Stilbene Resveratrol Research Articles

Phytochemicals and Nanotechnology: A Powerful Combination against Breast Cancer.

Considerable advancements have been made in breast cancer therapeutics in the past few decades. However, the advent of chemo-resistance and adverse drug reactions coupled with tumor metastasis and recurrence posed a serious threat to combat this lethal disease. Novel anti-cancer agents, as well as new therapeutic strategies, are needed to complement conventional breast cancer therapies. The quest for developing novel anti-cancer drugs caused an upsurge in exploring and harnessing natural compounds, especially phytochemicals. Various research groups have explored and documented the anti-cancer potential of wide variety of phytochemical groups including flavonoids (curcumin, kaempferol, myricetin, quercetin, naringenin, apigenin, genistein epigallocatechin gallate), stilbenes (resveratrol), carotenoids (crocin, lycopene, lutein), and anthraquinone (Emodin). However, low chemical stability, poor water solubility, and short systemic half-life impede their clinical utility. The implication of nano-technological approaches to decode the pharmacokinetic challenges associated with phytochemical usage, as well as selective drug targeting, have markedly enhanced the pre-clinical anti-cancer activity, thus aiding in their clinical translation. This review documented the recent advances in utilizing phytochemicals for breast cancer prevention and lipidbased nanotechnological approaches for circumventing their pharmacokinetic concerns to enhance their systemic availability, cytotoxicity, and targeted delivery against breast cancer alone as well as in combination with conventional therapeutic agents.

Prenylation of aromatic amino acids and plant phenolics by an aromatic prenyltransferase from Rasamsonia emersonii

Dimethylallyl tryptophan synthases (DMATSs) are aromatic prenyltransferases that catalyze the transfer of a prenyl moiety from a donor to an aromatic acceptor during the biosynthesis of microbial secondary metabolites. Due to their broad substrate scope, DMATSs are anticipated as biotechnological tools for producing bioactive prenylated aromatic compounds. Our study explored the substrate scope and product profile of a recombinant RePT, a novel DMATS from the thermophilic fungus Rasamsonia emersonii. Among a variety of aromatic substrates, RePT showed the highest substrate conversion for l-tryptophan and l-tyrosine (> 90%), yielding two mono-prenylated products in both cases. Nine phenolics from diverse phenolic subclasses were notably converted (> 10%), of which the stilbenes oxyresveratrol, piceatannol, pinostilbene, and resveratrol were the best acceptors (37–55% conversion). The position of prenylation was determined using NMR spectroscopy or annotated using MS2 fragmentation patterns, demonstrating that RePT mainly catalyzed mono-O-prenylation on the hydroxylated aromatic substrates. On l-tryptophan, a non-hydroxylated substrate, it preferentially catalyzed C7 prenylation with reverse N1 prenylation as a secondary reaction. Moreover, RePT also possessed substrate-dependent organic solvent tolerance in the presence of 20% (v/v) methanol or DMSO, where a significant conversion (> 90%) was maintained. Our study demonstrates the potential of RePT as a biocatalyst for the production of bioactive prenylated aromatic amino acids, stilbenes, and various phenolic compounds.Key points• RePT catalyzes prenylation of diverse aromatic substrates.• RePT enables O-prenylation of phenolics, especially stilbenes.• The novel RePT remains active in 20% methanol or DMSO.Graphical abstract

The effect of maltodextrin edible coating containing pyracantha extract and potassium nano-carbonate on secondary metabolites, antioxidant capacity and microbiological properties of grape during cold storage

This study aimed to investigate the postharvest application of edible coating of maltodextrin containing potassium nanoparticles (KNPs; 0–2%) and pyracantha extract (PE; 0–1.5 %) on the maintenance of phenolic compounds, antioxidant capacity and microbial properties of ‘Rishbaba’ grape during 60 days at −1 °C using response surface methodology and central composite design. The results showed that the applied coating on Rishbaba grape maintained total phenol, total flavonoids, total anthocyanin, stilbenes (resveratrol and viniferin) and catechin. That also caused higher antioxidant capacity and lower mold and yeast growth in grape during the storage time. Finally, the best cold storage conditions of ‘Rishbaba’ grape were determined by using the edible maltodextrin coating containing 2 % KNPs and 1.5 % of PE for 34 days with a desirability of 0.728 in terms of investigated Characteristics. The optimized sample has the amount of total phenol (5.79 mg/g), total flavonoid (8.95 mg/g), total anthocyanin (6.48 mg/g) and the greatest ability to inhibit DPPH free radical (42.56 %) and the lowest growth rate of mold and yeast (21 Cfu/g).

