. 30 g/L sucrose treatments, respectively. In phenylpropane and isoflavone pathways, DEGs encoding cinnamic acid 4-hydroxylase, chalcone synthase, chalcone isomerase, and flavanone 3-hydroxylase were more highly expressed at 15 d than at 30 d, while other DEGs showed different regulation patterns corresponding to sucrose concentrations and cultivation times. For all three sucrose concentrations, the stilbene synthase (STS) gene exhibited significantly higher expression at 15 vs. 30 d, while two resveratrol O-methyltransferase (ROMT) genes related to pterostilbene synthesis showed significantly higher expression at 30 vs. 15 d. In addition, a total of 481 DEGs were annotated as transcription factors in pairwise comparisons; an integrative analysis suggested MYB59, WRKY20, and MADS8 as potential regulators responding to sucrose levels in flavonoid and stilbene biosynthesis in grape callus. Our results provide valuable information for high-efficiency production of flavonoids and stilbenes using grape callus. [ABSTRACT FROM AUTHOR]

A straightforward procedure has been developed for the direct synthesis of stilbenes from benzylic chlorides and alcohols. The transformation employs a two-step one-pot protocol where the benzylic chloride is first subjected to a substitution with potassium cyanide in o -xylene. Without workup, the resulting arylacetonitrile is then reacted directly with the benzylic alcohol and potassium tert -butoxide to generate the stilbene framework. The condensation has been performed with a variety of commercially available benzylic chlorides and alcohols to afford substituted stilbenes as the pure E -isomers. A kinetic isotope effect of 5.2 has been measured for the overall transformation when comparing benzyl alcohol and α,α- d2-benzyl alcohol. The release of cyanide during the final elimination to stilbene has been confirmed by a picrate test. Thus, the potassium tert -butoxide-mediated elimination of cyanide is believed to proceed by an E1cB mechanism where the deprotonation reaction constitutes the rate-determining step. [ABSTRACT FROM AUTHOR]

UV-C exhibits efficient growth inhibition against a wide range of microorganisms and has an elicitor impact on the induction of resistance against pathogens in host plants, emerging as a promising alternative to fungicides. This study examined the defense elicitor effect of both low (0.05 W/cm2) and high (0.133 W/cm2) powered UV-C (275 nm) against Botrytis cinerea on grapevines. Gene expression, total stilbene content, and the quality of the berries were assessed in 'Kyoho' grapevines irradiated with UV-C. Low and high-powered UV-C reduced the in vitro growth of B. cinerea by 40–50% and lowered the in vivo infection and disease severity by 40–85% in the leaves. Lesion formation was reduced by 20–50% in berries treated with UV-C. The spores of B. cinerea did not infect the unwounded berries of 'Shine Muscat' and 'Kyoho' grape treated with UV-C. The augmented levels of total soluble solids, color values, and reduced titratable acidity improved the quality of the UV-C-irradiated 'Kyoho' berries compared to the control. The total stilbene content was four to five times higher with 37.48 µg g−1 fresh weight (FW) using low UV-powered UV-C and 43.11 µg g−1 FW using high UV-powered UV-C in 'Kyoho' berry skins treated with UV-C compared to the control (9.24 µg g−1 FW), with predominant levels of trans-resveratrol. The genes involved in stilbene synthesis, defense, and antioxidant activity were strongly upregulated in the leaves and berries of grapevines in response to the low and high UV-C treatments. The low and high UV-C treatments elicit the induction of resistances in grapes against B. cinerea and improve the quality of berries. Future research will be needed on other parameters before UV-C irradiation can be applied to inhibit the incidence of grey mold in vineyards. [ABSTRACT FROM AUTHOR]

Phenolic compounds are the main special metabolites of Cyperaceae species from phytochemical, pharmacological, and chemotaxonomical points of view. The present study focused on the isolation, structure determination, and pharmacological investigation of constituents from Carex praecox. Twenty-six compounds, including lignans, stilbenes, flavonoids, megastigmanes, chromenes, and phenylpropanoids, were identified from the methanol extract of the plant. Five of these compounds, namely, carexines A–E, are previously undescribed natural products. All compounds were isolated for the first time from C. praecox. The ACE-inhibitory activity of seven stilbenoid compounds was tested, and (–)-hopeaphenol proved to be the most active (IC50 7.7 ± 0.9 μM). The enzyme–kinetic studies revealed a mixed-type inhibition; therefore, domain-specific studies were also conducted. The in silico docking of (–)-hopeaphenol to the ACE affirmed some favorable interactions. In addition, the antiproliferative and antibacterial effects of some compounds were also evaluated. [ABSTRACT FROM AUTHOR]

Background: This study was conducted to assess the prospective association between dietary polyphenols intakes and risk of metabolic syndrome (MetS) and its components. Methods: Participants in this study (n = 4559) were selected from among the adults of the Tehran Lipid and Glucose Study (TLGS) with an average follow-up of 5.9 + 2.5 years. Biochemical and anthropometric variables were measured at baseline and follow-up examinations. A reliable and valid semi-quantitative food frequency questionnaire was used to evaluate dietary intakes. The incidence of MetS and its components in relation to polyphenols and its subclasses (phenolic acids, flavonoids, lignans, and stilbenes) was evaluated using multivariable Cox proportional hazard regression models. Results: Of the 4559 subjects who enrolled in the present study, 1765 were male aged 38.6 + 14.2 y and 2794 were female aged 35.9 + 11.7 y. The hazard ratios of MetS were 25% lower in Q2 (HR, 95% CI: 0.75, 0.64-0.88), 22% lower in Q3 (HR, 95% CI: 0.78, 0.65-0.94) and 24% lower in Q4 (HR, 95% CI: 0.76, 0.61-0.95) in comparison to Q1, whereas the results for subclasses of polyphenol were non-significant. The risk of high blood pressure (BP) reduced from quartiles 1 to 4 for phenolic acid (HR: 1.00, 0.88, 0.79, 0.80, Ptrend = 0.03). The risk of low high-density lipoprotein cholesterol (HDL-C) increased across quartiles of phenolic acid (HR: 1.00, 1.22, 1.07, 1.30, Ptrend = 0.02). Conclusion: This study highlights the potential protective role of total dietary polyphenols in the prevention of MetS. These findings could be the starting point of upcoming trials to illuminate the optimal level of polyphenols deriving from the intake of polyphenolrich diets to prevent MetS. [ABSTRACT FROM AUTHOR]

