Glycoside Rutin Research Articles

Interactions of gliadins with flavonoids and their glycosides studied with application of FT-Raman spectroscopy

FT-Raman spectroscopy was applied to study interactions between wheat gliadins and three flavonoids and their glycosides. Complexes gliadins-flavonoids/glycosides were extracted from the model wheat dough. As flavonoids were used quercetin, naringenin, hesperetin and their glycosides rutin, naringin, hesperidin in the amount of 0.05%, 0.1% and 0.2%. The analysis of the FT-Raman spectra showed that the tested compounds caused changes in the secondary and tertiary structure of gliadins. In the case of gliadins, these changes concerned mainly α-helices. Quercetin induced a different type of structural changes compared to naringenin and hesperetin, which was probably due to the presence of a double bond on the C ring and an additional OH group on the B ring in the structure of this molecule. On the other hand, the interactions of glycosides with gliadins were affected by the place of attachment of the sugar part in the structure of the glycoside. Flavonoids/glycosides significantly increased the content of disulfide bridges in the g-g-g conformation. Changes in the amino acid microenvironment (tyrosine and tryptophan) indicate the formation of a more ordered structure in gliadins.

Elder (Sambucus nigra), identified by high-content screening, counteracts foam cell formation without promoting hepatic lipogenesis

Cholesterol deposition in intimal macrophages leads to foam cell formation and atherosclerosis. Reverse cholesterol transport (RCT), initiated by efflux of excess cholesterol from foam cells, counteracts atherosclerosis. However, targeting RCT by enhancing cholesterol efflux was so far accompanied by adverse hepatic lipogenesis. Here, we aimed to identify novel natural enhancers of macrophage cholesterol efflux suitable for the prevention of atherosclerosis. Plant extracts of an open-access library were screened for their capacity to increase cholesterol efflux in RAW264.7 macrophages trace-labeled with fluorescent BODIPY-cholesterol. Incremental functional validation of hits yielded two final extracts, elder (Sambucus nigra) and bitter orange (Citrus aurantium L.) that induced ATP binding cassette transporter A1 (ABCA1) expression and reduced cholesteryl ester accumulation in aggregated LDL-induced foam cells. Aqueous elder extracts were subsequently prepared in-house and both, flower and leaf extracts increased ABCA1 mRNA and protein expression in human THP-1 macrophages, while lipogenic gene expression in hepatocyte-derived cells was not induced. Chlorogenic acid isomers and the quercetin glycoside rutin were identified as the main polyphenols in elder extracts with putative biological action. In summary, elder flower and leaf extracts increase macrophage ABCA1 expression and reduce foam cell formation without adversely affecting hepatic lipogenesis.

Preparation of isoquercitrin and rhamnose from readily accessible rutin by a highly specific recombinant α-L-rhamnosidase (r-Rha1)

Isoquercitrin has superior in vivo bioactivities with respect to its primary glycoside rutin. Its conventional preparation was ineffective, with large chemical consumption and many by-products. Rhamnose, a high value-added monosaccharide, is usually separated from acid hydrolytes of rutin. This study aimed to establish a novel enzymatic hydrolysis-based approach for their preparation. α-L-rhamnosidase was expressed in Pichia pastoris GS115 and applied to enzymolysis of rutin. Then, one-factor-at-a-time optimisation of hydrolysis conditions was performed. Two compounds were produced in 0.02 M HAc-NaAc buffer (pH4.50) containing α-L-rhamnosidase/rutin (1:4, w/w) at 60 °C. Consequently, 20.0 g/L rutin was completely hydrolysed in 2 hrs, and isoquercitrin was obtained after purification by HPD-100 resin. Additionally, rhamnose was enriched by decolorisation and crystallisation. MD simulation analysis suggested that rutin was catalysed on the hydrophobic surface of r-Rha1 with van-der-Waals force being main driving force. This strategy is an efficient approach for preparation of isoquercitrin and rhamnose.

