Flavonoids in the flowers of Primula officinalis

From methanolic extracts of fresh flowers of PRIMULA OFFICINALIS 19 flavonoids were isolated or detected: quercetin, luteolin, kaempferol, isorhamnetin, apigenin; quercetin 3-O-glucoside, -rutinoside, -robinobioside, -gentiobioside, -(glucosyl-(1-->2) -glucosyl-(1-->6))-glucoside, -(rhamnosyl)-robinobioside; isorhamnetin 3-O-glucoside, -rutinoside, -robinobioside, -(rhamnosyl) -robinobioside; kaempferol 3-O-rutinoside, -robinobioside; limocitrin 3-O-glucoside; 3', 4'-dihydroxyflavonglucoside. Other compounds isolated were epicatechin, epigallocatechin, and proanthocyanidin B 2.     

Identification and quantitative analysis of phenolic compounds from the dry extract of Hedera helix

A thorough investigation of phenolic constituents of commercial dry extract of Hedera helix L. (Araliaceae) was carried out. Rutin (1), kaempferol 3-O-rutinoside (2), quercetin 3-O-glucoside (isoquercitrin, 5), and kaempferol 3-O-glucoside (astragalin, 12), quercetin (10), kaempferol (11), chlorogenic acid (3), neochlorogenic acid (4), 4,5- (6) and 3,5-O-dicaffeoyl-quinic (7) acids as well as rosmarinic (13), caffeic (8), and protocatechuic (9) acids were isolated and identified by spectroscopic methods. Compounds 4, 6, 7, 12, and 13 are reported for the first time for H. helix. Six main phenolics (1 -3, 6, 7, 9) were quantified by means of HPLC and capillary electrophoresis (CE).     

Red wine alcohol promotes quercetin absorption and directs its metabolism towards isorhamnetin and tamarixetin in rat intestine in vitro

Moderate consumption of red wine has been associated with beneficial effects on human health, and this has been attributed to the flavonoid content. Factors that influence the bioavailability of this group of polyphenolic compounds are therefore important. Using the rat cannulated everted jejunal sac technique, we have investigated the effect of alcohol on the intestinal absorption of quercetin and its 3-O-glucoside from red wine. Tissue preparations were incubated in whole or dealcoholised red wine, diluted 1 : 1 with Krebs buffer for 20 min at 37 degrees C, after which the mucosa was removed and processed for HPLC analysis. Tissues exposed to red wine had significantly higher amounts of both quercetin (x 3; P < 0.001) and quercetin-3-O-glucoside (x 1.5; P < 0.01) associated with them, compared with sacs incubated in the dealcoholised equivalent. In addition, both tamarixetin (T) and isorhamnetin (I), in the mucosal tissue from sacs exposed to the whole wine, were significantly elevated approximately two fold (P < 0.05; P < 0.01, respectively). Similar results were obtained when sacs were incubated in Krebs buffer containing a mixture of pure quercetin and quercetin-3-O-glucoside with or without alcohol, and, although effects on the apparent absorption of Q and Q-3-G were not so marked, concentrations of the metabolites quercetin-3-O-glucuronide and I were significantly increased by the presence of alcohol (P < 0.01 and P < 0.001, respectively). It is therefore plausible that the moderate alcohol content of red wine contributes to its beneficial health effects in humans by both increasing the absorption of quercetin and quercetin-3-O-glucoside and by channelling their metabolism towards O-methylation to yield compounds (T and I), which have potential protective effects against cancer and cardiovascular diseases.     

红花化学成分的研究

红花为菊科植物红花（ＣａｒｔｈａｍｕｓｔｉｎｃｔｏｒｉｕｓＬ．）的干燥花，是重要的活血化瘀中药之一［１］。红花有降血压、降血脂等作用，临床上用于治疗冠心病、高血压等疾病［２］。为阐明红花的活性成分，我们曾以药理活性为指标，对其化学成分进行研究，报道...     

