Combination Of Quercetin Research Articles

Quercetin-Induced Induction of the NO/cGMP Pathway Depends on Ca2+-Activated K+Channel-Induced Hyperpolarization-Mediated Ca2+-Entry into Cultured Human Endothelial Cells

Quercetin is one of the dietary-derived flavonoids that are held responsible for the beneficial effects of red wine drinking in coronary artery disease known as the "French paradox". We examined whether quercetin modulates endothelial function by influencing Ca2+-activated K+ channels with large conductance (BK(Ca)) in cultured human endothelial cells. Membrane potential and intracellular Ca2+ concentrations of cultured human endothelial cells derived from umbilical cord veins (HUVEC) were measured using the fluorescence dyes DiBAC, and FURA-2, respectively. NO production was examined using a cGMP radioimmunoassay. HUVEC proliferation was analyzed by cell counts and thymidine incorporation. A dose-dependent hyperpolarization of HUVEC was recorded when quercetin was added (5-100 micromol/L). The maximum effect (50 micromol/L) was significantly reduced by the addition of the highly selective BK(Ca) inhibitor iberiotoxin (100 nmol/L), but not by blockers of other Ca2+-activated K+ channels (n = 30; p < 0.05). This BK(Ca)-induced hyperpolarization caused a transmembrane Ca2+ influx, because the quercetin-induced increase of intracellular Ca2+ was blocked by iberiotoxin, or by applying 2-aminoethoxydiphenylborate (100 micromol/L)--an inhibitor of capacitative Ca2+ entry (n = 30; p < 0.05). Quercetin-induced cGMP levels were significantly reduced by the eNOS-inhibitor l-NMMA (300 micromol/L), and by iberiotoxin (n = 10; p < 0.05). Endothelial proliferation was significantly reduced by 56 % when cells were incubated with quercetin (n = 12; p < 0.05). This effect was due to the increased NO production, because it was reversed when the cells were treated with a combination of quercetin and l-NMMA. In conclusion quercetin improves endothelial dysfunction by increasing NO synthesis involving BK(Ca)-dependent membrane hyperpolarization-induced capacitative Ca 2+ entry. Increased NO production is responsible for the quercetin-dependent inhibition of endothelial proliferation.

Interactive effects of polyphenols, tocopherol and ascorbic acid on the Cu2+–mediated oxidative modification of human low density lipoproteins

Only limited knowledge is available about any interactions between phenolic compounds and other antioxidants in inhibiting LDL oxidation. Many foods and beverages contain high levels of phenolic compounds; therefore, these compounds should not be considered in isolation from each other. The aim of this study was to examine the structure-antioxidant activity relationship of quercetin, caffeic acid, epicatechin, hesperetin and phloretin as well as alpha-tocopherol and ascorbic acid through their ability to interact with copper ions. Isolated human LDL were incubated with single antioxidants or a combination of two and the kinetics of lipid peroxidation were assessed by measurement of conjugated diene formation (lag phase) via monitoring the absorbance at 234 nm after addition of copper ions. In addition, the degree of oxidation of the LDL protein moiety was followed by tryptophan fluorescence and carbonyl content measurements. Alpha-tocopherol and ascorbic acid showed a lower antioxidant activity in all test systems as compared to polyphenols at equimolar concentrations. Quercetin was the most effective compound in all three systems (p < 0.001 for lag phase and carbonyl content determination). A significant (p < 0.001) prolongation of the lag phase was found when combinations of ascorbic acid/quercetin, ascorbic acid/epicatechin, epicatechin/caffeic acid, and quercetin/epicatechin were tested as compared to the sum of the individual effects. Concerning the effects on LDL protein oxidation, the results from carbonyl content and the tryptophan fluorescence measurements showed that the combination of quercetin and caffeic acid revealed the strongest inhibitory effect (p < 0.001 carbonyl content; p < or = 0.002 tryptohan fluorescence) on protein oxidation which was higher than the effect of the single compounds. The results of the present study indicate that a combination of different antioxidants can be superior to the action of single antioxidants in protecting LDL lipid and protein moiety against oxidation. However, the substances may act by different antioxidative mechanisms, which are not necessarily complementary.