Lipase inhibitory activity of constituents of Physalis glutinosa and Physalis latiphysa

The new labdane-type diterpenoid, physaglutinic acid (1), was isolated from the hexane extract of Physalis glutinosa. This compound is the first succinyl labdane isolated from a Physalis species. The known constituents of this plant were identified as the labdanes 12-O-acetylphysacoztomatin (3), physacoztomatin (4) and 12-epi-nicandrodiol (6). The flavonol retusin (8) was also isolated from this species. The investigation of the acetone extract of Physalis latiphysa resulted in the isolation of the known (+)- (Z)-labda-8(17),13-diene-15,16-diol (9), labdenediol (11), the epimeric mixture of physanicantriol (12) and 14 epi-physanicantriol (13), together with the sucrose esters, nicandroses B (15) and D (16). Also, a large amount of the flavonol glycoside rutin (17) was obtained from the methanol extract. The activity of eight of the isolated compounds and three of their derivatives as lipase inhibitors was determined. The mode of binding of active compounds 4, 10 and 16 was explored using molecular docking on the binding pocket of pancreatic lipase (PDB ID 1LPB).

Biotransformation of Rutin in In Vitro Porcine Ileal and Colonic Fermentation Models.

Quercetin, a polyphenol antioxidant, is widely distributed in food in the form of glycoside rutin, which is not readily absorbed in the gastrointestinal tract. The microbiota of the colon is known to biotransform rutin, generating quercetin aglycones that can be absorbed. We investigated the role of the ileal and colonic microbiota in rutin biotransformation using established in vitro fermentation models. Overall, a higher rate of rutin biotransformation was observed during colonic fermentation compared with ileal fermentation. The colonic microbiome showed higher potential for rutin conversion to quercetin through an increased abundance of α-rhamnosidase- and β-glucosidase-encoding genes compared to the ileal microbiome. Nonetheless, rutin metabolism occurred rapidly during ileal fermentation (∼20% rutin disappearance after 1 h). The appearance of quercetin varied depending on the ileal inoculum and correlated with an increased abundance of Firmicutes, suggesting that quercetin absorption could be improved via modulation of the ileal microbiota.

Hydrolyzed Flavonoids from Cyrtosperma johnstonii with Superior Antioxidant, Antiproliferative, and Anti-Inflammatory Potential for Cancer Prevention.

Cyrtosperma johnstonii is one of the most interesting traditional medicines for cancer treatment. This study aimed to compare and combine the biological activities related to cancer prevention of the flavonoid glycosides rutin (RT) and isorhamnetin-3-o-rutinoside (IRR) and their hydrolysis products quercetin (QT) and isorhamnetin (IR) from C. johnstonii extract. ABTS and MTT assays were used to determine antioxidant activity and cytotoxicity against various cancer cells, as well as normal cells. Anti-inflammatory activities were measured by ELISA. The results showed that the antioxidant activities of the compounds decreased in the order of QT > IR > RT > IRR, while most leukemia cell lines were sensitive to QT and IR with low toxicity towards PBMCs. The reduction of IL-6 and IL-10 secretion by QT and IR was higher than that induced by RT and IRR. The combination of hydrolysis products (QT and IR) possessed a strong synergism in antioxidant, antiproliferative and anti-inflammatory effects, whereas the combination of flavonoid glycosides and their hydrolysis products revealed antagonism. These results suggest that the potential of the combination of hydrolyzed flavonoids from C. johnstonii can be considered as natural compounds for the prevention of cancer.

Ursane-type triterpenoids, steroids and phenolics from the stem bark and leaves of Nauclea orientalis (L.) L. (Rubiaceae)

Phytochemical investigation of the stem bark and leaf extract of Nauclea orientalis led to the isolation and identification of the three ursane-type triterpenoids rotundic acid, (3β)-3,19,23,24-tetrahydroxyurs-12-en-28-oic acid, 3-oxo-19,23,24-trihydroxyurs-12-en-28-oic acid, the two steroids β-sitosterol, β-sitostenone, the two megastigmane derivatives blumenol A and blumenol A glucoside, the isocoumarine trans-4-hydroxymellein, as well as the flavonole glycoside rutin. From the crude stem bark extract, we performed an anti-bacterial assay against four Gram positive and six Gram negative bacterial strains. An acetylcholinesterase inhibitory assay was performed from the crude extracts and rotundic acid, (3ß)-3,19,23,24-tetrahydroxyurs-12-en-28-oic acid and β-sitostenone. Both assays showed only weak effects. Contact toxicity determined via topical application revealed increased mortality of Spodoptera exigua caterpillars. The chemophenetic significance of ursane-type triterpenoids for the genus Nauclea is discussed briefly.