A Single Terminal [NiII-OH] Catalyst for Direct Julia-Type Olefination and α-Alkylation Involving Sulfones and Alcohols.

A terminal [NiII-OH] complex 1, supported by triflamide-functionalized NHC ligands, showed divergent reactivity for the reaction of sulfone with alcohol, contingent on base concentration, temperature, and time. Julia-type olefination of alcohols with sulfones was achieved using one equiv. of base, whereas lowering base loading to 0.5 equiv. afforded α-alkylated sulfones. Besides excellent substrate scope and selectivity, biologically active stilbene derivatives DMU-212, pinosylvin, resveratrol, and piceatannol were synthesized in high yield under Julia-type olefination conditions. An extensive array of controlled experiments and DFT calculations provide valuable insight on the reaction pathway.

Physico-Chemical Characterization, Phenolic Compound Extraction and Biological Activity of Grapevine (Vitis vinifera L.) Canes

Annual grapevine pruning produces large amounts of unused waste as woody canes. The current study is aimed at the sustainable valorization of viticultural waste by establishing phenolic compound extraction conditions, composition, and biological potential of crude and purified cane extracts of three Vitis vinifera L. cultivars growing in temperate climate conditions. Grapevine canes proved to be rich in carbohydrates and minerals; chlorophyll and carotenoids were also quantified. The highest yield of phenolic compounds was obtained when dry canes (<0.5 mm) were subjected to liquid–solid extraction (1:20 w/v) with 70% (v/v) ethanol, for 4 h at 35 °C, after a preliminary ultrasound treatment (6 min., 42 KHz); Pinot Gris canes showing the highest concentration of flavonoids and non-flavonoids. Stilbenes (resveratrol) and flavan-3-ols (catechin and epicatechin) were the main phenolic representative, resveratrol concentrations varying significantly between red-black (419.01–425.60 μg/g d.w.) and white (282.19 ± 4.14 μg/g d.w.) grape cultivars. Purified extracts (C-18 cartridge) exhibited higher antioxidant and antiradical activities compared to the crude extracts, and a higher antimicrobial effect, especially against Gram-positive (Staphylococcus aureus) pathogenic bacteria. Furthermore, Saccharomyces cerevisiae and Oenococcus oeni showed a reduced susceptibility even at high extract concentrations (>100 mg/mL). These findings indicate that grapevine canes represent a valuable source of natural bioactive compounds, that are currently insufficiently known and not exploited to their true functional and economic potential.

Phytoestrogens and Amenorrhea in Athletes

Plants contain several different families of natural products. Phytoestrogens are one such compound that is found in variety of plant foods. On the basis of the chemical structure, phytoestrogens are classified into four major categories such as flavonoids, isoflavonoids, lignans, and stilbenes. Structurally phytoestrogens are very much similar to 17 β-estradiol, so they have a tendency to exhibit estrogen-like activity, which has increased the interest of researchers to use it as a hormone replacement therapy. Nowadays, special attention is given to various isoflavonoids including genistein, diadzens, coumestrol, equol, and several prenylated flavonoids mainly, 8-prenylnaringein and stilbene resveratrol. Menstrual changes and bone density may be favorably influenced by phytoestrogens. These compounds have not only been observed to mimic the role of estrogen in humans but have also shown to exhibit effects and action in both similar and divergent manner as of the hormone. The eventual action of phytoestrogen in specific cells is determined by several factors such as the relative levels of estrogen receptors both α and β and the varied number and types of coactivators and corepressors presently existing in the cell. An increase in the consumption of herbal and natural nutritional supplements with ergogenic goals with particular regard to ecdysteroids, phytosterols, and vegetal sterols has been observed in past among the athletes which call for the need to assess the knowledge of athletes and physically active individuals about the plant-based nutritional supplements as well as its associations with amenorrhea in female athletes, their health profile, and reproductive life.