Wild grapevines are a rich source of polyphenolic compounds. Various environmental factors can influence these bioactive metabolites, contributing to stress mitigation and adaptation. The present study aimed to investigate the impact of prolonged drought stress on the accumulation of phytochemicals, antioxidants, and antimicrobial activity in the roots of the endangered Tunisian wild grapevine (Vitis vinifera subsp. sylvestris) "Tebaba" genotype. The results revealed that under prolonged drought stress, there was a significant increase in total phenolic compounds, total flavonoid content, and stilbenes, which showed a positive and significant correlation with the total antioxidant activity. Furthermore, the ethanolic extracts demonstrated an enhanced in vitro antibacterial effect against selected human pathogenic bacterial strains, including Staphylococcus aureus, Methicillin-resistant S. aureus, and Enterococcus faecalis. The minimum inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC) values, relative to prolonged drought stress, ranged from 125 to 250 µg/mL. The values of the ratio between MBC and the MIC showed that the activity of the root extract was bactericidal in all cases (MBC/MIC ≤ 2). This study highlights the potential of wild grapevine roots enriched with drought-inducible phenolic compounds, as a promising source of antimicrobial agents relevant to human health applications. [ABSTRACT FROM AUTHOR]

Introduction: Rhubarb is a traditional Chinese medicine (TCM) used to release heat and has cathartic effects. Official rhubarb in Taiwan Herbal Pharmacopeias 4th edition (THP 4th) and China Pharmacopeia 2020 (CP 2020) are the roots and rhizomes of Rheum palmatum L., Rheum tanguticum Maxim. ex Balf., and Rheum officinale Baill. However, the Rheum genus is a large genus with many different species, and owing to the similarity in appearance and taste with official rhubarb, there needs to be more clarity in the distinction between the species of rhubarb and their applications. Given the time-consuming and complicated extraction and chromatography methods outlined in pharmacopeias, we improved the qualitative analysis and quantitative analysis methods for rhubarb in the market. Hence, we applied our method to identify the species and quality of official and unofficial rhubarb. Method: We analyzed 21 rhubarb samples from the Taiwanese market using a proposed HPLC-based extraction and qualitative analysis employing eight markers: aloe-emodin, rhein, emodin, chrysophanol, physcion, rhapontigenin, rhaponticin, and resveratrol. Additionally, we developed a TLC method for the analysis of rhubarb. KEGG pathway analysis was used to clarify the phytochemical and pharmacological knowledge of official and unofficial rhubarb. Results: Rhein and rhapontigenin emerged as key markers to differentiate official and unofficial rhubarb. Rhapontigenin is abundant in unofficial rhubarb; however, rhein content was low. In contrast, their contents in official rhubarb were opposite to their contents in unofficial rhubarb. The TLC analysis used rhein and rhapontigenin to identify rhubarb in Taiwan's markets, whereas the KEGG pathway analysis revealed that anthraquinones and stilbenes affected different pathways. Discussion: Eight reference standards were used in this study to propose a quality control method for rhubarb in Taiwanese markets. We propose a rapid extraction method and quantitative analysis of rhubarb to differentiate between official and unofficial rhubarb. [ABSTRACT FROM AUTHOR]

In modern times, medicine is predominantly based on evidence-based practices, whereas in ancient times, indigenous people relied on plant-based medicines with factual evidence documented in ancient books or folklore that demonstrated their effectiveness against specific infections. Plants and microbes account for 70% of drugs approved by the USFDA (U.S. Food and Drug Administration). Stilbenes, polyphenolic compounds synthesized by plants under stress conditions, have garnered significant attention for their therapeutic potential, bridging ancient wisdom with modern healthcare. Resveratrol, the most studied stilbene, initially discovered in grapes, red wine, peanuts, and blueberries, exhibits diverse pharmacological properties, including cardiovascular protection, antioxidant effects, anticancer activity, and neuroprotection. Traditional remedies, documented in ancient texts like the Ayurvedic Charak Samhita, foreshadowed the medicinal properties of stilbenes long before their modern scientific validation. Today, stilbenes are integral to the booming wellness and health supplement market, with resveratrol alone projected to reach a market value of 90 million US$ by 2025. However, challenges in stilbene production persist due to limited natural sources and costly extraction methods. Bioprospecting efforts reveal promising candidates for stilbene production, particularly endophytic fungi, which demonstrate high-yield capabilities and genetic modifiability. However, the identification of optimal strains and fermentation processes remains a critical consideration. The current review emphasizes the knowledge of the medicinal properties of Stilbenes (i.e., cardiovascular, antioxidant, anticancer, anti-inflammatory, etc.) isolated from plant and microbial sources, while also discussing strategies for their commercial production and future research directions. This also includes examples of novel stilbenes compounds reported from plant and endophytic fungi. [ABSTRACT FROM AUTHOR]

