Tetralones and flavonoids from Pyrola calliantha

Two new tetralones, pyrolones A (1) and B (2), and a new flavonol glycoside, 2'-O-(4-hydroxybenzoyl)hyperin (3), were isolated from Pyrola calliantha (whole plant), together with six structurally related compounds, including 2'-O-galloylhyperin (4), hyperin (5), formononetin (6), quercetin 3-O-alpha-L-arabinopyranoside (7), quercetin 3-O-alpha-L-arabinofuranoside (8), and kaempferol 3-O-beta-D-galactopyranoside (9). The structures and absolute configurations of the new compounds were elucidated on the basis of spectroscopic (UV, ORD, CD, NMR) and mass-spectrometric (HR-ESI-MS) analyses.     

金花茶花化学成分的研究

采用反复硅胶柱色谱法、Sephadex LH-20柱色谱法、ODS柱色谱法、反复重结晶等方法对金花茶花的化学成分进行分离纯化,并通过理化常数测定和波谱分析等方法进行结构鉴定.从金花茶花的乙醇提取物中分离得到13个化合物,分别鉴定为:槲皮素(1)、槲皮素-7-O-β-D-葡萄糖苷(2)、槲皮素-3-O-β-D-葡萄糖苷(...     

虎尾草化学成分研究

从虎尾草Lysimachia barystachys地上部分中分得8个已知黄酮苷类化合物,通过波谱解析其结构分别鉴定为槲皮素(1),山奈酚(2),金丝桃苷(3)、芦丁(4)、3,5,7,3',4'-五羟基黄酮-3-O-(2,6-二-O-α-L-吡喃鼠李糖)-β-D-吡喃半乳糖苷(5),3,5,7,3',4'-五羟基黄酮-7-O-α-L-吡喃鼠李糖-3-O-α-L-吡喃鼠李糖(1-2)-β-D-吡喃葡萄糖苷(6),3,5,7,4'-四羟基黄酮-3-O-(2,6-二-O-α-L-吡喃鼠李糖)-β-D-吡喃半乳糖苷(7),3,5,7,4'-四羟基黄酮-7-O-α-L-吡喃鼠李糖-3-O-α-L-吡喃鼠李糖(1-2)-β-D-吡喃葡萄糖苷(8).这些化合物除3,4外均为首次从该植物中分离得到.     

A new kaempferol triglycoside from Fagonia taeckholmiana: cytotoxic activity of its extracts

In addition to apigenin, apigenin 7-O-glucoside, kaempferol 3-O-glucoside, kaempferol 3,7-di-O-rhamnoside, quercetin, and quercetin 3-O-glucoside, the methanolic extract of Fagonia taeckholmiana afforded a new compound identified as kaempferol 3-O-beta-l-arabinopyranosyl-(1-->4)-alpha-l-rhamnopyranoside-7-O-alpha-l-rhamnopyranoside. Identification of the isolated compounds was based on chemical and spectroscopic analyses including UV, FABMS, (1)H, (13)C and 2D NMR, and DEPT. The cytotoxic activities of the compounds against several cancer cell lines were determined.     

Comparative mutagenesis of plant flavonoids in microbial systems.

The plant flavonoids quercetin (3,5,7,3',4'-pentahydroxyflavone), morin (3,5,7,2',4'-pentahydroxyflavone), kaempferol (3,5,7,4'-tetrahydroxyflavone), chrysin (5,7-dihydroxyflavone), fisetin (3,7,3',4'-tetrahydroxyflavone), myricetin (3,5,7,3',4',5'-hexahydroxyflavone), myricitrin (myricetin-3-rhamnoside), hesperetin (3',5,7-trihydroxy-4'-methoxyflavanone), quercitrin (quercetin-3-L-rhamnoside), rutin (quercetin-3-rhamnosylglucoside or quercetin-3-rutinoside), and hesperidin (hesperetin-7-rutinoside) have been assayed for mutagenicity in the Salmonella/microsomal activation system. Quercetin, morin, kaempferol, fisetin, myricetin, quercitrin and rutin were mutagenic in the histidine reversion system with the frameshift strain TA98. The flavonols quercetin and myricetin are mutagenic without metabolic activation, although more effective when a rat liver microsomal preparation (S-9) is included; all others require metabolic activation. Flavonoids are common constituents of higher plants, with extensive medical uses. In addition to pure compounds, we have examined crude extracts of tobacco (snuff) and extracts from commonly available nutritional supplements containing rutin. Mutagenic activity can be detected and is correlated with the flavonoid content.     