Contribution of flavonoid antioxidants to the preventive effect of mesna in cyclophosphamide-induced cystitis in rats

Cyclophosphamide (CP) is widely used, alone or in combination with other chemotherapeutic agents, for treatment of neoplastic diseases. Its urotoxicity may cause dose-limiting side-effects, for example hemorrhagic cystitis. The agent most often used to prevent this side-effect is mesna (2-mercaptoethane sulfonate). Overproduction of reactive oxygen species during inflammation is one reason for possible urothelial injury. The aim of this study was to evaluate whether combinations of quercetin and epigallocatechin 3-gallate (EGCG), flavonoid antioxidants and mesna could prevent cystitis induced by cyclophosphamide, better than mesna alone. A total of 38 male Sprague-Dawley rats were divided into five groups. Four groups received single dose of CP (100 mg kg(-1)) intraperitoneally at the same time. Group 2 received CP only, group 3 received mesna (3 x 21.5 mg kg(-1)), group 4 received a single dose of mesna+EGCG (2 x 20 mg kg(-1)), and group 5 received a single dose of mesna+quercetin (2 x 20 mg kg(-1)), before and after CP injection. Group 1 (not treated) served as control. CP injection alone resulted in severe cystitis. Mesna resulted in some, but not full, protection against CP toxicity. Quercetin and catechine, together with mesna, resulted in full protection against CP toxicity, on the basis of histopathology of the urinary bladder. It was concluded that oxidants might be important in the pathogenesis of CP-induced cystitis, and that flavonoid antioxidants, used in addition to mesna, may help to ameliorate bladder damage.

Ellagic Acid Potentiates the Effect of Quercetin on p21waf1/cip1, p53, and MAP-Kinases without Affecting Intracellular Generation of Reactive Oxygen Species In Vitro ,

Anticarcinogenic effects attributed to polyphenols in fruits may be based on synergistic, additive, or antagonistic interactions of many compounds. In a previous study, it was demonstrated that quercetin and ellagic acid interacted synergistically in the induction of apoptosis in the human leukemia cell line, MOLT-4. To investigate possible cellular mechanisms, this study evaluated whether synergistic effects might be detectable within proapoptotic or antiproliferative signal transduction pathways. We found that quercetin and combinations of quercetin and ellagic acid nonsynergistically increased p53 protein levels. In contrast, ellagic acid potentiated the effects of quercetin for p21(cip1/waf1) protein levels and p53 phosphorylation at serine 15, possibly explaining the synergistic effect observed in apoptosis induction. Phosphorylation of the mitogen-activated protein (MAP) kinases, c-jun N-terminal (JNK)1,2 and p38, was also increased by the combination of ellagic acid and quercetin, whereas quercetin alone induced only p38. We further evaluated whether the generation of reactive oxygen species (ROS) and/or quercetin stability were influenced by interactions of ellagic acid with quercetin. Quercetin increased the generation of ROS, which was neither potentiated nor inhibited by ellagic acid. The stability of intracellular and extracellular quercetin was not influenced by the presence of ellagic acid. In summary, quercetin and ellagic acid combined increase the activation of p53 and p21(cip1/waf1) and the MAP kinases, JNK1,2 and p38, in a more than additive manner, suggesting a mechanism by which quercetin and ellagic acid synergistically induce apoptosis in cancer cells.

Proteomic identification of heat shock protein 70 as a candidate target for enhancing apoptosis induced by farnesyl transferase inhibitor.

Farnesyl transferase inhibitors (FTIs) are novel antitumor drugs with clinical activity. FTIs inhibit cell growth not only by preventing direct Ras farnesylation but also through a Ras-independent pathway. Proteomics has been shown to be a powerful tool to monitor and analyze molecular networks and fluxes within the living cells and to identify the proteins that participate in these networks upon perturbation of the cellular environment. To observe early and dynamic protein changes in the cellular response to FTI in ovarian cancer cells, total proteins were extracted from 2774 cells treated or not with 10 microM manumycin, an FTI, for 3, 6 and 16 h. The proteins in the cells that were differentially expressed following treatment with manumycin for 3, 6 and 16 h were noted by two-dimensional electrophoresis and further identified by peptide mass fingerprinting as stress proteins. Both heat shock protein 70 (HSP70) and altered HSP70 were significantly up-regulated as early as 16 h in 2774 cells after exposure to manumycin. Since HSP70 plays an important role in protecting cells under stress, we treated the 2774 cells with the HSP inhibitor quercetin in combination with FTI. Quercetin dramatically enhanced the manumycin-mediated apoptosis in 2774 cells. Inducible HSP70 by manumycin in surviving ovarian cancer cells was also inhibited by quercetin as demonstrated by enzyme-linked immunosorbent assay. The inhibition of HSP70 by quercetin was correlated with enhancement of manumycin-induced mediated apoptosis in 2774 cells. The inhibition of HSP70 by 50 microM quercetin was also correlated with a decreased expression of procaspase-3 and enhancement of specific cleavage of poly (ADP-ribose) polymerase into apoptotic fragment in 2774 cells treated with manumycin. The interaction between the HSP70 inhibitor and FTI confirms the functional significance of the up-regulation of HSP70 as a protective mechanism against FTI-induced apoptosis and provides the framework for combination treatment of ovarian cancer.