Two new stilbenes, 5-methoxy-6-(4-methoxystyryl)-3-methylbenzofuran (1) and 5-methoxy-6-(4- hydroxystyryl)-3-methylbenzofuran (2), together with six known ones, bauhiniastatin D (3), gramideoxybenzoin B (4), gramistilbenoid A (5), gramistilbenoid B (6), gramniphenol H (7), and pterostilbene (8), were isolated from the whole plants of Arundina graminifolia. Their structures were established by their 1D, 2D NMR, and MS spectral data. Compounds 1 and 2 were tested for their anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) activity. The results revealed that compound 1 exhibited potential activity with IC50 of 17.4 μM for delta strain and 28.5 μM for Omicron BA.1 strain, compound 2 also showed potential activity with IC50 of 15.3 μM for delta strain and 22.6 μM for Omicron BA.1 strain, respectively. [ABSTRACT FROM AUTHOR]

The aim of this study was to establish an analytical method for the simultaneous detection of chloramphenicol, stilbenes, and resorcylic acid lactones. After enzymatic hydrolysis, pork samples were extracted by ethyl acetate. Two methods were used for purification: a C18 cartridge and immunoaffinity microextraction in a packed syringe. The samples were analyzed by UPLC–MS/MS on an Acquity UPLC® BEH C18 column with gradient elution. The methods were demonstrated to be suitable for the determination of chloramphenicol, stilbenes, and resorcylic acid lactones in pork. The SPE–UPLC–MS/MS had average recoveries of 42.4–97.1%. The intra-day and inter-day RSDs ranged from 6.1 to 16.9% and 3.7 to 18.4%, respectively. The IA–MPES–UPLC–MS/MS had average recoveries of 14.6–33.3%, and the intra-day and the inter-day RSDs ranged from 4.7 to 19.2% and 1.0 to 16.5%, respectively. Overall, the immunoaffinity microextraction in a packed syringe saves the organic reagent when balancing the C18 cartridge; thus, the dose of the organic reagent is less. However, the recovery of extraction by immunoaffinity microextraction in a packed syringe is less ideal. [ABSTRACT FROM AUTHOR]

Lignin, flavonoids, melatonin, and stilbenes are plant specialized metabolites with diverse physiological and biological functions, supporting plant growth and conferring stress resistance. Their biosynthesis requires O -methylations catalyzed by 5-hydroxyconiferaldehyde O -methyltransferase (CAldOMT; also called caffeic acid O -methyltransferase, COMT). CAldOMT was first known for its roles in syringyl (S) lignin biosynthesis in angiosperm cell walls and later found to be multifunctional. This enzyme also catalyzes O -methylations in flavonoid, melatonin, and stilbene biosynthetic pathways. Phylogenetic analysis indicated the convergent evolution of enzymes with OMT activities towards the monolignol biosynthetic pathway intermediates in some gymnosperm species that lack S-lignin and Selaginella moellendorffii , a lycophyte which produces S-lignin. Furthermore, neofunctionalization of CAldOMTs occurred repeatedly during evolution, generating unique O -methyltransferases (OMTs) with novel catalytic activities and/or accepting novel substrates, including lignans, 1,2,3-trihydroxybenzene, and phenylpropenes. This review summarizes multiple aspects of CAldOMTs and their related proteins in plant metabolism and discusses their evolution, molecular mechanism, and roles in biorefineries, agriculture, and synthetic biology. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION trans‐Resveratrol (TR) is a well‐known phytochemical compound with important biological properties. It can be recovered from agri‐food by‐products or wastes, such as vine shoots. Once recovered, its concentration should be measured, possibly in a green, non‐destructive, and efficient manner. With these premises, this work aimed to explore the feasibility of excitation‐emission fluorescence spectroscopy combined with chemometrics for the analysis of TR in raw extracts obtained from vine shoots. A total of 75 extracts were produced and analyzed by ultra‐performance liquid chromatography method with diode array detection (UPLC‐DAD) and spectrofluorimetry. Then, the feasibility of two calibration strategies for TR quantitation was assessed – a parallel factor analysis (PARAFAC)‐based calibration and the N‐way partial least squares (NPLS) regression.The extracts showed variable TR content, the excitation/emission maxima of which were at around 305/390 nm, respectively. The best PARAFAC‐based calibration allowed a root mean square error of prediction (RMSEP) of 22.57 mg L−1, and a relative prediction deviation (RPD) of 2.91 to be obtained but a large number of PARAFAC components should be considered to improve the predictions. The results of the NPLS regression were slightly better, with a RMSEP of 19.47 mg L−1, and an RPD of 3.33 in the best case.Fluorescence could be an alternative analytical technique to measure TR in complex samples. Chemometric tools allowed the identification of the TR signal in the fluorescence landscapes, which could be further used for its non‐destructive quantitation. The need for a more accurate criterion for optimal PARAFAC complexity emerged. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

With the aim of screening more bioactivity metabolites, in this study, two new stilbenes, 5-methoxy-6-(4- methoxystyryl)benzofuran (1) and 6-(4-methoxystyryl)benzofuran-5-ol (2) were isolated from the leaves and stems of Bletilla striata. Their structures were established by their 1D, 2D NMR, and MS spectral data. Interestingly, the anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) activity revealed that compound 1 exhibited potential anti-SARS-CoV-2 activity with IC50 of 15.2 μM for the delta strain and 22.8 μM for the omicron BA.1 strain; compound 2 also showed potential anti-SARS-CoV-2 activity with IC50 of 10.2 μM for the delta strain and 16.8 μM for the omicron BA.1 strain. These values are lower than that of a positive control (with IC50 of 1.2 μM for the delta strain and 3.4 μM for the omicron BA.1 strain). [ABSTRACT FROM AUTHOR]