Protective effects of quercetin and its metabolites on H2O2-induced chromosomal damage to WIL2-NS cells

We investigated chromosomal damage caused by a typical flavonoid, quercetin, and its two conjugates, quercetin-3-O-sulfate and isorhamnetin, and their protective effects against chromosomal damage induced by H2O2. The chromosomal damage was detected by the cytokinesis-block micronucleus (CBMN) assay using a lymphoblastoid cell line, WIL2-NS. We found that quercetin itself induced chromosomal damage at 10 microM, but quercetin-3-O-sulfate and isorhamnetin did not induce damage up to 30 microM. In the medium used for the CBMN assay, quercetin (at 100 microM) generated a high concentration of H2O2, but the two conjugates did not at the same concentration. On the other hand, pretreatment with quercetin (at 1 microM), quercetin-3-O-sulfate (at 10 microM), and isorhamnetin (at 5 microM) prevented H2O2-induced chromosomal damage to WIL2-NS cells. These findings suggest that the induction and prevention of H2O2-induced chromosomal damage are different between quercetin and its metabolites.     

Characterisation of the phenolic profile of Boerhaavia diffusa L. by HPLC-PAD-MS/MS as a tool for quality control

Phenolic acids and flavonols of nine leaf and three root samples of Boerhaavia diffusa L., collected at different locations and subjected to several drying procedures, were characterised by reversed-phase HPLC-PAD-ESI/MS for the first time. Ten phenolic compounds were identified: 3,4-dihydroxy-5-methoxycinnamoyl-rhamnoside, quercetin 3-O-rhamnosyl(1-->6)galactoside (quercetin 3-O-robinobioside), quercetin 3-O-(2"-rhamnosyl)-robinobioside, kaempferol 3-O-(2"-rhamnosyl)-robinobioside, 3,5,4'-trihydroxy-6,7-dimethoxyflavone 3-O-galactosyl(1-->2)glucoside [eupalitin 3-O-galactosyl(1-->2)glucoside], caffeoyltartaric acid, kaempferol 3-O-robinobioside, eupalitin 3-O-galactoside, quercetin and kaempferol. Quantification was achieved by HPLC-PAD and two phenolic patterns were found for the leaves, in which quercetin 3-O-robinobioside or quercetin 3-O-(2"-rhamnosyl)-robinobioside was the major compound. Caffeoyltartaric acid was only present in the root material where it represented the main phenolic constituent. The results obtained demonstrated that the geographical origin (particularly the nature of the soil), but not the drying process, influences the phenolic composition.     

Taxodione, a DNA-binding compound from Taxodium distichum L. (Rich.)

8-beta-Hydroxypimar-15-en-19-oic acid (1), taxodione (2), 6,7-dehydro-8-hydrotaxodone (3), quercetin-3-O-beta-D-glucopyranoside (4), and shikimic acid (5) were isolated from the leaves of Taxodium distichum L. (Rich.) for the first time. Previously reported compounds [beta-sitosterol (6), isorhamnetin (7), quercetin (8), isorhamnetin-3-O-alpha-arabinofuranoside (9), quercetin-3-O-a-arabinofuranoside (10)] have also been isolated. The activity of taxodione as an inhibitor for hepatic stellate cells was determined. The antitumour activity of 2, 3, and 5 using a DNA affinity probe was examined.     