Abstract A072: Unique mouse models of high-risk prostate cancer adequate for targeted interception

Abstract Metastasis-associate protein 1 (MTA1), a master transcriptional co-regulator and chromatin modifier, is strongly associated with clinically aggressive prostate cancer. The loss of MTA1 reduces the aggressiveness and metastatic potential of prostate cancer cells. Preclinical studies with subcutaneous and orthotopic MTA1 knockdown xenograft models have shown the tumor promoting role of MTA1 and associated survival pathways in prostate cancer. However, the exact role of MTA1 in the pathobiology of prostate cancer is unknown. We first generated a conditional mouse with human MTA1 transgene knocked into the mouse Rosa26 locus (R26MTA1; Cre+ ). By crossing a R26MTA1 mouse with a Pten “floxed” mouse, we have created unique high-risk high-grade PIN-prone R26MTA1; Ptenf/+; Cre+ mice and a high-risk R26MTA1; Ptenf/f; Cre+ cohort of mice with characteristics of a castrate-resistant neuroendocrine subtype suitable for early chemoprevention/interception and novel effective therapies, respectively. I will discuss the potent MTA1-targeted anticancer effects of natural stilbenes (resveratrol, pterostilbene, and Gnetin C) observed in the preclinical R26MTA1; Ptenf/+; Cre+ model mimicking high-risk premalignant tumors with overexpressed MTA1. Further, evidence will be provided on the role of MTA1 in castrate resistance and on the neuroendocrine features defining the potential of the R26MTA1; Ptenf/f; Cre+ model in discovering novel chemoimmunotherapies. Our studies demonstrate progress towards successful targeted interception strategies for prostate cancer with an implication for precision medicine. Supported by the NCI/NIH R15CA216070 Award. Citation Format: Anait S. Levenson. Unique mouse models of high-risk prostate cancer adequate for targeted interception [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A072.

Determination of 21 polyphenols in fruits by high performance liquid chromatography

To establish a high performance liquid chromatography(HPLC) method for simultaneous determination of flavonoids(epicatechin, isoorientin, eriocitrin, hyperoside, narirutin, naringin, hesperidin, neohesperidin, quercetin, didymin, naringenin and hesperetin), phenolic acids(gallic acid, chlorogenic acid, caffeic acid, ferulic acid, sinapic acid and p-coumaric acid), terpenoids(limonin), stilbenes(piceatannol and resveratrol) in fruits. Add ethanol-water(4∶1, V/V) solution to the fruit pulp sample, ultrasonic extraction at 55 ℃ for 10 min, after centrifugation, the supernatant was dried and re-dissolved, and then eluted with ZORBAX Eclipse XDB-C_(18)(4.6 mm×100 mm, 3.5 μm) as chromatographic column, polyphenols are determined by HPLC under switching wavelength, and quantified by external standard method. The 21 polyphenols can be detected within 45 min and well separated from baseline, with linear correlation coefficients greater than 0.999, the detection limit of the method was 0.03-0.31 μg/g, and the limit of quantitation of the method was 0.09-1.03 μg/g. The intra-day precision was 0.5%-9.3%, the inter-day precision was 2.0%-9.6%. The recoveries of more than 90% polyphenols in the three fruits at three levels were between 80.0% and 119.8%. The relative standard deviation of spiked recoveries of three samples was less than 10.8%. The detection result of citrus, mango, blueberry, persimmon and other samples proved that the composition of polyphenols in different fruits was different. The method is sensitive, accurate and reproducible, and is suitable for the determination of polyphenols in fruits.

The Antibacterial Activity of Rhazya stricta Extracts against Klebsiella pneumoniae Isolated from Some Soil Invertebrates at High Altitudes.

Klebsiella is a common dangerous pathogen for humans and animals and is widely present in the digestive system. The genus Klebsiella is ubiquitous, as it is endemic to surface water, soil, and sewage. In this study, 70 samples were obtained from soil-dwelling invertebrates from September 2021 to March 2022 from Taif and Shafa in different altitudinal regions of Saudi Arabia. Fifteen of these samples were identified as Klebsiella spp. The Klebsiella isolates were genetically identified as Klebsiella pneumoniae using rDNA sequencing. The antimicrobial susceptibility of the Klebsiella isolates was determined. Amplification of virulence genes was performed using PCR. In this study, 16S rDNA sequencing showed a similarity from 98% to 100% with related K. pneumonia from the NCBI database, and the sequences were deposited in the NCBI GenBank under accession numbers ON077036 to ON077050. The growth inhibition properties of ethanolic and methanolic extracts of the medicinal plant Rhazya stricta's leaves against K. pneumoniae strains using the minimum inhibitory concentration (MIC) method and disc diffusion were evaluated. In addition, the biofilm inhibitory potential of these extracts was investigated using crystal violet. HPLC analysis identified 19 components divided into 6 flavonoids, 11 phenolic acids, stilbene (resveratrol), and quinol, and revealed variations in the number of components and their quantities between extracts. Both extracts demonstrated interesting antibacterial properties against K. pneumoniae isolates. The 2 extracts also showed strong biofilm inhibitory activities, with percentages of inhibition extending from 81.5% to 98.7% and from 35.1% to 85.8% for the ethanolic and methanolic extracts, respectively. Rhazya stricta leaf extract revealed powerful antibacterial and antibiofilm activities against K. pneumoniae isolates and could be a good candidate for the treatment or prevention of K. pneumonia-related infections.