Sulfur dioxide (SO2) is one of the most used additives in wine industry for its antioxidant and antimicrobial activity. However, due to health concerns, consumers’ demand of wines with either reduced or totally replaced SO2 has increased. This study aimed to assess the effect of partial and total replacement of SO2 with a vine-shoots extract rich in stilbenes in rosé (cv. Sangiovese) and red (cv. Negramaro) wines respectively. Color as well as phenolic, volatile, and sensory profiles of wines were evaluated at bottling and during storage.The results showed that the vine-shoots extract increased the levels of trans-resveratrol, catechin, and gallic acid in wines. Moreover, the positive correlation of procyanidin dimers in red wine suggested an increase of the polymerization reactions. The amount of added extract probably provided lower antimicrobial protection compared to SO2, as indicated by the higher levels of ethyl phenol. The decrease of individual anthocyanins and oxidation aldehydes observed in wines with SO2 replacement and the higher levels of caftaric acid in the rosé wine with the extract suggested a shift of the oxidative protection, with a lower protection towards anthocyanin degradation and higher protection towards carbonyl formation and oxidation of readily oxidizable phenolic acids.

Resveratrol (RSV) is a stilbenoid compound that shows anticancer activity in many cancer cells. Exosomes might affect carcinogenesis and the development of colorectal cancer by affecting communication between tumor cells in the tumor microenvironment via their cargo content miRNA. The aim of this study is to determine the effect of RSV on the expression of Dicer, Ago2, eIf2α, CD-9, CD-63, and exosomal miRNA levels in COLO320 and COLO741 colon cancer cell lines.

To reveal the effect of sucrose concentration on the production of secondary metabolites, a metabolome and transcriptome joint analysis was carried out using callus induced from grape variety Mio Red cambial meristematic cells. We identified 559 metabolites—mainly flavonoids, phenolic acids, and stilbenoids—as differential content metabolites (fold change ≥2 or ≤0.5) in at least one pairwise comparison of treatments with 7.5, 15, or 30 g/L sucrose in the growing media for 15 or 30 days (d). Resveratrol, viniferin, and amurensin contents were highest at 15 d of subculture; piceid, ampelopsin, and pterostilbene had higher contents at 30 d. A transcriptome analysis identified 1310 and 498 (at 15 d) and 1696 and 2211 (at 30 d) differentially expressed genes (DEGs; log2(fold change) ≥ 1, p < 0.05) in 7.5 vs. 15 g/L and 15 vs. 30 g/L sucrose treatments, respectively. In phenylpropane and isoflavone pathways, DEGs encoding cinnamic acid 4-hydroxylase, chalcone synthase, chalcone isomerase, and flavanone 3-hydroxylase were more highly expressed at 15 d than at 30 d, while other DEGs showed different regulation patterns corresponding to sucrose concentrations and cultivation times. For all three sucrose concentrations, the stilbene synthase (STS) gene exhibited significantly higher expression at 15 vs. 30 d, while two resveratrol O-methyltransferase (ROMT) genes related to pterostilbene synthesis showed significantly higher expression at 30 vs. 15 d. In addition, a total of 481 DEGs were annotated as transcription factors in pairwise comparisons; an integrative analysis suggested MYB59, WRKY20, and MADS8 as potential regulators responding to sucrose levels in flavonoid and stilbene biosynthesis in grape callus. Our results provide valuable information for high-efficiency production of flavonoids and stilbenes using grape callus.

Neurodegenerative disorders are characterized by mitochondrial dysfunction and subsequently oxidative stress, inflammation, and apoptosis that contribute to neuronal cytotoxicity and degeneration. Huntington's (HD), Alzheimer's (AD), and Parkinson's (PD) diseases are three of the major neurodegenerative diseases. To date, researchers have found various natural phytochemicals that could potentially be used to treat neurodegenerative diseases. Particularly, the application of natural phenolic compounds has gained significant traction in recent years, driven by their various biological activities and therapeutic efficacy in human health. Polyphenols, by modulating different cellular functions, play an important role in neuroprotection and can neutralize the effects of oxidative stress, inflammation, and apoptosis in animal models. This review focuses on the current state of knowledge on phenolic compounds, including phenolic acids, flavonoids, stilbenes, and coumarins, as well as their beneficial effects on human health. We further provide an overview of the therapeutic potential and mechanisms of action of natural dietary phenolics in curing neurodegenerative diseases in animal models. [ABSTRACT FROM AUTHOR]

Naturally occurring stilbenoids, such as the (E)-stilbenoid resveratrol and the (Z)-stilbenoid combretastatin A4, have been considered as promising lead compounds for the development of anticancer drugs. The antitumour properties of stilbenoids are known to be modulated by cytochrome P450 enzymes CYP1A1 and CYP1B1, which contribute to extrahepatic phase I xenobiotic and drug metabolism. Thirty-four methyl ether analogues of resveratrol were synthesised, and their anticancer properties were assessed, using the MTT cell proliferation assay on a panel of human breast cell lines. Breast tumour cell lines that express CYP1 were significantly more strongly affected by the resveratrol analogues than the cell lines that did not have CYP1 activity. Metabolism studies using isolated CYP1 enzymes provided further evidence that (E)-stilbenoids can be substrates for these enzymes. Structures of metabolic products were confirmed by comparison with synthetic standards and LC-MS co-elution studies. The most promising stilbenoid was (E)-4,3′,4′,5′-tetramethoxystilbene (DMU212). The compound itself showed low to moderate cytotoxicity, but upon CYP1-catalysed dealkylation, some highly cytotoxic metabolites were formed. Thus, DMU212 selectively affects proliferation of cells that express CYP1 enzymes. [ABSTRACT FROM AUTHOR]

The DBU‐catalyzed benzylation of 1H‐benzotriazole amides with methyl coumalate is demonstrated for the synthesis of stilbenes and biaryl derivatives. The transformation involves the base‐catalyzed Michael addition of methyl coumalate to the 6π‐electrocyclic ring opening decarboxylation aromatization. Furthermore, the novel 2‐phenylnaphthalene derivatives showed potent anti‐proliferative and anti‐invasive activities against H1299 cells. [ABSTRACT FROM AUTHOR]