Polyphenolic compounds in Scopolia caucasica Kolesn. ex Kreyer (Solanaceae)

The qualitative and quantitative determinations of coumarins, phenolic acids and flavonoids in the leaves and underground parts of Scopolia caucasica using paper chromatography and HPLC methods were described. From the leaves of this plant, kaempferol 3-O-(2-glucosyl)-galactoside-7-O-glucoside, kaempferol 3-O-(2-glucosyl)-galactoside and quercetin 3-O-glucoside were isolated and identified by spectroscopic methods (UV, 1H- and 13C-NMR).     

Flavonoids from some species of genus Scopolia Jacq

Kaempferol 3-O-(2-glucosyl)-galactoside-7-O-glucoside was isolated from the leaves of Scopolia carniolica Jacq. and S. sinensis Hemsl. From the latter taxon as well as kaempferol 3-O-galactoside and 3-O-(2-glucosyl)-galactoside, kaempferol and quercetin 3-O-robinobiosides and quercetin 3-O-sophoroside have been obtained. Moreover, from the leaves of S lurida Dun. kaempferol and quercetin 3-O-glucosides and 3-O-rutinosides were isolated. The structures of compounds have been determined by means of chemical and spectral methods (UV, LSI MS, 1H and 13C NMR, 1H-1H COSY NMR).     

Cytotoxic activity of nepetin, a flavonoid from Eupatorium ballotaefolium HBK

The present study evaluated the cytotoxic activity of nepetin and quercetin-3-O-glucoside, compounds isolated from the aerial parts of Eupatorium ballotaefolium. The antimitotic activity was determined as the ability to inhibit sea urchin eggs development and five tumor cells lines growth. Moreover, the activities of these compounds were compared to quercetin in the same models. Nepetin inhibited the proliferation of the five tumor cell lines, once quercetin-3-O-glucoside did not present any activity even at the highest tested concentration and quercetin only inhibited proliferation of the B16 cell line. On the sea urchin assay, nepetin and quercetin induced a dose-dependent inhibition on egg development, while quercetin-3-O-glucoside did not modify normalegg cleavage, even at the highest tested concentration (100 microg/ml).     

Flavonoid compounds in the flowers of Kitaibelia vitifolia Willd. (Malvaceae)

The following compounds from the flowers of Kitaibelia vitifolia were isolated and identified: kaempferol 3-O-(6"-p-coumaroyl)-beta-glucoside (trans-tiliroside); quercetin and kaempferol - 3-O-beta-xylopyranosyl (1-->2)-beta-glucopyranoside (3-O-sambubioside): quercetin and kaempferol - 3-O-sambubioside-7-O-glucoside; apigenin, 7-O-sambubioside, luteolin and chrysoerioL, 7-O-xylosylglucosides also apigenin 7-O-alpha-rhamnopyranosyl (1-->2)-beta-glucopyranoside.     

Flavonoids and free phenolic acids from Phytolacca americana L. leaves

In the leaves of Phytolacca americana L. flavonoid compounds: kaempferol 3-O-beta-D-glucopyranoside, kaempferol 3-O-beta-D-xylopyranosyl (1-->2)-beta-D-glucopyranoside, kaempferol 3-O-alpha-L-rhamnopyranosyl (1-->2)-beta-D-glucopyranoside, kaempferol 3-O-diglucoside and quercetin 3-O-glucoside were identified by chemical and spectroscopic methods and using co-chromatography, phenolic acids: p-hydroxybenzoic, vanillic, synapic, p-coumaric ferulic and caffeic were also confirmed.     

Quercetin and its glycosides in the flowers of Asclepias syriaca L

The following flavonoid compounds have been isolated and identified from the flowers of Asclepiac syriaca L.: quercetin and its glycosides: 7-O-galactoside, 7-O-glucoside, 3-O-beta-D-xylopyranoside(1-->2) beta-D-galactoside and 3-O-beta-D-glucopyranoside(1-->2) beta-D-galactoside. Their structures were established by acid and enzymatic hydrolysis or H2O2 oxidation as well as spectral analysis (UV, 1H and 13C NMR).     

