Flavonol Glycoside Rutin Research Articles

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).

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.

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.

An effective identification and quantification method for Ginkgo biloba flavonol glycosides with targeted evaluation of adulterated products

BackgroundGinkgo biloba L. (Ginkgoaceae) leaf extract is one of the most popular herbal products on the market, as it contains flavone glycosides (≥ 24%) and terpene lactones (≥ 6%), which are proposed to have significant physiological effects. Unfortunately, the challenging financial climate has resulted in a natural health product market containing adulterated ginkgo products. Purpose42 ginkgo samples were analyzed to establish an HPLC profile for authentic ginkgo and common ginkgo adulterants, and to develop a method capable of easily detecting adulteration in ginkgo commercial products. MethodIn this study an efficient and targeted HPLC analysis method was established that is capable of distinguishing flavonol glycosides and aglycones simultaneously for the evaluation of ginkgo powdered extracts (PEs) and finished products in a single, 13min run. Thirteen ginkgo leaf samples, fifteen standardized powdered extracts, and fourteen commercially available ginkgo products have been analyzed using this new HPLC method. Chromatograms were compared to six standard reference materials: one flavonol glycoside (rutin), three aglycones (quercetin, kaempferol and isorhamnetin), and two isoflavones (genestin and genistein). The quantitative chromatographic data was interpreted by principal component analysis (PCA), which assisted in the detection of unexpected chromatographic features in various adulterated botanical products. ResultsOnly three of the commercially available ginkgo finished products tested in this study were determined to be authentic, with flavonol glycoside rutin, and aglycones quercetin, kaempferol, and isorhamnetin found to be common adulterants in the ginkgo powdered extract and finished product samples. ConclusionDespite evidence of adulteration in most of the samples, each of the samples discussed herein met most of the current pharmacopeial standards. It is therefore critical that a preliminary evaluation be utilized to detect adulteration in commercial ginkgo products, prior to the acid hydrolysis procedure utilized in the current testing methods.

Varietal Differences in the Flavonol Content of Mulberry (Morus spp.) Leaves and Genetic Analysis of Quercetin 3-(6-Malonylglucoside) for Component Breeding

The varietal differences in the flavonol glycosides rutin, isoquercitrin, kaempferol 3-(6-rhamnosylglucoside), quercetin 3-(6-malonylglucoside), astragalin, quercetin 3-(6-acetylglucoside), and kaempferol 3-(6-malonylglucoside) contained in mulberry leaves were elucidated. This information was used for breeding mulberry cultivars with a high concentration of functional components. The flavonol content, composition, and proportion in leaves varied widely. 'Kobuchizawa 1' had the highest level of total flavonols (1819 mg/100 g of dry weight), 5 times higher than that of 'Mikurasima 15' (393 mg/100 g of dry weight). Quercetin 3-(6-malonylglucoside) was the most abundant flavonol, although it was not found in all cultivars. Quercetin 3-(6-acetylglucoside) was only found in 'Keguwa'. From the quercetin 3-(6-malonylglucoside) content in crossbred offspring, malonyltransferase, an enzyme involved in quercetin 3-(6-malonylglucoside) synthesis, was acquired according to Mendelian inheritance. An offspring with a higher quercetin 3-(6-malonylglucoside) level than both parents was obtained from the crossing. This suggested that crossbreeding was effective for acquiring cultivars with a higher content of quercetin 3-(6-malonylglucoside).

Hepatoprotective and Free Radical Scavenging Activities of Extracts and a Major Compound Isolated from the Leaves of Cineraria abyssinica Sch. Bip. exA. Rich.