Copper(I)-catalyzed azide-alkyne cycloaddition was employed to construct biscalixarene assemblies from the calix[4]arene dipropargyl ethers and 4,4′-bis-azidomethylated azobenzene or stilbene. Three bis(calixarenes) having the calix[4]arene cores linked to each other by pairs of (E)-azobenzene/stilbene units through four triazole groups were obtained as confirmed by NMR, HRMS and X-ray diffraction data. Nevertheless, the formation of larger macrocycles and polymeric/oligomeric products was found to be the major competing process that seriously limited the applicability of the one-step macrocyclization approach for the construction of photoresponsive biscalixarene assemblies linked by pairs of azobenzene/stilbene units. [ABSTRACT FROM AUTHOR]

The abnormal proliferation of Cutibacterium acnes is the main cause of acne vulgaris. Natural antibacterial plant extracts have gained great interest due to the efficacy and safety of their use in skin care products. Bletilla striata is a common externally used traditional Chinese medicine, and several of its isolated stilbenes were reported to exhibit good antibacterial activity. In this study, the antimicrobial activity of stilbenes from B. striata (BSS) against C. acnes and its potential effect on cell membrane were elucidated by determining the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), bacterial growth curve, adenosine triphosphate (ATP) levels, membrane potential (MP), and the expression of genes related to fatty acid biosynthesis in the cell membrane. In addition, the morphological changes in C. acnes by BSS were observed using transmission electron microscopy (TEM). Experimentally, we verified that BSS possessed significant antibacterial activity against C. acnes, with an MIC and MBC of 15.62 μg/mL and 62.5 μg/mL, respectively. The growth curve indicated that BSS at 2 MIC, MIC, 1/2 MIC, and 1/4 MIC concentrations inhibited the growth of C. acnes. TEM images demonstrated that BSS at an MIC concentration disrupted the morphological structure and cell membrane in C. acnes. Furthermore, the BSS at the 2 MIC, MIC, and 1/2 MIC concentrations caused a decrease in the intracellular ATP levels and the depolarization of the cell membrane as well as BSS at an MIC concentration inhibited the expression of fatty acid biosynthesis-associated genes. In conclusion, BSS could exert good antimicrobial activity by interfering with cell membrane in C. acnes, which have the potential to be developed as a natural antiacne additive. [ABSTRACT FROM AUTHOR]

Carex genus contains over 2000 species distributed all around the globe and used for their medicinal and food values. Owing to their traditional and medicinal properties the genus has gained due attention, especially in the last couple of decades which led to the identification of terpenoids, lignans, quinazolinones, phenolic acids, and phenylpropanoids as the major phytochemicals. Besides these several studies reported the therapeutic applications of the extracts and phytochemicals in different experimental conditions. The present review aims to present a comprehensive overview of the present standing of Carex genus that may promote further scientific exploration and their utilization.

Patients with early-onset Alzheimer's disease (EOAD) are commonly excluded from large-scale observational and therapeutic studies due to their young age, atypical presentation, or absence of pathogenic mutations. The goals of the Longitudinal EOAD Study (LEADS) are to (1) define the clinical, imaging, and fluid biomarker characteristics of EOAD; (2) develop sensitive cognitive and biomarker measures for future clinical and research use; and (3) establish a trial-ready network. LEADS will follow 400 amyloid beta (Aβ)-positive EOAD, 200 Aβ-negative EOnonAD that meet National Institute on Aging-Alzheimer's Association (NIA-AA) criteria for mild cognitive impairment (MCI) or AD dementia, and 100 age-matched controls. Participants will undergo clinical and cognitive assessments, magnetic resonance imaging (MRI), [18 F]Florbetaben and [18 F]Flortaucipir positron emission tomography (PET), lumbar puncture, and blood draw for DNA, RNA, plasma, serum and peripheral blood mononuclear cells, and post-mortem assessment. To develop more effective AD treatments, scientists need to understand the genetic, biological, and clinical processes involved in EOAD. LEADS will develop a public resource that will enable future planning and implementation of EOAD clinical trials.

[Display omitted] A new catalyst system for the Heck reaction consisting of PdCl 2 and 2,6-bis(1,2,4-diazaphosphol-1-yl)pyridine as a ligand is proposed. This system is efficient for the coupling of styrene with aryl bromides (K 3 PO 4 , DMA, 130 °C) at 0.1 mol% catalyst loading. [ABSTRACT FROM AUTHOR]

Phenolic compounds are the main special metabolites of Cyperaceae species from phytochemical, pharmacological, and chemotaxonomical points of view. The present study focused on the isolation, structure determination, and pharmacological investigation of constituents from Carex praecox. Twenty-six compounds, including lignans, stilbenes, flavonoids, megastigmanes, chromenes, and phenylpropanoids, were identified from the methanol extract of the plant. Five of these compounds, namely, carexines A–E, are previously undescribed natural products. All compounds were isolated for the first time from C. praecox. The ACE-inhibitory activity of seven stilbenoid compounds was tested, and (–)-hopeaphenol proved to be the most active (IC50 7.7 ± 0.9 μM). The enzyme–kinetic studies revealed a mixed-type inhibition; therefore, domain-specific studies were also conducted. The in silico docking of (–)-hopeaphenol to the ACE affirmed some favorable interactions. In addition, the antiproliferative and antibacterial effects of some compounds were also evaluated.