Seasonal variation of phenolic constituents and medicinal activities of Northern Labrador tea, Rhododendron tomentosum ssp. subarcticum, an Inuit and cree First Nations traditional medicine

Northern Labrador tea, Rhododendron tomentosum ssp. subarcticum, is one of the most commonly used medicinal plants by Inuit and other First Nations peoples of Canada. The phenolic profile and seasonal variation of this commonly used medicinal plant remains largely unknown. To assess optimal harvesting time, R. tomentosum was collected in accordance with traditional knowledge practices bimonthly throughout the snow-free summer in Iqaluit, Nunavut. The antioxidant potency was measured in a DPPH radical scavenging assay, and the anti-inflammatory activity was determined with a TNF-α production assay. The seasonal variation of phenolic content was assessed with HPLC-DAD for fifteen of the most abundant phenolic compounds; (+)-catechin, chlorogenic acid, PARA-coumaric acid, quercetin 3-O-galactoside (hyperoside), quercetin 3-O-glucoside (isoquercitrin), quercetin 3-O-rhamnoside (quercitrin), quercetin pentoside, myricetin, quercetin, 3 procyanidins, and 3 caffeic acid derivatives. The most abundant constituent was (+)-catechin, which made up 19?% of the total weight of characterized phenolics. There was significant seasonal variation in the quantity of all fifteen constituents assessed, whereas there was no seasonal variation of their total sum. The antioxidant activity was positively correlated with phenolic content and negatively correlated with daylight hours. The anti-inflammatory activity was negatively correlated with caffeic acid derivative 1 and daylight hours. Together these results demonstrate that the timing of harvest of R. tomentosum impacts the plant's phenolic content and its antioxidant and anti-inflammatory activities.     

A physiologically based kinetic (PBK) model describing plasma concentrations of quercetin and its metabolites in rats

Biological activities of flavonoids in vivo are ultimately dependent on the systemic bioavailability of the aglycones as well as their metabolites. In the present study, a physiologically based kinetic (PBK) model was developed to predict plasma concentrations of the flavonoid quercetin and its metabolites and to tentatively identify the regiospecificity of the major circulating metabolites. The model was developed based on in vitro metabolic parameters and by fitting kinetic parameters to literature available in vivo data. Both exposure to quercetin aglycone and to quercetin-4′-O-glucoside, for which in vivo data were available, were simulated. The predicted plasma concentrations of different metabolites adequately matched literature reported plasma concentrations of these metabolites in rats exposed to 4′-O-glucoside. The bioavailability of aglycone was predicted to be very low ranging from 0.004%-0.1% at different oral doses of quercetin or quercetin-4′-O-glucoside. Glucuronidation was a crucial pathway that limited the bioavailability of the aglycone, with 95–99% of the dose being converted to monoglucuronides within 1.5–2.5 h at different dose levels ranging from 0.1 to 50 mg/kg bw quercetin or quercetin-4′-O-glucoside. The fast metabolic conversion to monoglucuronides allowed these metabolites to further conjugate to di- and tri-conjugates. The regiospecificity of major circulating metabolites was observed to be dose-dependent. As we still lack in vivo kinetic data for many flavonoids, the developed model has a great potential to be used as a platform to build PBK models for other flavonoids as well as to predict the kinetics of flavonoids in humans.     

Structure-activity relationships of the inhibitory effects of flavonoids on P-glycoprotein-mediated transport in KB-C2 cells