In Ethiopian traditional medicine the aqueous decoction of the leaves of Cineraria abyssinica Sch. Bip. exA. Rich (Asteraceae) is used for the treatment of various ailments including liver diseases, however, to date, there appears to have been no scientific report on the phytochemistry and claimed hepatoprotective activity of the plant. The main purpose of this study was, therefore, to carry out hepatoprotective and antioxidant activities of the leaf extracts of C. abyssinica. Hepatoprotective activities of the aqueous and 80% methanolic extracts as well as the methanol fraction of the leaves of C. abyssinica were investigated against carbon tetrachloride-induced liver damage in rats. Intraperitoneal administration of 2 ml/kg of CCl4 (50% in liquid paraffin) significantly (p < 0.001) raised the plasma levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT ) and aspartate aminotransferase (AST) in the toxin group compared with the values in the control group. Pretreatment of rats with 200 mg/kg of the aqueous, 80% methanol extracts and the methanol fraction reduced the toxin-induced rise in plasma ALP (65%, 75.4%, 85%), ALT (46.1%, 42.3%, 75%), and AST (58%, 98%, 79%), respectively. The standard drug, silymarin (100 mg/kg) reduced serum ALP (88%), ALT (92%), and AST (87.3%). Bioactivity-guided fractionation of the methanol fraction resulted in the isolation of the flavonol glycoside rutin, whose structure was assigned on the basis of spectroscopic methods. The results of biochemical analysis were further verified by histopatholgical examination of the liver, which showed improved architecture, absence of necrosis and a decrease in inflammation, compared with the findings in the toxin group of animals. Both the extracts and rutin showed potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activities. Acute toxicity studies showed that the total extracts of the plant are nontoxic up to a dose of 3 g/kg. The present study revealed for the first time the presence of a hepatoprotective and antioxidant phytochemical in the leaves of C. abyssinica that scientifically validates the traditional use of the plant and its potential for the treatment of liver disorders.

Biocontrol Treatments Confer Protection Against Verticillium dahliae Infection of Potato by Inducing Antimicrobial Metabolites

Verticillium wilt, caused by Verticillium dahliae Kleb., is a serious potato (Solanum tuberosum L.) disease worldwide, and biocontrol represents a promising eco-friendly strategy to reduce its impact. We used extracts from Canada milk vetch (CMV) and a set of four V. dahliae-antagonistic bacterial strains to coat potato seeds at planting and examined the degree of protection provided against V. dahliae as well as accumulation of soluble phenolics as markers for induced resistance. All tested treatments were effective in reducing disease severity, and CMV showed the highest level of protection. In this treatment, flavonol-glycoside rutin was a highly abundant compound induced in potato tissues, with levels two to three times higher than those detected in noninoculated controls and V. dahliae-inoculated plants. We investigated dose-dependent effects of rutin on V. dahliae growth and sporulation in vitro and in planta. The effect of rutin on mycelial growth was inconsistent between disk assay and amended medium experiments. On the other hand, significant reduction of V. dahliae sporulation in vitro was consistently observed starting at 300 and 100 μM for isolates Vd-9 and Vd-21, respectively. We successfully detected 2-protocatechuoylphloroglucinolcarboxylic acid (2-PCPGCA) using ultra-performance liquid chromatography tandem mass spectrometry, indicating that V. dahliae dioxygenally oxidizes quercetin. Quercetin, as an aglycone, is freed from the sugar moiety by glucosidases and rhamnosidases produced by the fungus and is a substrate for quercetinases. The occurrence of quercetinases in V. dahliae provides a background to formulate a hypothesis about how by-product 2-PCPGCA may be interfering with potato defenses.

Content of phenolic compounds and antioxidant capacity in fruits of apricot genotypes.

Research on natural compounds is increasingly focused on their effects on human health. In this study, we were interested in the evaluation of nutritional value expressed as content of total phenolic compounds and antioxidant capacity of new apricot (Prunus armeniaca L.) genotypes resistant against Plum pox virus (PPV) cultivated on Department of Fruit Growing of Mendel University in Brno. Fruits of twenty one apricot genotypes were collected at the onset of consumption ripeness. Antioxidant capacities of the genotypes were determined spectrometrically using DPPH• (1,1-diphenyl-2-picryl-hydrazyl free radicals) scavenging test, TEAC (Trolox Equivalent Antioxidant Capacity), and FRAP (Ferric Reducing Antioxidant Power)methods. The highest antioxidant capacities were determined in the genotypes LE-3228 and LE-2527, the lowest ones in the LE-985 and LE-994 genotypes. Moreover, close correlation (r = 0.964) was determined between the TEAC and DPPH assays. Based on the antioxidant capacity and total polyphenols content, a clump analysis dendrogram of the monitored apricot genotypes was constructed. In addition, we optimized high performance liquid chromatography coupled with tandem electrochemical and spectrometric detection and determined phenolic profile consisting of the following fifteen phenolic compounds: gallic acid, 4-aminobenzoic acid, chlorogenic acid, ferulic acid, caffeic acid, procatechin, salicylic acid, p-coumaric acid, the flavonols quercetin and quercitrin, the flavonol glycoside rutin, resveratrol, vanillin, and the isomers epicatechin, (–)- and (+)- catechin.