Effects of Ascorbic Acid and α‐Tocopherol on Antioxidant Activity of Polyphenolic Compounds

ABSTRACTThe effects of ascorbic acid and α‐tocopherol on the antioxidant activity of 15 phenolic compounds were compared with 2 in vitro assays. Combination of ascorbic acid or α‐tocopherol plus polyphenolic compounds resulted in an additive effect as shown with DPPH–HPLC method. With the liposome oxidation method, combination of quercetin or catechins plus α‐tocopherol showed synergistic effects.

In vitro metabolism of chloroquine: identification of CYP2C8, CYP3A4, and CYP2D6 as the main isoforms catalyzing N-desethylchloroquine formation.

In humans, the antimalarial drug chloroquine (CQ) is metabolized into one major metabolite, N-desethylchloroquine (DCQ). Using human liver microsomes (HLM) and recombinant human cytochrome P450 (P450), we performed studies to identify the P450 isoform(s) involved in the N-desethylation of CQ. In HLM incubated with CQ, only DCQ could be detected. Apparent Km and Vmax values (mean +/- S.D.) for metabolite formation were 444 +/- 121 microM and 617 +/- 128 pmol/min/mg protein, respectively. In microsomes from a panel of 16 human livers phenotyped for 10 different P450 isoforms, DCQ formation was highly correlated with testosterone 6beta-hydroxylation (r = 0.80; p < 0.001), a CYP3A-mediated reaction, and CYP2C8-mediated paclitaxel alpha-hydroxylation (r = 0.82; p < 0.001). CQ N-desethylation was diminished when coincubated with quercetin (20-40% inhibition), ketoconazole, or troleandomycin (20-30% inhibition) and was strongly inhibited (80% inhibition) by a combination of ketoconazole and quercetin, which further corroborates the contribution of CYP2C8 and CYP3As. Of 10 cDNA-expressed human P450s examined, only CYP1A1, CYP2D6, CYP3A4, and CYP2C8 produced DCQ. CYP2C8 and CYP3A4 constituted low-affinity/high-capacity systems, whereas CYP2D6 was associated with higher affinity but a significantly lower capacity. This property may explain the ability of CQ to inhibit CYP2D6-mediated metabolism in vitro and in vivo. At therapeutically relevant concentrations ( approximately 100 microM CQ in the liver), CYP2C8, CYP3A4, and, to a much lesser extent, CYP2D6 are expected to account for most of the CQ N-desethylation.

Synergetic anticancer effect of combined quercetin and recombinant adenoviral vector expressing human wild-type p53, GM-CSF and B7-1 genes on hepatocellular carcinoma cells in vitro.

This study investigated the anti-cancer effect of combined quercetin and a recombinant adenovirus vector expressing the human p53, GM-CSF and B7-1 genes (designated BB-102) on human hepatocellular carcinoma (HCC) cell lines in vitro. The sensitivity of HCC cells to anticancer agents was evaluated by 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The viability of cells infected with BB-102 was determined by trypan blue exclusion. The expression levels of human wild-type p53, GM-CSF and B7-1 genes were determined by Western blot, enzyme-linked immunosorbent assay (ELISA) and flow cytometric analysis, respectively. The apoptosis of BB-102-infected or quercetin-treated HCC cells was detected by terminal deoxynucleotidyl transferase (TdT) assay or DNA ladder electrophoresis. Quercetin was found to suppress proliferation of human HCC cell lines BEL-7402, HuH-7 and HLE, with peak suppression at 50 micromol/L quercetin. BB-102 infection was also found to significantly suppress proliferation of HCC cell lines. The apoptosis of BB-102-infected HCC cells was greater in HLE and HuH-7 cells than in BEL-7402 cells. Quercetin did not affect the expression of the three exogenous genes in BB-102-infected HCC cells (P>0.05), but it was found to further decrease proliferation and promote apoptosis of BB-102-infected HCC cells. BB-102 and quercetin synergetically suppress HCC cell proliferation and induce HCC cell apoptosis, suggesting a possible use as a combined anti-cancer agent.