Scavengome of an antioxidant.

The term "scavengome" refers to the chemical space of all the metabolites that may be formed from an antioxidant upon scavenging reactive oxygen or nitrogen species (ROS/RNS). This chemical space covers a wide variety of free radical metabolites with drug discovery potential. It is very rich in structures representing an increased chemical complexity as compared to the parent antioxidant: a wide range of unusual heterocyclic structures, new CC bonds, etc. may be formed. Further, in a biological environment, this increased chemical complexity is directly translated from the localized conditions of oxidative stress that determines the amounts and types of ROS/RNS present. Biomimetic oxidative chemistry provides an excellent tool to model chemical reactions between antioxidants and ROS/RNS. In this chapter, we provide an overview on the known metabolites obtained by biomimetic oxidation of a few selected natural antioxidants, i.e., a stilbene (resveratrol), a pair of hydroxycinnamates (caffeic acid and methyl caffeate), and a flavonol (quercetin), and discuss the drug discovery perspectives of the related chemical space.

Production of high molecular-ordered stilbene oligomers for the study of their biological activity: total synthesis, bio-catalyzed synthesis and production by plant systems.

Though the iconic stilbene resveratrol and its related dimers constitute a top storyline in the field of natural product research, resveratrol oligomers (condensation >2) have been left aside despite their higher biological activity compared to that of the monomers. This situation largely results from the difficulty of getting them in sufficient quantities to enable evaluation of their biological properties in vivo. We present here a synthetic and critical analysis of the methods used for the production of high molecular-ordered stilbene oligomers of potential biomedical interest, gathering the most salient data regarding the approaches employed to prepare them by total synthesis, use of biomimetic approaches or through plant systems.

Trans-gnetin H isolated from the seeds of Paeonia species induces autophagy via inhibiting mTORC1 signalling through AMPK activation.

Paeonia is a well-known species of ornamental plants, traditional Chinese medicines, and emerging oilseed crops. Apart from nutritional unsaturated fatty acids, the seeds of peonies are rich in stilbenes characterized by their wide-ranging health-promoting properties. Although the typical stilbene resveratrol has been widely reported for its multiple bioactivities, it remains uncertain whether the trimer of resveratrol trans-gnetin H has properties that regulate cancer cell viability, let alone the underlying mechanism. Autophagy regulated by trans-gnetin H was detected by western blotting, immunofluorescence, and quantitative real-time PCR. The effects of trans-gnetin H on apoptosis and proliferation were examined by flow cytometry, colony formation and Cell Counting Kit-8 assays. Trans-gnetin H significantly inhibits cancer cell viability through autophagy by suppressing the phosphorylation of TFEB and promoting its nuclear transport. Mechanistically, trans-gnetin H inhibits the activation and lysosome translocation of mTORC1 by inhibiting the activation of AMPK, indicating that AMPK is a checkpoint for mTORC1 inactivation induced by trans-gnetin H. Moreover, the binding of TSC2 to Rheb was markedly increased in response to trans-gnetin H stimulation. Similarly, trans-gnetin H inhibited the interaction between Raptor and RagC in an AMPK-dependent manner. More importantly, trans-gnetin H-mediated autophagy highly depends on the AMPK-mTORC1 axis. We propose a regulatory mechanism by which trans-gnetin H inhibits the activation of the mTORC1 pathway to control cell autophagy.