In vitro anti-HIV and -HSV activity and safety of sodium rutin sulfate as a microbicide candidate

Sodium rutin sulfate (SRS) is a sulfated rutin modified from the natural flavonol glycoside rutin. Here, we investigated its in vitro anti-HIV and -HSV activities and its cytotoxic profile. Fifty percent inhibitory concentration (IC 50) values of SRS against HIV-1 X4 virus IIIB, HIV-1 R5 isolates Ada-M and Ba-L were 2.3 ± 0.2, 4.5 ± 2.0 and 8.5 ± 3.8 μM with a selectivity index (SI) of 563, 575 and 329, respectively. Its IC 50 against primary R5 HIV-1 isolate from Yunnan province in China was 13.1 ± 5.5 μM, with a SI of 197. In contrast, unsulfated rutin had no activity against any of the HIV-1 isolates tested. Further study indicated that SRS blocked viral entry and virus–cell fusion likely through interacting with the HIV-1 envelope glycoprotein. SRS also demonstrated some activity against human herpes simplex virus (HSV) with an IC 50 of 88.3 ± 0.1 μM and a SI of 30. The 50% cytotoxicity concentration (CC 50) of SRS was >3.0 mM, as determined in human genital ME180, HeLa and primary human foreskin fibroblast cells. Minimum inhibitory concentration of SRS for vaginal lactobacilli was >3.0 mM. These results collectively indicate that SRS represents a novel candidate for anti-HIV-1/HSV microbicide development.

Ontogenetic and Seasonal Variation in the Flavonoid Composition of Sophora japonica. Cultivated in Bulgaria

Quantitative changes in the accumulation of the flavonol glycosides rutin and kaempferol 3-rutinoside and the isoflavone glycosides genistin and sophorabioside have been investigated in flowers and fruits of cultivated in Bulgaria Sophora japonica. during ontogenetic and seasonal development. A method for extraction of flavonoids with good recovery was developed (98% for rutin and 97% for kaempferol 3-rutinoside). The subsequent high-performance liquid chromatography separation of flavonoid glycosides was achieved using Hypersil ODS C18 column and UV detection. The mobile phase comprised methanol and phosphate buffer, pH 3.23, and linear gradient elution mode within 25 min was applied. Accumulation of rutin started with initiation of the flower buds, having the maximal content up to 287 mg/g (dry weight) in mid-July during the earliest stages of flower development and tended to have high levels until mid-August. A further decrease in the amount of rutin up to 44 mg/g was found proportionally with the decline of flavonoids throughout and after the flowering period. Rutin was the predominant glycoside and can account for up to 90% of flavonoid glycoside mixture in young buds, whereas sophorabioside (64.7 mg/g, calculated as rutin equivalent) and kaempferol 3-rutinoside (46.8 mg/g) dominated at later development stages of the fruits. No significant differences in flavonoid quantity between the analysis periods of two successive years were observed. This indicated clearly the ontogenetic dependence of flavonoid formation.

Radical scavenging compounds from Ethiopian medicinal plants

Various solvent fractions prepared from plants used in Ethiopian traditional medicine were examined for their potential radical scavenging activity using rapid TLC screening method. The preliminary results indicated that the methanol fractions of the leaves of Bersama abyssinica and the fronds of Cheilanthes farinose, and the acetone fraction of the leaves of Euclea racemosa ssp. schimperi possess significant free radical scavenging capacity. The abilities of these extracts to act as nonspecific donors of hydrogen atom or electrons were evaluated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. It was found out that they all showed positive results with the methanol extract of B. abyssinica (7.5 ug/ml) displaying the highest activity. Phytochemical investigation of the methanol fraction of B. abyssinica leaves resulted in the isolation of five flavonol glycosides and the xanthone, magniferin. Four flavonol glycosides together with the plant acids caffeic acid and chlorogenic acid were obtained from the methanol extract of the fronds of Cheilanthes farinose. Similarly, the acetone fraction of the browse plant, E. racemosa ssp. schimperi afforded four flavonol glycosides. All the secondary metabolites isolated from these active fractions were found to exhibit significant antioxidant activity, as judged by scavenging stable DPPH free radicals. However, the flavonol glycoside rutin figured as the most active radical scavenger with an IC50 value of 9.5 mM. Ethiopian Pharmaceutical Journal Vol. 24, 2006: 23-30