We studied the effects of flavonoids, naringenin (flavanone), baicalein (flavone), kaempferol, quercetin, myricetin, morin, and fisetin (flavonols) as well as two glycosides of quercetin on P-glycoprotein (P-gp) function in multidrug-resistant P-gp overexpressing KB-C2 cells. Flavonoids such as kaempferol and quercetin increased the accumulation of rhodamine-123 dependent on their chemical structure. Analysis by flow cytometry indicated that the increase in substrate accumulation was due to the inhibition of substrate efflux. Naringenin, which lacks the 2,3-double bond in the C ring, had no effect, although it was more hydrophobic than myricetin, fisetin and morin. Therefore, the planar structure of the flavonoids seemed to be important for their interaction with P-gp. The effects of other flavonoids on the accumulation of daunorubicin were in the order of kaempferol>quercetin, baicalein>myricetin>fisetin, morin. Quercetin-3-O-glucoside and rutin had no effect. The order of the effects corresponded with that of the partition coefficients. Difference in the number and position of hydroxyl groups in flavonoid molecules by themselves seemed to have little effect. These results suggested that hydrophobicity as well as planar structure is important for the inhibitory effects of flavonoids on P-gp-mediated transport.     

山楂叶化学成分研究

目的　研究山楂(CrataeguspinnatifidaBge .varmajorN .E .Br.)叶中的化学成分。方法　用大孔树脂柱色谱、硅胶柱色谱和聚酰胺柱色谱等技术进行分离纯化,根据理化性质和光谱数据进行结构鉴定。结果　得到8个化合物,分别为山楂素I(1) ,槲皮素(2 ) ,3-O-β-D-吡喃葡糖槲皮素(3) ,3-O-β-D-吡喃半乳糖槲皮素(4) ,3-O-β-D-吡喃葡糖(6→1)-α-L-鼠李糖槲皮素(5 ) ,3-O-β-D-吡喃半乳糖(6→1)-α-L-鼠李糖槲皮素(6 ) ,山萘酚(7) ,7-O-α-L-鼠李糖-3-O-β-D-葡糖山萘酚(8)。结论　1为新化合物,8为首次从该属中分得     

A new acylated flavonoid glycoside from the flowers of Camellia nitidissima and its effect on the induction of apoptosis in human lymphoma U937 cells

From the EtOH extract of the flowers of Camellia nitidissima Chi, a new acylated flavonoid glycoside, quercetin 7-O-(6″-O-E-caffeoyl)-β-d-glucopyranoside (1), has been isolated, together with three known flavonoids: quercetin (2), quercetin 3-O-β-d-glucopyranoside (3), and quercetin 7-O-β-d-glucopyranoside (4). Their structures were elucidated on the basis of spectroscopic analysis. Compound 1 was shown to inhibit proliferation and to induce apoptosis of human lymphoma U937 cells.     

Effects of quercetin and quercetin-3-O-glycosides on oxidative damage in rat C6 glioma cells

Flavonoids are reported to be powerful antioxidants in cell free systems. They naturally occur as glycosides rather than as aglycon. In this study the ability of the flavonoid quercetin and its glycosides, quercetin-3-O-rutinoside (rutin), quercetin-3-O-glucoside and quercetin-3-O-(6″-O-acetyl)-glucoside, to protect in vitro rat C6 glioma cells from oxidative damage induced by cumene hydroperoxide was investigated. Cumene hydroperoxide induced cell death and lipid peroxidation. The cytotoxicity of cumene hydroperoxide could be prevented by the radical scavenger dimethyl thiourea and the ferric iron chelator deferoxamine, indicating that its cytotoxic activity is related to the generation of reactive oxygen radicals in the ferrous iron dependent Fenton reaction. Quercetin, in a concentration range of 10-100 μM, but neither rutin nor the other two glycosides, were able to protect C6 cells from cytotoxicity and lipid peroxidation. Furthermore, cytoprotective concentrations of quercetin proved to be cytotoxic itself. These results call in question potential beneficial effects of dietary intake or therapeutic use of naturally occurring flavonoids.     