Abstract 5928: MTA1-targeted interception by natural stilbenes in high-risk prostate cancer

Abstract Active surveillance subpopulation of patients with prostate cancer includes men with varying cancer risk categories of precancerous disease due to prostatic intraepithelial neoplasia (PIN) heterogeneity. Identifying molecular alterations associated with PIN can provide preventable measures through finding novel targets for cancer interception, specifically by active dietary polyphenols with potent biological properties including anti-inflammatory, anti-oxidant, and anticancer effects. A large volume of preclinical evidence shows that natural stilbenes produce anticancer responses in a variety of cell lines and animal models of different types of cancer, including solid tumors as well as hematological malignancies. However, identification of a particular target with clinical relevance is rare. I will discuss the potent MTA1-targeted anticancer effects of natural stilbenes (resveratrol, pterostilbene, and Gnetin C) observed in unique preclinical models of prostate cancer mimicking high-risk premalignant tumors with overexpressed MTA1. We have shown that MTA1 cooperates with PTEN deficiency to accelerate high-grade PIN development through MTA1-associated signaling. We further demonstrated that stilbene supplemented diets lead to more favorable histopathology with decreased severity and number of PIN foci accompanied with reduced proliferation, inflammation, and angiogenesis concomitant to reduction of MTA1-associated signaling, including specific miRNAs. Together, our preclinical data provide strong evidence for the potential of stilbenes as promising natural agents for MTA1-targeted interceptive strategy. Human cancer prevention trials for protecting select patients with high MTA1 from developing into full-fledged disease are urgently needed. This can be one extra forward step towards viable and successful interception/chemoprevention potential for prostate cancer with an implication for precision medicine. Supported by NCI/NIH R15CA216070 to ASL. Citation Format: Anait S. Levenson. MTA1-targeted interception by natural stilbenes in high-risk prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5928.

Stilbenes (Resveratrol and Pterostilbene) Alter Intestinal Functionality, Morphology and the Microbiome in-vivo (Gallus gallus)

ObjectivesEvaluating the effect of Stilbenes (Resveratrol and pterostilbene) on brush border membrane (BBM) functionality, morphology, mineral status and the microbiome in-vivo (Gallus gallus). MethodsThe study employed the in-vivo intra-amniotic approach (Gallus gallus) to meet the objective. Six treatment groups viz. No Injection, 18 MΩ H2O, 5% Inulin, 5% Resveratrol, 5% Pterostilbene and Synergistic (4.75% resveratrol and 0.25% pterostilbene) were created with n∼10 for each group. Upon hatch, the blood, pectoral muscle, liver, cecum and duodenum samples were collected. Hemoglobin level, Fe and Zn content in the serum and liver, mRNA expression of liver and duodenum, duodenal morphological examination and the cecal microbiome were analyzed in the different groups. ResultsOur results demonstrated a significant increase in villus surface area, crypt depth and goblet cell diameter in the synergistic and pterostilbene group. These results were correlated to the increase in serum iron and zinc concentrations in these groups. In addition, the gene expression analysis revealed beneficial changes in mineral metabolism proteins and pro-inflammatory cytokines. Further, the 16S rRNA sequencing showed a lower α-diversity in the synergistic group compared to the others. Although, favorable bacterial compositional changes were observed. Several key metabolic pathways were found to be enriched in the group administered with pterostilbene. ConclusionsThe study provides promising evidence for the consumption of dietary stilbenes both resveratrol and pterostilbene. The 5% pterostilbene and synergistic groups improved BBM functionality and as a result led to an increase in mineral serum concentrations (Fe and Zn). This is the first study to demonstrate an effect of stilbenes on mineral absorption. Further studies are required to confirm our findings. Funding SourcesN/A.

Research of Dracocephalum palmatum S. and Dracocephalum ruyschiana L. originating from Yakutia and identification of metabolites by tandem mass spectrometry

Dracocephalum palmatum Stephan and Dracocephalum ruyschiana L. contains a large number of target analytes, which are biologically active compounds. High performance liquid chromatography (HPLC) in combination with a BRUKER DALTONIKS ion trap (tandem mass spectrometry) was used to identify target analytes in extracts of D. palmatum Stephan and D. ruyschiana L., originating from Yakutia. The results of initial studies revealed the presence of 61 compounds, of which 53 were identified for the first time in genus Dracocephalum. These are flavones: Apigenin 8-C-pentoside-6-C-hexoside, Apigenin 7-sulfate; Chrysin 6-C-glucoside, Chrysin glucuronide; flavanols: Kaempferol, Dihydrokaempferol, Astragalin; flavan-3-ol (epi)Catechin, phenolic acids: Methylgallic acid; Hydroxy methoxy dimethylbenzoic acid; Ellagic acid; Caffeoylshikimic acid; Prolithospermic acid; 3,4-O-dicaffeoylquinic acid; salvianolic acid G; stilbenes pinosylvin and resveratrol; anthocyanins Petunidin, Pelargonidin-3-O-glucoside; Peonidin-3-O-glucoside; Cyanidin 3-(acetyl)hexose; perillic acid; lignans: Hinokinin, Dimethyl-secoisolariciresinol, Podophyllotoxin, carotenoids: Apocarotenal, 5,8-epoxy-alpha-carotene; etc.