In vivo anti-inflammatory and anti-nociceptive activities of Cheilanthes farinosa

In Ethiopia inflammatory skin diseases are among the most common health problems treated with traditional remedies which mainly comprise medicinal plants. In the present work, the anti-inflammatory and anti-nociceptive activities of Cheilanthes farinosa (Forsk.) Kaulf (Adianthaceae), a fern used in many parts of Ethiopia to treat inflammatory skin disorders, were studied using in vivo models of inflammation and pain. The results of the study showed that the fronds Cheilanthes farinosa possess strong anti-inflammatory and anti-nociceptive properties. It was further demonstrated that the active ingredients of the fern reside mainly in the methanol fraction from which three compounds viz. the flavonol glycoside rutin, and the natural cinnamic acids, caffeic acid and its quinic acid derivative chlorogenic acid have been isolated. The methanol extract was also shown to potentiate the anti-inflammatory activity of acetyl salicylic acid. At the tested concentrations, the methanol extract displayed a better anti-nociceptive activity than that of ASA in both the early and late phases of formalin induced nociception in mice. However, the activity of the extract was more pronounced in the late phase, which is commonly associated with inflammatory pain. Evaluation of the pharmacological properties of the compounds isolated from the active fractions pointed out that chlorogenic acid possesses strong anti-inflammatory and anti-nociceptive activities while caffeic acid and rutin were inactive. Moreover, on molar basis chlorogenic acid was proved to be superior in its anti-inflammatory action to acetyl salicylic acid. It was therefore concluded that chlorogenic acid contributes, in full or in part, to the anti-inflammatory and anti-nociceptive activities of Cheilanthes farinosa. Both the methanolic extract and pure chlorogenic acid failed to display anti-nociceptive activity when tested by the tail-flick test indicating that the plant is not a centrally acting analgesic but instead exerts its analgesic activity by way of its antinflammtory action.

Effects of selected flavonoids and caffeic acid derivatives on hypoxanthine-xanthine oxidase-induced toxicity in cultivated human cells.

Tissue damage as a result of oxygen radical generation may be involved in the pathogenesis of different diseases, carcinogenesis, aging and cell death. The inhibition of the proliferation rate of the immortalised human cell line ECV 304 after oxidant damage by oxygen radicals generated in a hypoxanthine-xanthine oxidase system and the protection provided by some selected flavone and flavonol glycosides as well as by caffeic acid and its derivatives was determined. The cytotoxicity of the reactive oxygen species was differentially influenced by selected flavonoids and seems to be determined by the pattern of substitution and by their lipophilicity. Apigenin and quercetin demonstrated the strongest effect on the inhibition of hypoxanthine-xanthine oxidase-induced toxicity (50 % restitution of the cells at a concentration of 0.36 microM and 3.1 microM, respectively). The beneficial effect of the flavonol glycosides rutin and hyperoside was weak, whereas flavone glycosides such as diosmin showed a better effect of protection.