A new tropane alkaloid and other constituents of Erythroxylum rimosum (Erythroxylaceae)

A new tropane alkaloid, named the 7β-acetoxy-3β,6β-dibenzoyloxytropane (1), was isolated from a methanol extract of Erythroxylum rimosum O.E. Schulz leaves. Other known compounds were detected, including quercetin, kaempferol-3-O-α-l-arabinofuranoside, (+)-catechin, epicatechin, quercetin-3-O-α-arabinofuranoside, quercetin-3-O-α-arabinopyranoside, quercetin-3-O-β-arabinopyranoside, quercetin-3-β-glucopyranoside, kaempferol, quercetin-3-O-β-galactopyranoside, β-sitosterol, α-amyrin, β-amyrin, and the ester derivatives of these two amyrins. Compound 1 exhibited weak inhibition of acetylcholinesterase. Structural identification was performed using IR, ESIHRMS and one- and two-dimensional NMR data analyses and confirmed by comparison with literature data.     

The antileishmanial activity assessment of unusual flavonoids from Kalanchoe pinnata

The importance of flavonoids for the antileishmanial activity of Kalanchoe pinnata was previously demonstrated by the isolation of quercitrin, a potent antileishmanial flavonoid. In the present study, the aqueous leaf extract from the medicinal plant K. pinnata (Crassulaceae) afforded a kaempferol di-glycoside, named kapinnatoside, identified as kaempferol 3-O-alpha-L-arabinopyranosyl (1-->2) alpha-L-rhamnopyranoside (1). In addition, two unusual flavonol and flavone glycosides already reported, quercetin 3-O-alpha-L-arabinopyranosyl (1-->2) alpha-L-rhamnopyranoside (2) and 4',5-dihydroxy-3',8-dimethoxyflavone 7-O-beta-D-glucopyranoside (3), have been isolated. Their structures were determined via analyses of mono and bi-dimensional (1)H and (13)C NMR spectroscopic experiments and HR-MALDI mass spectra. Because of its restricted occurrence and its abundance in K. pinnata, flavonoid (2) may be a chemical marker for this plant species of high therapeutic potential. The three flavonoids were tested separately against Leishmania amazonenis amastigotes in comparison with quercitrin, quercetin and afzelin. The quercetin aglycone - type structure, as well as a rhamnosyl unit linked at C-3, seem to be important for antileishmanial activity.     

Anaerobic degradation of flavonoids by Clostridium orbiscindens

An anaerobic, quercetin-degrading bacterium was isolated from human feces and identified as Clostridium orbiscindens by comparative 16S rRNA gene sequence analysis. The organism was tested for its ability to transform several flavonoids. The isolated C. orbiscindens strain converted quercetin and taxifolin to 3,4-dihydroxyphenylacetic acid; luteolin and eriodictyol to 3-(3,4-dihydroxyphenyl)propionic acid; and apigenin, naringenin, and phloretin to 3-(4-hydroxyphenyl)propionic acid, respectively. Genistein and daidzein were not utilized. The glycosidic bonds of luteolin-3-glucoside, luteolin-5-glucoside, naringenin-7-neohesperidoside (naringin), quercetin-3-glucoside, quercetin-3-rutinoside (rutin), and phloretin-2'-glucoside were not cleaved. Based on the intermediates and products detected, pathways for the degradation of the flavonol quercetin and the flavones apigenin and luteolin are proposed. To investigate the numerical importance of C. orbiscindens in the human intestinal tract, a species-specific oligonucleotide probe was designed and tested for its specificity. Application of the probe to fecal samples from 10 human subjects proved the presence of C. orbiscindens in 8 out of the 10 samples tested. The numbers ranged from 1.87 x 10(8) to 2.50 x 10(9) cells g of fecal dry mass(-1), corresponding to a mean count of 4.40 x 10(8) cells g of dry feces(-1).     

Three new benzophenone glycosides with MAO-A inhibitory activity from Hypericum thasium Griseb.