Antioxidant Activity and Mechanism of Resveratrol and Polydatin Isolated from Mulberry (Morus alba L.).

Natural stilbenes have unique physiological effects, such as anti-senile dementia, anti-cancer, anti-bacterial, lowering blood lipid, and other important biological functions, which have attracted great attention from scholars in recent years. In this study, two stilbene compounds, resveratrol (RES) and polydatin (PD), were isolated from Mulberry (Morus alba L.), and their antioxidant activity and mechanism were investigated. The results showed that the contents of RES and PD in mulberry roots were 32.45 and 3.15 μg/g, respectively, significantly higher than those in mulberry fruits (0.48 and 0.0020 μg/g) and mulberry branches (5.70 and 0.33 μg/g). Both RES and PD showed high antioxidant potential by DPPH, ABTS free-scavenging methods, and ORAC assay, and provided protection against oxidative damage in HepG2 cells by increased catalase (CAT) activity, superoxide dismutase (SOD) activity, and Glutathione (GSH) content, and decreasing generation of reactive oxygen species (ROS), lactate dehydrogenase (LDH) level, and malondialdehyde (MDA) content. Therefore, RES and PD treatment could be effective for attenuating AAPH-induced oxidative stress in HepG2 cells. This study will promote the development and application of stilbene compounds. Furthermore, the RES and PD could be used as antioxidant supplements in functional foods, cosmetics, or pharmaceuticals, contributing to health improvement.

Phytochemicals from Peanut (Arachis hypogaea L.) Skin Extract with Potential for Pharmacological Activity

Background: Plant phenolics, commonly present in legumes, leafy vegetables, fruits, grains are a key source of bioactive nutrients existing as flavonols, flavanones, flavanols, phytosterols, among others. Peanuts, being crops of high commercial use, undergo processing that generates voluminous agro-wastes. The waste comprises both the shells and skins, which could be valorized. Its versatile functionality has encouraged extensive research into peanut skin-derived chemicals for diverse applications over the past few decades. Peanut skin, however, is ascertained to be rich in flavonoids, stilbenes (resveratrol), and other phenolic compounds. Methods: This review presents the biologically active compounds and pharmacological activities of peanut skins and their related works over the past few years. Articles carefully chosen from broad databases such as Scopus, Science Direct, Pub Med, SciFinder, among others, were used as the primary data. Results: The bioactive components of peanut skin extracts exhibit anti-oxidant, anti-inflammatory, anti-bacterial, anti-viral, anti-fungal, anti-cancer/anti-tumour, anti-cardiovascular, and anti-diabetes/ obesity activities via in vitro and in vivo models. Besides, their varied biological properties make them potential precursors for the management of diverse diseases and ailments. Potential Applications: Phytochemicals from peanut skins could be deployed as antioxidant, antidiabetic and antimicrobial agents in drugs for the clinical treatment of ailments with extensive clinical applications. Conclusion: The present review covers the chemistry and pharmacological activities of peanut skin phytochemicals. Our findings in this review substantiate the importance of peanut skin extracts and their varied potential for the treatment of specific diseases. The results indicate that they are attractive target compounds for the development of new drugs. We hope that this information will inform further in vivo studies on the role of peanut skin phenolic compounds in our health.

Adlercreutzia rubneri sp. nov., a resveratrol-metabolizing bacterium isolated from human faeces and emended description of the genus Adlercreutzia.