Intestinal absorption of rutin in free and conjugated forms

Quercetin is one of the most common flavonoids in nature, occurring mainly in glycosidic forms such as rutin. Rutin has been reported to exert numerous biochemical and pharmacological activities, though information about its absorption and metabolism is scarce. The aim of this study was to investigate intestinal handling of luminally administered rutin in an isolated preparation of luminally and vascularly perfused rat small intestine. A synthetic perfusate free from blood components was used as vascular medium, with a perfluorocarbon as oxygen carrier. Luminal media consisted of a bicarbonate-buffered sodium chloride solution spiked with rutin (40.5 ± 1.8 μmol/L). Viability was maintained during the entire perfusion; no differences between rutin and control perfusions for perfusion pressure, lactate-pyruvate ratio, oxygen uptake, and acid-base homeostasis were observed. About 10% of the administered rutin appeared at the vascular side, chiefly as free rutin (5.6%), but some rutin sulfate (2.5%) and glucuronide (2.0%) were also detected. The conjugates were preferentially absorbed to the vascular side, while only traces of the glucuronide (0.2%) were found in the luminal perfusate. Minute amounts of the rutin administered were located in the intestinal tissue (1.1%) in the form of unchanged rutin and its glucuronide and sulfate conjugates. The model used serves as a valuable tool for understanding intestinal handling of the bioactive flavonol glycoside rutin, and the obtained results confirm uptake of rutin in the rat small intestine.

The effects of low molecular weight phenolics in the ruminant gut metabolism

Polyphenolics are a common group of anti-nutritional factors, which occur in many browse plants found in the tropics. They have been implicated in the poor performance of ruminants. Detrimental effects could occur in the rumen or, if phenolics or their metabolites escape degradation, in the intestines or animal tissues. Most published reports have concentrated on examining the effect of feeding plant material containing anti-nutritional factors or the effects of administration of plant extracts containing a mixture of possible anti-nutritional compounds. We have adopted an alternative approach by investigating the metabolism of individual phenolic compounds rather than broad groups. For our initial studies the flavonol glycoside rutin (a monomeric unit of many condensed tannins) and gallic acid (monomeric unit of many hydrolysable tannins) were chosen as models to study the fate of these compounds in the rumen environment.All samples were analysed for phenolics by HPLC (Spectra Physics Focus System) using a diode-array detector (220-900nm) and a 250 × 4mm column packed with ODS Hypersil, CIS. Samples run on this system were eluted with a linear gradient of 2% glacial acetic acid(A) and methanol(B), 100% A - 100% B in 30-60 min, the gradient run time depending on the type of sample being analysed. Sample peaks were identified using their retention time, maximum absorbances and peak spectra relative to known phenolic standards. All samples containing phenolics were extracted in 100% methanol by homogenization (Polytron AG Kinematic, Switzerland) at 13,500 rpm for 2 × 90 sec. The homogenate was then centrifuged at 1·000g for 10 min. The resulting supernatant was analysed for phenolics by HPLC.

Preliminary studies on the fate of the flavonol glycoside rutin in the forestomachs of sheep

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Inhibition of insect larval growth by phenolics in glandular trichomes of tomato leaves

We have found that the foliar tetracellular glandular trichomes (tetrads) of the tomato plant,Lycopersicon esculentum Mill., contribute significantly to the antibiotic effect of the leaf against the fruitwormHeliothis zea (Boddie), as measured by reduction in larval growth. This effect is attributable to phenolic compounds localized within the tetrads. We have found that the cellular fluid of the tetrads is particularly rich in the flavonol glycoside rutin, accompanied by lesser amounts of other phenolics.

CO‐PIGMENTATION OF ANTHOCYANINS UNDER PHYSIOLOGICAL CONDITIONS

ABSTRACTComplex formation of anthocyanins with other plant constituents and the resulting color intensification enhances the possibility of their use as naturally occurring food colorants. Anthocyanins representing the four pigment groups characteristic for Vitis species, e.g. malvidin‐3‐glucoside, malvidin‐3‐p‐coumarylglucoside, malvidin‐3,5‐diglucoside and malvidin‐3‐p‐coumarylglucoside‐5‐glucoside in the concentration range 4 X 10‐6 to 4 X 10‐3 M were investigated for complex formation in the presence of the flavonol glycoside rutin (0‐2.4 X 10‐2 M). The experiments performed under conditions similar to those existing in grape juice showed a maximum color intensification of 1000% with malvidin‐3,5‐diglucoside. A 44 nm shift in the absorption maximum was observed concurrently with color intensification. The ability of the investigated anthocyanins to form deeply colored complexes with rutin decreased in the following order: malvidin‐3,5‐diglucoside (1000%), malvidin‐3‐p‐coumarylglucosid‐5‐glucoside (500%), malvidin‐3‐p‐coumarylglucoside (490%) and malvidin‐3‐glucoside (145%).