Purification of n-BuOH fraction from 80% ethanol extract of Hypericum thasium Griseb. resulted in the isolation of three new compounds 3′,4,5′-trihydroxy-6-methoxy-2-O-α-l-arabinosylbenzophenone (1), 3′,4,5′,6-tetrahydroxy-2-O-α-l-arabinosylbenzophenone (2), and 3′,4-dihydroxy-5′-methoxy-2-O-α-l-arabinosyl-6-O-β-d-xylosylbenzophenone (3) along with a known flavonoid glycoside quercetin-3-O-α-l-arabinofuranoside (4). The structures of the new compounds were elucidated by 1D and 2D NMR analysis as well as HRESIMS. The isolated compounds (1–4), as well as quercetin, and kaempferol previously isolated from EtOAc fraction were screened against MAO-A inhibitory activity. When tested against the MAO-A quercetin and kaempferol displayed IC₅₀ values of 19.6, and 17.5 μM, respectively. The IC₅₀ values for MAO-A inhibition by compounds (1–4) were 310.3, 111.2, 726.0, and 534.1 μM, respectively. Standard inhibitor (clorgyline) exhibited MAO-A inhibition with an IC₅₀ value of 0.5 μM.     

Flavonol glycosides of Warburgia ugandensis leaves

Four new flavonol gycosides: kaempferide 3-O-beta-xylosyl (1-->2)-beta-glucoside, kaempferol 3-O-alpha-rhamnoside-7,4'-di-O-beta-galactoside, kaempferol 3,7,4'-tri-O-beta-glucoside and quercetin 3-O-[alpha-rhamnosyl (1-->6)] [beta-glucosyl (1-->2)]-beta-glucoside-7-O-alpha-rhamnoside, were characterized from a methanolic leaf extract of Warburgia ugandensis. The known flavonols: kaempferol, kaempferol 3-rhamnoside, kaempferol 3-rutinoside, myricetin, quercetin 3-rhamnoside, kaempferol 3-arabinoside, quercetin 3-glucoside, quercetin, kaempferol 3-rhamnoside-4'-galactoside, myricetin 3-galactoside and kaempferol 3-glucoside were also isolated. Structures were established by spectroscopic and chemical methods and by comparison with authentic samples.     

Flavonoid glucuronides with anti-leukaemic activity from Polygonum amphibium L

Introduction –  The chemical and pharmaceutical studies carried out on species from Polygonum L. genus showed biological activity both of the extracts and the components isolated from them. These results were the impulse to examine Polygonum amphibium L. Objective –  The aim of this study was the isolation of active components from methanol extract and the determination of their cytotoxic effect on human leukaemic cell lines. Methodology  – Three flavonoid components from butanol soluble fractions of methanol extract by CC and PC preparative chromatography were isolated. Their structures were established on the basis of ¹H, ¹³C and correlation (DEPT, H‐H, COSY, HMQC, HMBC) NMR, UV and FAB‐MS spectroscopic techniques. The evaluation of the anti‐leukaemic activities of 1 and 2 against Jurkat and HL60 cell lines was carried out in vitro using annexin V fluorescence assay. Results  – Two new flavonoid glucuronides, quercetin‐3‐O‐β‐glucuronide ( 1 ) and quercetin‐3‐O‐α‐rhamnosyl‐(1 → 2)‐β‐glucuronide ( 2 ), and kaempferol‐3‐O‐α‐rhamnosyl‐(1 → 2)‐β‐glucuronide ( 3 ), were isolated from Polygonum amphibium L. It was demonstrated that the glucuronides of quercetin are able to induce apoptosis in the tested human leukaemic cells. These compounds penetrate through cytoplasm to the cellular nucleus of the cultured cells, and give intensive apoptotic responses in the stimulated leukaemic cells. The number of apoptotic cells increased with the concentration (1 nm to 10 µm ) of 1 or 2 and periods of exposure (1–3 days). Conclusion  – Compounds 1 and 2 may be considered good candidates for leukaemia chemotherapeutic agents. Copyright © 2008 John Wiley & Sons, Ltd.     