The novel, anaerobic, Gram-positive, rod-shaped bacterial strain, ResAG-91T, was isolated from a faecal sample of a male human volunteer. Analysis of the 16S rRNA gene sequence revealed that strain ResAG-91T showed high similarity to the type strains of Adlercreutzia equolifaciens subsp. equolifaciens and Adlercreutzia equolifaciens subsp. celatus . Analysis of the whole draft genome sequences, i.e. digital DNA–DNA hybridization (dDDH) and average nucleotide identity (ANI), of strain ResAG-91T and the type strains of Adlercreutzia species revealed that strain ResAG-91T represents a novel species of the genus Adlercreutzia . The genome size of strain ResAG-91T is 2.8 Mbp and the G+C content is 63.3 mol%. The major respiratory quinone of strain ResAG-91T was MMK-5 (methylmenaquinone). Major cellular fatty acids were C15 : 0 anteiso, C14 : 0 iso and C14 : 0 2-OH. Galactose and ribose were detected as major whole cell sugars. Furthermore, the peptidoglycan type of strain ResAG-91T was A1γ with meso-diaminopimelic acid. The polar lipids were phosphatidylglycerol, diphosphatidylglycerol, one unidentified lipid, three unidentified phospholipids and five unidentified glycolipids. Strain ResAG-91T was able to metabolize the stilbene resveratrol into dihydroresveratrol. On the basis of this polyphasic approach, including phenotypical, molecular (16S rRNA gene and whole genome sequencing) and biochemical (fatty acids, quinones, polar lipids, peptidoglycan, whole cell sugars, Rapid ID32A and API20A) analyses, we propose the novel species Adlercreutzia rubneri sp. nov. with the type and only strain ResAG-91T (=DSM 111416T=JCM 34176T=LMG 31897T).

The Potential of Resveratrol to Act as a Caloric Restriction Mimetic Appears to Be Limited: Insights from Studies in Mice

Caloric restriction (CR) has been shown repeatedly to prolong the lifespan in laboratory animals, with its benefits dependent on molecular targets forming part of the nutrient signaling network, including the NAD-dependent deacetylase silent mating type information regulation 2 homologue 1 (SIRT1). It has been hypothesized that the stilbene resveratrol (RSV) may counteract age- and obesity-related diseases similarly to CR. In yeast and worms, RSV-promoted longevity also depended on SIRT1. While it remains unclear whether RSV can prolong lifespans in mammals, some studies in rodents supplemented with RSV have reported lowered body weight (BW) and fat mass, improved insulin sensitivity, lowered cholesterol levels, increased fitness, and mitochondrial biogenesis. Molecular mechanisms possibly leading to such changes include altered gene transcription and activation of SIRT1, AMP-activated kinase (AMPK), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A). However, some mouse models did not benefit from RSV treatment to the same extent as others. We conducted a literature search on PubMed (15 April, 2020) for trials directly comparing RSV application to CR feeding in mice. In most studies retrieved by this systematic PubMed search, mice supplemented with RSV did not show significant reductions of BW, glucose, or insulin. Moreover, in some of these studies, RSV and CR treatments affected molecular targets differently and/or findings on RSV and CR impacts varied between trials. We discuss those RSV-induced changes in gene transcription hypothesized to partly counteract age-related alterations. Although there may be a moderate effect of RSV supplementation on parameters such as insulin sensitivity toward a more CR-like profile in mice, data are inconsistent. Likewise, RSV supplementation trials in humans report controversial findings. While we consider that RSV may, under certain circumstances, moderately mimic some aspects of CR, current evidence does not fully support its use to prevent or treat age- or obesity-related diseases.

Bioassay-Guided Identification of the Antiproliferative Compounds of Cissus trifoliata and the Transcriptomic Effect of Resveratrol in Prostate Cancer Pc3 Cells

The bioassay-guided fractionation of a CHCl3-MeOH extract from the stems of Cissus trifoliata identified an active fraction against PC3 prostate cancer cells. The treatment for 24 h showed an 80% reduction in cell viability (p ≤ 0.05) by a WST-1 assay at a concentration of 100 μg/mL. The HPLC-QTOF-MS analysis of the fraction showed the presence of coumaric and isoferulic acids, apigenin, kaempferol, chrysoeriol, naringenin, ursolic and betulinic acids, hexadecadienoic and octadecadienoic fatty acids, and the stilbene resveratrol. The exposure of PC3 cells to resveratrol (IC25 = 23 μg/mL) for 24 h induced significant changes in 847 genes (Z-score ≥ ±2). The functional classification tool of the DAVID v6.8 platform indicates that the underlying molecular mechanisms against the proliferation of PC3 cells were associated (p ≤ 0.05) with the process of differentiation and metabolism. These findings provide experimental evidence suggesting the potential of C. trifoliata as a promising natural source of anticancer compounds.