STUDY OF ORGANIC ACIDS PROFILE OF GENUS PERSICARIA MILL SPECIES

The genus Persicaria Mill. species belonging to the buckwheat family (Polygonaceae Juss.) and widespread in Russia, are weeds. The chemical composition’s main components of the genus Persicaria Mill. species, are flavonoid glycosides (rutin, avicularin, hyperoside, etc.). The data concerning a comparative study of the organic acids in the herb representatives of genus Persicaria Mill., have not been detected in the available literature.The aim of the research is a comparative study of the organic acids qualitative and quantitative composition in the genus Persicaria Mill. species growing in the Voronezh region.Materials and methods. The objects of the study were dried herb samples of the genus Persicaria Mill. species. All the species were harvested in the Voronezh region during the blooming period. The quantitative content of ascorbic acid and the amount of organic acids in terms of malic (hydroxy-succinic) acid was carried out according to the titrimetric methods of the Russian Federation State Pharmacopeia, the XIVth ed. The study of the qualitative composition of the organic acids profile and their quantitative content assessment in the studied objects, the herbs, was carried out by the method of capillary electrophoresis (“Kapel”, St. Petersburg, Russia).Results. With the help of pharmacopoeial titrimetric methods, it was established that the highest content of the organic acids total amount is characteristic of the Persicaria maculosa Mill. herb (5,60%), the lowest one – of the Persicaria tomentósa (Schrank) E. P. Bicknell herb (4.03%). Persicaria maculosa S. F. Gray and Persicaria hydropiper (L.) Delarbre are the richest in ascorbic acid (0.17% and 0.15%, respectively). Using the method of capillary electrophoresis, the composition of the total amount of the studied organic acids has been established. It is represented by oxalic, formic, citric, malic, wine, propionic, lactic, benzoic and other acids.Conclusion. The study of the organic acids of the genus Persicaria Mill. species has been carried out. It has been established that in the studied species, the organic acids total amount in terms of malic acid and the amount of ascorbic acid are similar. By the method of capillary electrophoresis, a complete composition of organic acids has been studied, and the quantitative content of each component has been established. In all the studied Persicaria Mill. species, the predominance of oxalic, formic and malic acids has been revealed.

New molecular complex of ammonium glycyrrhizate with rutin

A new 1:1 molecular complex of triterpene glycoside ammonium glycyrrhizate (GC) with flavonoid glycoside rutin (Rut) was obtained in aqueous ethanol. The stability constant (9.7±0.2)×104 (mol/L)–1 was calculated for the complex via isomolar curves. The complexation was studied by UV- and ATR IR-Fourier spectroscopy and a method of isomolar series. The hydrogen bonds and hydrophobic interactions are formed in the molecular complex. A preliminary antioxidant activity assessment of the complex was made.

Identification of Flavonoids in the Leaves of Eranthis longistipitata (Ranunculaceae) by Liquid Chromatography with High-Resolution Mass Spectrometry (LC-HRMS)

Eranthis longistipitata Regel is an endemic plant of Central Asia. The flavonoid profile of E. longistipitata leaves was studied by mass spectrometry for the first time (natural populations of Kyrgyzstan and Uzbekistan, in 70% aqueous–ethanol extracts by liquid chromatography coupled with high-resolution mass spectrometry). Mass spectrometry revealed 18 flavonoid compounds. Flavonols featured the highest diversity, and 10 such substances were identified: 2 free aglycones (quercetin and kaempferol), 6 quercetin glycosides (peltatoside, hyperoside, reynoutrin, quercetin 3-sambubioside, rutin, and isoquercitrin), and 2 kaempferol glycosides (juglalin and trifolin). Two flavans (cianidanol and auriculoside), two hydroxyflavanones (6-methoxytaxifolin and aromadendrin), and one C-glycoside flavone—carlinoside—were identified. Dihydroxychalcones aspalathin, phloridzin, and phloretin were found too. Levels of rutin, quercetin, kaempferol, and hyperoside were confirmed by means of standards and high-performance liquid chromatography. Rutin concentration was the highest among all other identified flavonoid compounds: in the leaf samples from Kyrgyzstan, it ranged from 2.46 to 3.20 mg/g, and in those from Uzbekistan, from 1.50 to 3.01 mg/g. The diversity of flavonoid compounds in E. longistipitata leaves is probably due to external ecological and geographic factors and adaptive mechanisms.