Radical scavenging and xanthine oxidase inhibitory activity of phenolic compounds from Bridelia ferruginea stem bark

Bridelia ferruginea Benth. (Euphorbiaceae) is a subtropical medicinal plant widely used in traditional African medicine against various diseases, including rheumatic pains. Seven of its constituents (3-O-methylquercetin (1), 3,7,3',4'-tetra-O-methylquercetin (rutisin, 2), myricetin (3), 3',4',5'-tri-O-methylmyricetin (ferrugin, 4), 3,3',4',5'-tetra-O-methylmyricetin (5), quercetin 3-O-glucoside (6), and a biflavanol gallocatechin-[4'-O-7]-epigallocatechin (7)) have been evaluated in-vitro in the xanthine-xanthine oxidase enzymatic system for inhibition of xanthine oxidase and radical scavenging activity. Results indicated that compounds 1, 3, 4 and 6 exhibited, at different levels, xanthine oxidase inhibiting and superoxide scavenging activity at micromolar concentrations, whereas compound 7 showed scavenging activity only. Compounds 2 and 5 were inactive in both cases. Study of the structure-activity relationship demonstrated that for flavonoids the xanthine oxidase inhibitory activity was reduced by methylation of the hydroxyl functionality at C-3 and in rings A and B. These results may partly explain and support the use of B. ferruginea stem bark for the treatment of rheumatic pains in traditional medicine.     

高效液相-质谱串联方法快速测定大鼠血浆中的槲皮素-3’-O-葡萄糖苷含量(英文)

建立大鼠血浆中槲皮素-3’-O-葡萄糖苷的高效液相-串联质谱(HPLC-MS/MS)检测法。生物样品中槲皮素-3’-O-葡萄糖苷和卡马西平(内标)采用液-液萃取的方法提取,乙酸乙酯作为提取溶剂。HPLC-MS/MS方法采用多离子反应模式(MRM)进行检测,被测物质和内标均在3.5min内出峰。槲皮素-3’-O-葡萄糖苷在血浆中的最低定量限是10.625ng/mL,最低检测限是4.25ng/mL,平均回收率大于66.80%,日内、日间精密度和准确度的RSD值均小于10.44%。尾静脉注射10mg/kg槲皮素-3’-O-葡萄糖苷后,其t1/2和AUC分别是(0.02±0.01)h和(1.22±0.28)×104μg/L·h。本法准确、稳定、灵敏度高,适用于槲皮素-3’-O-葡萄糖苷的大鼠药代动力学研究。     

Anticomplement and antioxidant activities of new acetylated flavonoid glycosides from Centaurium spicatum

In addition to the three acetylated flavonol glycosides, quercetin 3- O-[(2,3,4-triacetyl-alpha-rhamnopyranosyl)-(1-->6)]-beta-galactopyranoside, quercetin 3- O-[(2,3,4-triacetyl-alpha-rhamnopyranosyl)-(1-->6)]-3-acetyl-beta-galactopyranoside, and quercetin 3- O-[(2,3,4- triacetyl-alpha-rhamnopyranosyl)-(1-->6)]-4-acetyl-beta-galactopyranoside, which have recently been isolated from Centaurium spicatum (L.) Fritsch (Gentianaceae), a new pentaacetylated flavonoid glycoside was isolated from the same plant. Structure elucidation, especially the localization of the acetyl groups, and complete (1)H- and (13)C-NMR assignments, was carried out using one- and two-dimensional NMR methods, including (1)H- and (13)C-NMR, DEPT-135 and DEPT-90, and gradient-assisted experiments such as DQF-COSY, TOCSY, HSQC and HMBC. The structure of the new flavonoid glycoside was established as quercetin 3- O-[(2,3,4-triacetyl-alpha-rhamnopyranosyl)-(1-->6)]-3,4-diacetyl-beta-galactopyranoside. The anticomplement and antioxidant activities of these compounds were evaluated. The triacetylated flavonoid glycoside showed the highest activity in the two assays.     

Polygoacetophenoside, A New Acetophenone Glucoside from Polygonum multiflorum1

Polygoacetophenoside ( 3), a new acetophenone glucoside, was isolated from POLYGONUM MULTIFLORUM (Polygonaceae), together with quercetin 3- O-galactoside ( 1) and arabinoside ( 2). The structure of the new glucoside was deduced to be 2,3,4,6-tetrahy-droxyacetophenone 3- O-beta- D-glucoside ( 3) by its chemical and spectral data.