Food-derived polyphenols inhibit pancreatic cancer growth through mitochondrial cytochrome C release and apoptosis.

There is increasing evidence that food-derived polyphenols have a beneficial effect for cancers. Our purpose was to determine the effect and mechanism of action of these compounds on pancreatic cancer. We measured effects of quercetin on pancreatic cancer in a nude mouse model. We also investigated the effects of quercetin, rutin, trans-resveratrol and genistein on apoptosis and underlying signaling in pancreatic carcinoma cells in vitro. Quercetin decreased primary tumor growth, increased apoptosis and prevented metastasis in a model of pancreatic cancer. In vitro quercetin and trans-resveratrol, but not rutin, markedly enhanced apoptosis, causing mitochondrial depolarization and cytochrome c release followed by caspase-3 activation. In addition, the effect of a combination of quercetin and trans-resveratrol on mitochondrial cytochrome c release and caspase-3 activity was greater than the expected additive response. The inhibition of mitochondrial permeability transition prevented cytochrome c release, caspase-3 activation and apoptosis caused by polyphenols. Nuclear factor-kappa B activity was inhibited by quercetin and trans-resveratrol, but not genistein, indicating that this transcription factor is not the only mediator of the polyphenols' effects on apoptosis. The results suggest that food-derived polyphenols inhibit pancreatic cancer growth and prevent metastasis by inducing mitochondrial dysfunction, resulting in cytochrome c release, caspase activation and apoptosis.

Rutin-enhanced antibacterial activities of flavonoids against Bacillus cereus and Salmonella enteritidis.

The antibacterial activities of flavonoids were found by the paper disk method to be enhanced by combining or mixing them. The combinations of quercetin and quercitrin, quercetin and morin, and quercetin and rutin were much more active than either flavonoid alone. Although rutin did not show activity in itself, the antibacterial activities of quercetin and morin were enhanced in the presence of rutin. The antibacterial activities of flavonoids, in combination with morin and rutin, were evaluated, based on the minimum inhibition concentration (MIC) in a liquid culture, by using Salmonella enteritidis and Bacillus cereus as the test bacteria. The activities of galangin, kaempherol, myricetin and fisetin were each enhanced in the presence of rutin when S. enteritidis was used as the test bacterium. The MIC value for kaempherol was markedly decreased by the addition of rutin. Morin inhibited DNA synthesis, and this effect was promoted by rutin at a concentration of 25 microg/ml.

Influence of Quercetin on dissolution behavior and ulcerogenic activity of Indomethacin

The results of in-​vivo studies, in rats, revealed that the use of Quercetin in combination with Indomethacin highly reduced the risk of adverse reaction (gastric ulcerative effect) related to the peroral administration of the drug. Gross observations and scanning electromicrographs of the mucous membrane and superficial cells of the stomach showed that the Quercetin reduced the damage of mucosal membrane and destruction of the gastric superficial cells presented under the mucous membrane. The phys. and chem. compatibilities of a double blend of Indomethacin and Quercetin prepd. by solvent evapn. technique were confirmed using IR spectroscopy, differential scanning calorimetry and x-​ray diffractometer. Also, the results showed that the presence of Quercetin in copptd. mixt. with Indomethacin does not affect the dissoln. characteristics of the drug. The results suggest that a compatible blend from Indomethacin and Quercetin could be pharmaceutically formulated with the aim of reducing the gastrointestinal adverse effects of Indomethacin.

PRELMINARY EVALUATION OF QUERCETIN EFFECT ON DICLOFENAC SODIUM ASSOCIATED GASTRIC ULCER IN RATS.

The effect of quercetin (QRT) in preventing or reducing the diclofenac sodium-induced gastric ulcers was evaluated in rats following over night fasting by using a scanning electron microscopy. The scanning micrographs of stomach specimens showed a marked reduction in the gastric ulceration only when the quercetin is given before the administration of diclofenac sodium. The physicochemical characteristics of diclofenac sodium and quercetin combination were studied using differential scanning calorimetry, IR spectroscopy and X-ray diffractometery. The results revealed that a chemical incompatibility of diclofenac sodium and quercetin undoubtedly has been occurred when they were mixed in one combination. According to aforementioned results, we advise orally taking quercetin only before administration of diclofenac sodium as a prophylactic treatment to protect against its expected gastric disturbances.