L-Arginine Improves Solubility and ANTI SARS-CoV-2 Mpro Activity of Rutin but Not the Antiviral Activity in Cells.

The COVID-19 pandemic outbreak prompts an urgent need for efficient therapeutics, and repurposing of known drugs has been extensively used in an attempt to get to anti-SARS-CoV-2 agents in the shortest possible time. The glycoside rutin shows manifold pharmacological activities and, despite its use being limited by its poor solubility in water, it is the active principle of many pharmaceutical preparations. We herein report our in silico and experimental investigations of rutin as a SARS-CoV-2 Mpro inhibitor and of its water solubility improvement obtained by mixing it with l-arginine. Tests of the rutin/l-arginine mixture in a cellular model of SARS-CoV-2 infection highlighted that the mixture still suffers from unfavorable pharmacokinetic properties, but nonetheless, the results of this study suggest that rutin might be a good starting point for hit optimization.

Interactions between polyphenolic antioxidants quercetin and naringenin dictate the distinctive redox-related chemical and biological behaviour of their mixtures

Food synergy concept is suggested to explain observations that isolated antioxidants are less bioactive than real foods containing them. However, mechanisms behind this discrepancy were hardly studied. Here, we demonstrate the profound impact of interactions between two common food flavonoids (individual: aglycones quercetin—Q and naringenin—N− or their glycosides rutin—R and naringin—N+ vs. mixed: QN− and RN+) on their electrochemical properties and redox-related bioactivities. N− and N+ seemed weak antioxidants individually, yet in both chemical and cellular tests (DPPH and CAA, respectively), they increased reducing activity of mixtures synergistically. In-depth measurements (differential pulse voltammetry) pointed to kinetics of oxidation reaction as decisive factor for antioxidant power. In cellular (HT29 cells) tests, the mixtures exhibited properties of a new substance rather than those of components. Pure flavonoids did not influence proliferation; mixtures stimulated cell growth. Individual flavonoids tended to decrease global DNA methylation with growing concentration; this effect was more pronounced for mixtures, but not concentration-dependent. In nutrigenomic studies, expression of gene set affected by QN− differed entirely from common genes modulated by individual components. These results question the current approach of predicting bioactivity of mixtures based on research with isolated antioxidants.

Phytochemical analysis, antipropulsive and antilymphoma activities of leaves extract of Annona cherimola miller

Background: Diarrhea and cancer are significant health problems worldwide. Annona cherimola Mill. (Annonaceae) is a fruit tree extensively used in Mexican traditional medicine for the treatment of diarrhea and cancer. Objectives: The present work reports the identification of flavonol glycosides present in the ethanol crude extract using high-performance liquid chromatography with diode array detection (HPLC-DAD). Materials and Methods: The identification of flavonoids was made by comparing their retention times and ultraviolet spectra with those standards. The crude extract, dichloromethane, and aqueous residual (AR) fractions were tested for their antipropulsive and antilymphoma activities. Results: The results revealed high levels of three flavonoid glycosides (rutin, nicotiflorin, and narcissin), especially rutin (24.5 mg/g of extract). The antipropulsive and antilymphoma activities of the leaf extract and subsequent fractions showed that the ethanol extract of the leaves of A. cherimola is cursive and AR fraction exhibited the best biological effects in both assays. Conclusion: The HPLC-DAD method used in this work enables the determination of rutin as a major flavonol glycoside of the leaves of A. cherimola . In addition, it can be suggested that rutin may play an important role in the biological properties of A. cherimola.

Structure-Activity Relationships Analysis of Monomeric and Polymeric Polyphenols (Quercetin, Rutin and Catechin) Obtained by Various Polymerization Methods.