Chemical Constituents from Fruits of Rosa davidii

From the fruit of Rosa davidii Crep., eleven compounds were isolated and identified by spectral evidence, viz. 2α,3β,19β-trihydroxyl-olean-12-en-28-oic acid (1), 2α,3β-dihydroxyl-urs-28(13)-lactone (2), arjunic acid (3), euscaphic acid (4), 2α,3β-dihydroxyl-urs-12-en-28-oic acid (5), oleanolic acid (6), kaempferol (7), tiliroside (8), quercetin (9), daucosterol (10) and β-sitosterol (11). Among them, 1 and 2 were new compounds.     

Isoflavonoid glycosides and rotenoids from Pongamia pinnata leaves

Chromatographic separation of a 70% aqueous methanol extract (AME) of Pongamia pinnata (Linn.) Pierre (Leguminosae) leaves has led to the isolation of two new isoflavonoid diglycosides, 4'-O-methyl-genistein 7-O-beta-D-rutinoside (2) and 2',5'-dimethoxy-genistein 7-O-beta-D-apiofuranosyl-(1"'-->6")-O-beta-D-glucopyranoside (6), and a new rotenoid, 12a-hydroxy-alpha-toxicarol (5), together with nine known metabolites, vecinin-2 (1), kaempferol 3-O-beta-D-rutinoside (3), rutin (4), vitexin (7), isoquercitrin (8), kaempferol 3-O-beta-D-glucopyranoside (9), 11,12a-dihydroxy-munduserone (10), kaempferol (11), and quercetin (12). Their structures were elucidated on the basis of chemical and spectroscopic analyses.     

Effect of quercetin conjugates on vascular permeability and expression of adhesion molecules

Quercetin and its glucosides exist in plant foods and are recovered in human plasma as glucuronide and sulfate conjugates. Quercetin and its conjugates show antioxidant activity in model experiments. It remains obscure, however, whether these conjugates retain these biological functions in vivo. We investigated the interaction of quercetin conjugates with lipid bilayers using liposome systems. Less quercetin conjugate was incorporated into liposomes than quercetin aglycone. We also studied the vascular permeability of quercetin-3-glucuronide using cell culture inserts. Incubation of human aortic endothelial cells (HAECs) with IL-1alpha resulted in increased permeability of quercetin-3-glucuronide. Furthermore, quercetin-3-glucuronide showed no suppressive effect on TNF-alpha-induced cell expression of intercellular adhesion molecule-1 (ICAM-1) on HAECs. These observations suggest that circulating conjugates of quercetin pass through the endothelium to reach vascular smooth muscle cells and exert their biological effects in the blood vessels during inflammation followed by deconjugation of the conjugates.     

Properties of quercetin conjugates: modulation of LDL oxidation and binding to human serum albumin

Quercetin is an important dietary flavonoid with in vitro antioxidant activity. However, it is found in human plasma as conjugates with glucuronic acid, sulfate or methyl groups, with no significant amounts of free quercetin present. The antioxidant properties of the conjugates found in vivo and their binding to serum albumin are unknown, but essential for understanding possible actions of quercetin in vivo. We, therefore, tested the most abundant human plasma quercetin conjugates, quercetin-3-glucuronide, quercetin-3'-sulfate and isorhamnetin-3-glucuronide, for their ability to inhibit Cu(II)-induced oxidation of human low density lipoprotein and to bind to human albumin, in comparison to free flavonoids and other quercetin conjugates. LDL oxidation lag time was increased by up to four times by low (<2 microM) concentrations of quercetin-3-glucuronide, but was unaffected by equivalent concentrations of quercetin-3'-sulfate and isorhamnetin-3-glucuronide. In general, the compounds under study prolonged the lag time of copper-induced LDL oxidation in the order: quercetin-7-glucuronide > quercetin > quercetin-3-glucuronide = quercetin-3-glucoside > catechin > quercetin-4'-glucuronide > isorhamnetin-3-glucuronide > quercetin-3'-sulfate. Thus the proposed products of small intestine metabolism (quercetin-7-glucuronide, quercetin-3-glucuronide) are more efficient antioxidants than subsequent liver metabolites (isorhamnetin-3-glucuronide, quercetin-3'-sulfate). Albumin-bound conjugates retained their property of protecting LDL from oxidation, although the order of efficacy was altered (quercetin-3'-sulfate > quercetin-7-glucuronide > quercetin-3-glucuronide > quercetin-4'-glucuronide = isorahmnetin-3-glucuronide). Kq values (concentration required to achieve 50% quenching) for albumin binding, as assessed by fluorescence quenching of Trp214, were as follows: quercetin-3'-sulfate (approximately 4 microM)= quercetin > or = quercetin-7-glucuronide > quercetin-3-glucuronide = quercetin-3-glucoside > isorhamnetin-3-glucuronide > quercetin-4'-glucuronide (approximately 20 microM). The data show that flavonoid intestinal and hepatic metabolism have profound effects on ability to inhibit LDL oxidation and a lesser but significant effect on binding to serum albumin.     