IBUPROFEN-QUERCETIN COMBINATION ASA NOVEL PHARMACEUTICAL COMPATIBLE SYSTEM

The effect of oral administration of quercetin (QRT) (25 mg/kg) on an experimentally Ibuprofen- induced ulcer was studied in rats. The results of gross appearance and scanning electromicrographs of the mucous membrane and superficial cells of the stomach revealed that the quercetin reduced the damage of submucosal superficial cells. Differential scanning calorimetry, X-ray diffractometer, IR spectroscopy, solubility and partitioning studies elucidated the absence of any interaction between the two compounds and also the physical compatibility of ibuprofen (IP)-quercetin combination. It is concluded that ibuprofen and quercetin can be pharmaceutically co-formulated or co-administrated with the aim of reducing the gastrointestinal adverse effects of ibuprofen.

Herbals for Alzheimer's

Phytoestrogens, also known as flavonoids, are found in plants and herbal medicines. When applied to cortical neurons in culture, the flavone apigenin and the flavonol kaempferol decreased apoptosis induced in those cells by treatment with amyloid β protein (Aβ). Both flavonoids inhibited caspase activity stimulated by Aβ treatment and apigenin was also able to inhibit the release of cytochrome c . A second mechanism by which flavonoids may be neuroprotective is through their antioxidant properties. Many flavonoids were able to inhibit the increase in reactive oxygen species (ROS) produced by treatment with Aβ; however, their antioxidant activity did not correlate well with neuroprotective activity. The most effective neuroprotection was seen when cells were treated agents that could inhibit both the production of ROS and caspase activation, for example kaempferol alone was highly effective and the combination of quercetin (a strongly antioxidant flavonoid) or the nonflavonoid antioxidant probucol with apigenin was also highly effective. C.-N. Wang, C.-W. Chi, Y.-L. Lin, C.-F. Chen, Y.-J. Shiao, The neuroprotective effects of phytoestrogens on amyloid β protein-induced toxicity are mediated by abrogating the activation of caspase cascade in rat cortical neurons. J. Biol. Chem. 276 , 5287-5295 (2001). [Abstract] [Full Text]

Flavonoids of Hawaiian endemic lysimachia in honour of professor G. H. Neil Towers 75th birthday

Flavonoids of 12 of the 13 extant species of Lysimachia (Primulaceae) endemic to the Hawaiian Islands were isolated and identified. Whenever possible, at least two populations were sampled. The flavonoid profiles consisted of various combinations of kaempferol, quercetin and isorhamnetin 3-O-mono-, di- and triglycosides, vitexin and isovitexin, and eriodictyol 7-O-glucoside. Flavonol di- and triglycosides were the predominant compounds present in all of the profiles. Profiles were variable both within and among specimens such that taxon-specific patterns do not appear to exist in most cases. An exception is the finding that the three leaf forms of L. remyi subsp. remyi, the most variable taxon in the subgenus, exhibit the most coherent flavonoid pattern. Flavonoid variation is compared to other Hawaiian endemic species, e.g. Bidens. Flavonoids do not support recognition of the endemic species, currently considered to constitute subgenus Lysimachiopsis, at the generic level. The flavonoids of subgen. Lysimachiopsis have some structural features in common with each of the other subgenera for which data are available.

Interaction between the cytostatic effects of quercetin and 5-fluorouracil in two human colorectal cancer cell lines

Therapy with 5-fluorouracil (5-FU) as a single agent has only limited success in palliative treatment of cancer of the large bowel. In the current study, the effect of quercetin on the action of 5-FU in the human colorectal cancer cell lines COLO 320 DM and COLO 205 was evaluated using the MTT and clonogenic assays. Both assays were used in order to discriminate between cell growth inhibition and actual cell kill. As single agents as well as in combination, considerably higher concentrations of 5-FU and quercetin were required in the clonogenic assay to obtain detectable effects than in the MTT assay. In the MTT assay, but not in the clonogenic assay, a synergistic interaction between quercetin and 5-FU was found for COLO 320 DM cells. Our results therefore indicate that this interaction between quercetin and 5-FU mainly takes place at the level of growth inhibition. It is concluded that the cytostatic action of a combination of quercetin and 5-FU in COLO 320 DM cells is superior to that of the single agents.

Mechanism of quercetin-induced suppression and delay of heat shock gene expression and thermotolerance development in HT-29 cells.