Plant polyphenols, especially flavonoids, are active and pro-health substances found in fruits and vegetables. Quercetin and its glycoside rutin are representatives of flavonoids, commonly found in plant products. Catechins found in large quantities in tea are also a well-known group of natural polyphenols. These compounds are based on the structure of flavan-3-ol, which is why the number, positions and types of substitutions affect the scavenging of radicals and other properties. Despite some inconsistent evidence, several structure-activity relationships of monomeric flavonoids are well established in vitro. However, the relationships between the activity and other properties of the polymeric forms of flavonoids and their structures are poorly understood so far. The aim of this article is to compare the data on polymerization of quercetin, rutin and catechin, as well as to systematize knowledge about the structure-activity relationship of the polymeric forms of these compounds.

Chromatographic study of the component composition and antioxidant activity of polyphenol complex in biological raw materials

Recently, the attention of many researchers has been attracted by raw materials that contain flavonoids. The purpose of the research is to summarize the results of studies of the composition of flavonoids of a non-fat sea buckthorn meal, which is a secondary raw material for the production of sea buckthorn oil. In this case, the sum of the five identified flavonoid compounds was isolated by extraction and subsequent adsorption column chromatography. At this stage, the actual problem of identifying and determining individual isolated flavonoids was solved using chromatographic (TLC, HPLC) and spectroscopic methods in comparison with reliably known samples. During the study, the flavonoids were identified: isorhamnetin, kaempferol, myritin, quercetin and its glycoside rutin, quercetin and isorhamnetin predominate. Ultimately, the effective parameters of the method for the improvement of the competitiveness of dietary supplements are established.

Target Discovery of Novel α-L-Rhamnosidases from Human Fecal Metagenome and Application for Biotransformation of Natural Flavonoid Glycosides.

As a green and powerful tool, biocatalysis has emerged as a perfect alternative to traditional chemistry. The bottleneck during process development is discovery of novel enzymes with desired properties and independent intellectual property. Herein, we have successfully bioprospected three novel bacterial α-L-rhamnosidases from human fecal metagenome using a combinatorial strategy by high-throughput de novo sequencing combined with in silico searching for catalytic key motifs. All three novel α-L-rhamnosidases shared low sequence identities with reported (< 35%) and putative ones (< 57%) from public database. All three novel α-L-rhamnosidases were over-expressed as soluble form in Escherichia coli with high-level production. Furthermore, all three novel α-L-rhamnosidases hydrolyzed the synthetic substrate p-nitrophenyl α-L-rhamnopyranoside and natural flavonoid glycosides rutin and naringin with some excellent properties, such as high activity in acidic pH, high activity at low or high temperature, and good tolerance for alcohols and DMSO. Our findings would provide a convenient route for target discovery of the promising biocatalysts from the metagenomes for biotransformation and biosynthesis.

Rutin attenuates vancomycin-induced renal tubular cell apoptosis via suppression of apoptosis, mitochondrial dysfunction, and oxidative stress.

Vancomycin is a glycopeptide antibiotic widely used to treat infections caused by methicillin-resistant Staphylococcus aureus. However, nephrotoxicity is a major adverse side effect, and the development of effective nephroprotective agents remains a priority in antimicrobial chemotherapy. In this study, we investigated the cell protective effects of the flavonol glycoside rutin against vancomycin-induced toxicity. Vancomycin added to porcine renal tubular LLC-PK1 cells caused an increase of production of intracellular reactive oxygen species and subsequent apoptotic cell death. Pretreatment of LLC-PK1 cells with rutin at 5, 10, and 20μM for 2hr prior to 2-mM vancomycin exposure for 24hr significantly decreased intracellular reactive oxygen species and increased superoxide dismutase and catalase activities. Rutin pretreatment also protected cells from vancomycin-induced caspase activation, mitochondrial membrane depolarization, and subsequent apoptosis. This study demonstrates a protective effect of rutin and suggests that rutin coadministration is an alternative therapy for treatment of vancomycin-induced nephrotoxicity.

Natural Therapies of the Inflammatory Bowel Disease: The Case of Rutin and its Aglycone, Quercetin.