Phytoestrogens are non-steroid polyphenolic materials present in 300 plants. Regarding their structural similarities to estradiol, phytoestrogens attach to estrogen receptors and display anti-or pro-estrogenic activities. This review explored phytoestrogens' potential advantages and autophagy properties in light of their future application for disease management, highlighting how phytoestrogens could modulate autophagy. Research has examined the prospective benefits of phytoestrogens for the anticipation and management of various conditions, including signs of menopause, tumors, skin deterioration, osteoporosis, heart disease, neurodegenerative conditions, disorders of the immune system, and metabolic syndrome, owing to their therapeutic effects. As phytoestrogens can activate or inhibit autophagy, which has antioxidant, apoptotic, anti-mutagenic, anticancer, transcriptional, and genomic impacts on cancer and aging illnesses, phytoestrogens could influence diseases through the modulation of autophagy. The collaborative research on animal models, utilization of genetic techniques, and administration of pharmacolog¬ically active substances has indicated the possible therapeutic benefits of autophagy modulation in various illnesses. Further research is required to illustrate the pathways by which phytoestro¬gens modulate autophagy and the possible therapeutic effects on these diseases. [J Adv Vet Anim Res 2023; 10(2.000): 308-320]

Copper(I)-catalyzed azide-alkyne cycloaddition was employed to construct biscalixarene assemblies from the calix[4]arene dipropargyl ethers and 4,4′-bis-azidomethylated azobenzene or stilbene. Three bis(calixarenes) having the calix[4]arene cores linked to each other by pairs of (E)-azobenzene/stilbene units through four triazole groups were obtained as confirmed by NMR, HRMS and X-ray diffraction data. Nevertheless, the formation of larger macrocycles and polymeric/oligomeric products was found to be the major competing process that seriously limited the applicability of the one-step macrocyclization approach for the construction of photoresponsive biscalixarene assemblies linked by pairs of azobenzene/stilbene units.

Stilbenes are characterized by a vinyl group connecting two benzene rings to form the basic parent nucleus. Hydrogen atoms on different positions of the benzene rings can be substituted with hydroQxyl groups. These unique structural features confer anti-inflammatory, antibacterial, antiviral, antioxidant, anticancer, cardiovascular protective, and neuroprotective pharmacological effects upon these compounds. Numerous small molecule compounds have demonstrated these pharmacological activities in recent years, including Resveratrol, and Pterostilbene, etc. Tamoxifen and Raloxifene are FDA-approved commonly prescribed synthetic stilbene derivatives. The emphasis is on the potential of these small molecules and their structural derivatives as epigenetic regulators in various diseases. Stilbenes have been shown to modulate epigenetic marks, such as DNA methylation and histone modification, which can alter gene expression patterns and contribute to disease development. This review will discuss the mechanisms by which stilbenes regulate epigenetic marks in various diseases, as well as clinical trials, with a focus on the potential of small molecule and their derivatives such as Resveratrol, Pterostilbene, and Tamoxifen.

Oxidative stress has a significant impact on the occurrence of many chronic diseases. Antioxidants have ability to prevent, postpone or treat effects of free radicals. Resveratrol is a polyphenol from the class of stilbenes. The importance of this compound is determined by its numerous biological properties. The strong antioxidant potential is of special significance, because of the way it acts in the prevention and treatment of numerous chronic diseases. The antioxidant action of compound is direct, by inhibiting the production of reactive species, and indirect, by influencing the activity of numerous antioxidant enzymes. In the case of analyzing antioxidant potential by known methods, it was observed that RSV had a higher capacity than the standard used. Also, in vitro and in vivo studies demonstrate the activity of compound in prevention and treatment of neurodegenerative, cardiovascular and renal diseases. In addition, RSV is active in preeclampsia and infertility. An important aspect is the fact that polyphenol has the ability to reduce and counteract the adverse effects of some anticancer agents.

The control of oxidative stress with natural active substances could limit the development of numerous pathologies. Our objective was to study the antiradical effects of resveratrol (RSV), ε-viniferin (VNF), and vitisin B (VB) alone or in combination, and those of a standardized stilbene-enriched vine extract (SSVE). In the DPPH-, FRAP-, and NO-scavenging assays, RSV presented the highest activity with an IC50 of 81.92 ± 9.17, 13.36 ± 0.91, and 200.68 ± 15.40 µM, respectively. All binary combinations resulted in additive interactions in the DPPH- and NO-scavenging assays. In the FRAP assay, a synergic interaction for RSV + VNF, an additive for VNF + VB, and an antagonistic for RSV + VB were observed. The ternary combination of RSV + VNF + VB elicited an additive interaction in the DPPH assay and a synergic interaction in the FRAP- and NO-scavenging assays. There was no significant difference between the antioxidant activity of the SSVE and that of the combination of RSV + VNF. In conclusion, RSV presented the highest effects, followed by VNF and VB. The interactions revealed additive or synergistic effects, depending on the combination of the stilbenes and assay. [ABSTRACT FROM AUTHOR]

Three new stilbene dimers, paphiodianthins A-C (1–3), and nine known stilbenes, lignan and flavonoids (4–12) were isolated from the roots and leaves of Paphiopedilum dianthum (Orchidaceae). The structures of new compounds were elucidated from their NMR, HRESIMS and IR spectroscopic data. Cytotoxic activity of all isolated compounds was evaluated by in vitro MTT assay against two human cancer cell lines (MCF-7, Caco-2), doxorubicin-resistant and mitoxantrone-resistant MCF-7 sublines, as well as a normal cell line (NIH/3T3). Stilbenes 1, 3, 10 and 11 were strongly cytotoxic to both cancer cell lines with IC50 values ranging from 0.50 to 4.51 µM. Compounds 1, 10 and 11 were also active against chemotherapy-resistant MCF-7 sublines. [ABSTRACT FROM AUTHOR]