Characterisation of new oligoglycosidic compounds in two Chinese medicinal herbs

A series of caffeic acid derivatives (3,5-dicaffeoyl-quinic acid, 3,4-dicaffeoyl-quinic acid, and 4,5-dicaffeoyl-quinic acid), and the new compound beta,3,4-trihydroxyphenethyl-O-[beta-apiofuranosyl-(1-->4)-alpha- rhamnopyranosyl-(1-->3)]-(4-O-caffeoyl)-beta-glucopyranoside (wedelosin), as well as three known flavonoid glycosides (quercetin 3-O-beta-glucoside, kaempferol 3-O-beta-apiosyl-(1-2)-beta-glucoside, and astragalin or kaempferol 3-O-beta-glucoside) were isolated from the Chinese medicinal herb Wedelia chinensis. Wedelosin showed an inhibitory activity on both the classical and the alternative activation pathway of the complement system. Another Chinese medicinal herb, Kyllinga brevifolia, yielded two known flavonoid glycosides [kaempferol 3-O-beta-apiosyl-(1-2)-beta-glucoside and isorhamnetin 3-O-beta-apiosyl-(1-2)-beta-glucoside], and a new quercetin triglycoside [quercetin 3-O-beta-apiofuranosyl-(1-->2)-beta-glucopyranoside 7-O-alpha-rhamnopyranoside]. The latter compound showed a moderate anti-viral activity.     

Phenolic derivatives from Ruprechtia polystachya and their inhibitory activities on the glucose-6-phosphatase system

Two new compounds, 5-methyl-2-(2-methylbutanoyl)phloroglucinol 1-O-(6-O-β-D-apiofuranosyl)-β-D-glucopyranoside (1) and trans-2,3-dihydrokaempferol 3-O-(4-O-sulfo)-α-L-arabinopyranoside (2), together with 14 known flavonoids, trans-dihydrokaempferol 3-O-α-L-arabinopyranoside (3), trans-taxifolin 3-O-α-L-arabinofuranoside (4), quercetin 3-O-α-L-rhamnopyranoside (5), quercetin 3'-O-α-L-arabinofuranoside (6), catechin 3-O-α-L-rhamnopyranoside (7), trans-taxifolin 3-O-α-L-arabinopyranoside (8), cis-dihydrokaempferol 3-O-α-L-arabinopyranoside (9), catechin (10), myricetin 3-O-α-L-rhamnopyranoside (11), quercetin 3-O-α-L-arabinopyranoside (12), quercetin 3-O-α-L-arabinofuranoside (13), quercetin 3-O-(3″-galloyl)-α-L-rhamnopyranoside (14), quercetin 3-O-(2″-galloyl)-α-L-rhamnopyranoside (15), and epicatechin 3-O-gallate (16), were isolated from the leaves of Ruprechtia polystachya Griseb. (Polygonaceae). Their structures were established on the basis of extensive 1D- and 2D-NMR experiments as well as MS analyses. All compounds, except 1, showed inhibition of the enzyme glucose-6-phosphatase in intact microsomes.