Inflammatory bowel disease (IBD), commonly represented by ulcerative colitis and Crohn's disease, is a form of chronic inflammatory disorders of the gastrointestinal system. Its current drug treatment includes the use of antibiotics, 5-aminosalicylates, corticosteroids, immune-modifying agents and biologics such as anti-TNF agents and adhesion molecules blockers. These drugs have inherent problems of efficacy as many IBD sufferers need surgical intervention at some stage, high cost especially for the protein-based drugs, loss of efficacy and unwanted side effects. The discovery of novel drugs including those from natural sources that overcome the above mentioned drawbacks of the current therapy is therefore of great interest. While the flavonoid quercetin with proven antiinflammatory effect failed to show activity in vivo, its glycoside rutin has recently proven to possess a significant IBD therapeutic potential in experimental animals. In this communication, the pharmacological and pharmacokinetic profiles of rutin along with its ability to serve as a prodrug that deliver the bioactive quercetin close to the IBD site are discussed. Potential mechanisms of action far beyond antioxidant effects such as suppression of proinflammatory mediators' release and expression of inflammatory proteins (e.g. adhesion molecules, cyclooxygenase, nitric oxide synthase, etc.) are also scrutinized.

Rutin as A Novel c-Met Inhibitory Lead for The Control of Triple Negative Breast Malignancies

ABSTRACTTriple negative breast cancer (TNBC) has high metastatic and mortality potential and lacks effective and selective therapeutic options. Aberrant dysregulation of the receptor tyrosine kinase c-Met promotes TNBC progression, motility and survival and therefore considered a valid therapeutic target. Among various identified anticancer agents, plant polyphenols (PPs) including flavonoids, have been shown to be safe and proven for their antitumor activity through modulating diverse macromolecular targets. This study reports the bioassay-guided identification of the common flavonol glycoside rutin as breast cancer cell proliferation, migration and invasion inhibitor. The cell free Z′-LYTE kinase assay, Western blot and in silico docking experiments uncovered, for the first time, c-Met kinase as a potential mechanistic target for rutin-mediated anticancer effects on TNBC cell lines. Likewise, the intraperitoneal injection of rutin at 30 mg/kg, 3X/week, significantly reduced the growth of the TNBC MDA-MB-231/GFP orthotopic xenograft in nude mouse model. These results clearly designate the functional dietary flavonoid rutin as a potential lead for the prevention and control of c-Met-dependent breast malignancies.

Biochemical composition of promising leaves genotypes of buckwheat grown in Himachal Pradesh

Buckwheat originated from China and being cultivated all over the world, and has become a prominent pseudocereal. Among the pseudocereals (amaranthus, buckwheat and quinoa), buckwheat plant is economically important primarily due to their carbohydrate and protein rich grains, short growth span; besides foliage being used as a green vegetable and commercial source of the glycoside rutin used in medicine. In the present study, an attempt was made to evaluate the biochemical constituents of nutritional and nutraceutical significance of fourteen promising leaves genotypes of common buckwheat grown in Sangla region by following standard procedures. Wide variations in moisture content, crude protein, fat, ash, crude fiber, carbohydrates, ascorbic acid, oxalate and in vitro protein digestibility were observed to range from 87.4 to 92.2 %, 22.4 to 30.4 %, 1.8 to 3.7 %, 10.6 to 15.4 %, 12.0 to 13.9 %, 34.8 to 42.4 %, 25.0 to 29.2 mg/100g, 1375 to 1390 mg/100g and 53.4 to 65.1 % in that order. The content of minerals such as potassium, phosphorus, calcium, magnesium, zinc, manganese and copper varied from 1767.5 to 2035.0 mg/100g, 808 to 910 mg/100g, 394 to 409 mg/100g, 232.0 to 248.2 mg/100g, 3.1 to 6.1 mg/100g, 20.4 to 29.8 mg/100g and 0.2 to 1.4 mg/100g respectively. Based on cumulative grading done in respect of nutritionally desirable quality i.e., protein, ash, crude fiber, carbohydrates, ascorbic acid, in vitro protein digestibility, calcium, phosphorus, iron and oxalate content, the genotype IC-323731 followed by Kullugangetri and VL-27 emerged out to be overall superior versatile cultivars for cultivation under dry temperate climate.