We report a selectivity‐switchable nickel hydride‐catalyzed methodology that enables the stereocontrolled semi‐reduction of internal alkynes to E‐ or Z‐alkenes under very mild conditions. The proposed transfer semi‐hydrogenation process involves the use of a dual nickel/photoredox catalytic system and triethylamine, not only as a sacrificial reductant, but also as a source of hydrogen atoms. Mechanistic studies revealed a pathway involving photo‐induced generation of nickel hydride, syn‐hydronickelation of alkyne, and alkenylnickel isomerization as key steps. Remarkably, mechanistic experiments indicate that the control of the stereoselectivity is not ensuing from a post‐reduction alkene photoisomerization under our conditions. Instead, we demonstrate that the stereoselectivity of the reaction is dependent on the rate of a final protonolysis step which can be tuned by adjusting the pKa of an alcohol additive. [ABSTRACT FROM AUTHOR]

With the increasing awareness of cardiovascular diseases and cancer prevention, the interest in resveratrol and its derivatives, i. e. hydroxylated stilbene compounds, as great antioxidants is growing day by day. The discovery of several other stilbene applications, especially in the treatment of numerous diseases, has further increased interest. Antidiabetic, anti‐inflammatory, antimicrobial, and anti‐neurodegenerative are just a few of the properties attributed to hydroxylated stilbene compounds. It is therefore not surprising that hydroxylated stilbenes are of great importance and frequently researched nowadays. In parallel, research in the field of flow chemistry has been increasing rapidly for years, as it offers many advantages in many different fields, including the synthesis of hydroxylated stilbenes. In this review article, a concise overview of stilbene compounds is given, as well as their properties and biological activity depending on the structure. In addition, various and common synthesis and production methods are described, with emphasis on application of flow chemistry in these processes. [ABSTRACT FROM AUTHOR]

The seeds of Paeonia clusii Stern subsp. clusii and Paeonia mascula (L.) Mill. subsp. mascula growing wild in Greece, though not previously investigated, has been studied as a source of bioactive stilbenoids and other phenolics. Their methanol extracts were analyzed using ultra high-performance liquid chromatography—high-resolution mass spectrometry (UHPLC-HRMS), and among the identified metabolites (62), 19 paeoniflorin's derivatives, 17 flavonoids and 12 stilbenes were detected. Moreover, through classic phytochemical separation procedures, twelve among them were isolated and fully spectrally determined as trans-resveratrol, trans-resveratrol-4′-O-β-D-glucopyranoside, cis-resveratrol-4′-O-β-D-glucopyranoside, trans-gnetin-H, trans-ε-viniferin, luteolin, luteolin-3′-O-β-D-glucopyranoside, luteolin-3′,4′-di-O-β-D-glucopyranoside, apigenin, hispidulin, paeoniflorin and benzoyl-paeoniflorin. All seed extracts were measured for their total phenolic content (TPC), appearing as a rich source (116.04 and 103.63 mg GAE/g extract, respectively), followed by free radical (DPPH) scavenging capacity (75.24% and 91.54% inhibition at the concentration of 200 μg/mL). The evaluation of tyrosinase inhibition for both extracts (61% and 70%, respectively) confirmed the potential for their future application in skin health care, comparable with other paeonies of Chinese origin, which are well-known as skin whitening and anti-aging promoters. [ABSTRACT FROM AUTHOR]

Abiotic factors such as water and nutrient availability can exert a dominant influence on the susceptibility of plants to various pathogens. Effects of abiotic environmental factors on phenolic compound concentrations in the plant tissue may represent one of the major underlying mechanisms, as these compounds are known to play a substantial role in plant resistance to pests. In particular, this applies to conifer trees, in which a large range of phenolic compounds are produced constitutively and/or induced by pathogen attack. We subjected Norway spruce saplings to water limitation and elevated nutrient supply over 2 years and subsequently controlled infection with the needle rust Chrysomyxa rhododendri (DC.) de Bary and analysed both constitutive and inducible phenolic compound concentrations in the needles as well as the degree of infection. Compared with the control group, both drought and fertilization profoundly modified the constitutive and pathogen-induced profiles of phenolic compounds, but had little impact on the total phenolic content. Fertilization predominantly affected the inducible phenolic response and led to higher infection rates by C. rhododendri. Drought stress, in contrast, mainly shaped the phenolic profiles in healthy plant parts and had no consequences on the plant susceptibility. The results show that specific abiotic effects on individual compounds seem to be decisive for the infection success of C. rhododendri , whereby the impaired induced response in saplings subjected to nutrient supplementation was most critical. Although drought effects were minor, they varied depending on the time and length of water limitation. The results indicate that prolonged drought periods in the future may not significantly alter the foliar defence of Norway spruce against C. rhododendri , but fertilization, often propagated to increase tree growth and forest productivity, can be counterproductive in areas with high pathogen pressure. Highlights Foliar phenolic profiles varied in response to water and nutrient availability. Following fertilization, phenolic accumulation in spruce was strongly impaired. Variations in specific compounds were decisive for the susceptibility to needle rust. [ABSTRACT FROM AUTHOR]

Stilbenes are phenolic compounds naturally synthesized as secondary metabolites by the shikimate pathway in plants. Research on them has increased in recent years due to their therapeutic potential as antioxidant, antimicrobial, anti-inflammatory, anticancer, cardioprotective and anti-obesity agents. Amongst them, resveratrol has attracted the most attention, although there are other natural and synthesized stilbenes with enhanced properties. However, stilbenes have some physicochemical and pharmacokinetic problems that need to be overcome before considering their applications. Human clinical evidence of their bioactivity is still controversial due to this fact and hence, exhaustive basis science on stilbenes is needed before applied science. This review gathers the main physicochemical and biological properties of natural stilbenes, establishes structure-activity relationships among them, emphasizing the current problems that limit their applications and presenting some promising approaches to overcome these issues: the encapsulation in different agents and the structural modification to obtain novel stilbenes with better features. The bioactivity of stilbenes should move from promising to evident. [ABSTRACT FROM AUTHOR]