Previous studies have shown that a combination of low pH and quercetin (QCT) treatment following heat shock markedly suppresses and delays the expression of heat shock protein genes, particularly the HSP70 gene (Lee et al., Biochem. Biophys. Res. Commun., 186:1121-1128, 1992). The possible mechanism for alteration of gene expression by treatment with QCT at low pH was investigated in human colon carcinoma cells. Cells were heated at 45 degrees C for 15 min and then incubated at 37 degrees C for various times (0-12 h) with QCT (0.05-0.2 mM) at pH 7.4 or 6.5. Gel mobility-shift analysis of whole cell extracts from heated cells showed the formation of the heat shock transcription factor (HSF)-heat shock element (HSE) complex. Dissociation of HSF from the HSE of the human HSP70 promotor occurred within 4 h under both pH conditions. The kinetics of recovery were not affected by treatment with 0.1% dimethyl sulfoxide (DMSO). However, the dissociation of HSF-HSE complex was markedly delayed during treatment with a combination of low pH and QCT. In addition, in vitro transcription assays showed a suppression of initiation and elongation of HSP70 mRNA. These results may explain why the combination of low pH and QCT treatment suppresses and delays the HSP70 gene expression as well as thermotolerance development.

The combination of quercetin and cytosine arabinoside synergistically inhibits leukemic cell growth

It has been demonstrated that quercetin (3,3′,4′,5,7-pentahydroxyflavone) inhibits the growth of several cancer cell lines and that the antiproliferative activity of this substance is probably mediated through a binding interaction with type II estrogen binding sites (type II EBS). The effect of quercetin and cytosine arabinoside (Ara-C) alone or in combination, was tested on HL-60 cell growth. Quercetin significantly synergized the inhibitory activity of Ara-C on HL-60 cell growth while rutin, the 3-rhamnosylglucoside of quercetin, neither competed with [ 3H]estradiol for type II EBS nor was effective alone or in combination with Ara-C. Based on these results, we studied by a clonogenic assay the effect of quercetin and Ara-C alone and in combination on colony formation by human leukemic cells (CFU-L). In all cases both drugs exhibited a dose-related inhibition of CFU-L in a range of concentrations between 10 nM and 10 μM and 0.01 nM and 10 μM for quercetin and Ara-C, respectively. The combination of the two drugs resulted in a synergistic inhibitory activity on CFU-L. Considering that plasma concentrations of quercetin effective in vitro were obtained in vivo without any apparent side effects, we conclude that this report represents further experimental evidence that quercetin could be used in the treatment of acute leukemias.

Inhibitory effect of quercetin on primary ovarian and endometrial cancers and synergistic activity with cis-diamminedichloroplatinum(II)

It has been demonstrated that the flavonoid quercetin (3,3′,4′,5,7-pentahydroxyflavone) inhibits the growth of several cancer cell lines and that the antiproliferative activity of this substance is mediated by so-called type II estrogen binding sites. Moreover it has been observed that quercetin enhances the antiproliferative activity of cis-diamminedichloroplatinum(II) (CDDP) and busulfan both in vitro and in vivo. We tested the effect of quercetin and its combination of CDDP on clonogenic cells of nine primary gynecological tumors (four ovarian and five endometrial tumors). Quercetin produced a dose-dependent inhibition of colony formation in a range of concentrations between 0.01 and 10 μM. The bromodeoxyuridine uptake into neoplastic specimens was evaluated immunocytochemically: quercetin at 10 μM concentration produced a clear reduction in the number of bromodeoxyuridine-labeled cells. The simultaneous treatment with quercetin and CDDP (in a range of concentration between 0.01 and 10 μM and 0.01 and 0.5 μg/ml, respectively) resulted in a marked synergistic antiproliferative activity in all cases, with a CDDP potentiation ranging from 1.5- to 30-fold. The combination of quercetin with two other chemotherapeutic agents, Adriamycin and etoposide (VP-16), did not yield any enhancement of the antiproliferative activity. Two other flavonoids tested, rutin and hesperidin, were ineffective on colony formation both alone and in combination with CDDP.

Significance of flavonoid chemistry in the Egyptian Fagonia glutinosa and F. isotricha complexes

Eleven flavonol glycosides were isolated and identified in four species belonging to the two complexes: Fagonia glutinosa and F. isotricha. The compounds show considerable diversity in glycosidic combinations of quercetin, but less variation in the glycosides of kaempferol. Four of these glycosides are newly reported in the genus Fegonia; the remaining seven compounds were previously detected in the six other complexes. The distribution pattern of flavonol glycosides among the investigated species is discussed in relation to their systematic position.