The heartwood of the Swiss Stone Pine, Pinus cembra L., has been scarcely investigated for secondary metabolites for a long period of time. Considering age and relative simplicity of heartwood investigations dating back to the 1940s to 1960s, we conducted the first investigation of P. cembra heartwood by HPLC, using UHPLC-DAD-ESI-MSn and HPLC-DAD techniques in combination with isolation and NMR spectroscopy, with focus on stilbenes, bibenzyls and flavonoids. Analytical problems in the HPLC analysis of Pinus stilbenes and flavonoids on reversed stationary phases were also challenged, by comparing HPLC on pentafluorophenyl (PFP) and C18 stationary phases. Seven flavonoids (1, 2, 3, 7, 8, 11, 12), four stilbenes (4, 6, 10, 13), two bibenzyls (5, 9), three fatty acids (14, 16, 17) and one diterpenic acid (15) were detected in an ethanolic extract of Pinus cembra heartwood. HPLC comparison of reversed stationary phases in HPLC showed that the antifungal, antibacterial and chemosensitizing dihydropinosylvin monomethyl ether (9) and pinosylvin monomethyl ether (10) can be separated on PFP, but not on C18 material, when eluting with a screening gradient of 20–100% acetonitrile. Flavonoid separation showed additional benefits of combining analyses on different stationary phases, as flavonoids 7 and 8 could only be separated on one of two C18 stationary phases. Earlier phytochemical results for heartwood investigations were shown to be mostly correct, yet expandable. Substances 5 to 12 were found in alignment with these references, proving remarkable phytochemical analyses at the time. Evidence for the described presence of pinobanksin could not be found. Substances 1 to 4 and 13 have to our knowledge not yet been described for P. cembra. [ABSTRACT FROM AUTHOR]

Phytoalexins are naturally occurring molecules with antimicrobial activity deriving from the secondary metabolism of plants; they are synthesized in response to physical agents or stresses and phytopathogenic agents (fungi, bacteria and viruses), as well as numerous chemical compounds and biological control agents. Among these, grapevine phytoalexins, which belong to the chemical group of stilbenes, exhibit biocidal activity against a large number and variety of plant pathogens. It is important to investigate whether induction of stilbene phytoalexin production can serve to protect this plant against its pathogens. Quite a few chemical compounds, derivatives of phytohormones bio-elicitors as well as biocontrol agents, have been used to induce the synthesis of stilbene phytoalexins with the aim of conferring protection to grapevine against its main diseases (gray mold, downy mildew, powdery mildew and esca). This article reviews the experiments that have been carried out in this direction during the last 30 years and shows that the observed protective effects towards pathogens are generally linked to induction and priming of the grapevine phytoalexin response, confirming the interest in using, in a more general way, stimulation of the production of phytoalexins in plants as a basis for crop protection. [ABSTRACT FROM AUTHOR]

Four new stilbenes (1–4) and one new flavonoid (5), named cajanines D–H, together with three known stilbenes (6–8) were isolated from the leaves of Cajanus cajan (L.) Millsp. (pigeon pea). The structures of these compounds were elucidated unambiguously on the basis of IR, 1D, and 2D NMR, as well as HRESIMS data. Structurally, stilbenes 1–4 bore an isopentyl side chain, and further hydroxylation of compounds 1–3 generated a greater variety of structural forms. Compound 5 was a flavonoid owning an isopentyl side chain. Besides, antibacterial activity of the isolated compounds against Staphylococcus aureus, Bacillus cereus, and Escherichia coli was studied in vitro. Compounds 1–8 were endowed with profound antibacterial activity. Among them, the MIC values of compounds 4, 6, and 7 against S. aureus were 1.56, 0.78, and 0.78 µg/mL, respectively, among which 6 and 7 had better antibacterial activity than the positive control Vancomycin with the MIC values of 1.56 µg/mL. Additionally, the anti-SARS-CoV-2 main protease activity of all the isolated compounds was evaluated, and it was worth mentioning that the IC50 values of compounds 5–7 were 8.27, 4.65, and 8.30 µM, respectively, being comparable to the positive control Ebselen. Our findings may provide valuable guidance for the application of stilbenes as lead compounds in the future for the development of drugs with antibacterial or anti-COVID-19 activity. [ABSTRACT FROM AUTHOR]

Breast cancer is a leadingcause of cancer-related deaths in women globally, with triple-negative breast cancer (TNBC) being an aggressive subtype that lacks targeted therapies and is associated with a poor prognosis. Polyphenols, naturally occurring compounds in plants, have been investigated as a potential therapeutic strategy for TNBC. This review provides an overview of the anticancer effects of polyphenols in TNBC and their mechanisms of action. Several polyphenols, including resveratrol, quercetin, kaempferol, genistein, epigallocatechin-3-gallate, apigenin, fisetin, hesperetin and luteolin, have been shown to inhibit TNBC cell proliferation, induce cell cycle arrest, promote apoptosis, and suppress migration/invasion in preclinical models. The molecular mechanisms underlying their anticancer effects involve the modulation of several signalling pathways, such as PI3K/Akt, MAPK, STATT, and NF-κB pathways. Polyphenols also exhibit synergistic effects with chemotherapy drugs, making them promising candidates for combination therapy. The review also highlights clinical trials investigating the potential use of polyphenols, individually or in combination therapy, against breast cancer. This review deepens the under-standing of the mechanism of action of respective polyphenols and provides valuable insights into the potential use of polyphenols as a therapeutic strategy for TNBC, and lays the groundwork for future research in this area.