Quercitrin

Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer.[Pubmed: 25193878]

Arch Med Res. 2014 Aug;45(6):445-54.

Quercitrin (QR; quercetin-3-O-rhamnoside) has been used previously as an antibacterial agent and has been shown to inhibit the oxidation of low-density lipoproteins and prevent an allergic reaction. Furthermore, it was demonstrated that Quercitrin exerts protective effects against H2O2-induced dysfunction in lung fibroblast cells. However, the mechanisms of Quercitrin effects on cancer cell proliferation and apoptosis is not well understood. The aim of this study is to investigate the cytotoxic and apoptotic effects of Quercitrin and the molecular mechanisms of Quercitrin-induced apoptosis in non-small cell lung cancer (NSCLC) cell lines.
METHODS AND RESULTS:
Time- and dose-dependent antiproliferative and apoptotic effects of Quercitrin determined by WST-1 cell proliferation assay, lactate dehydrogenase (LDH) cytotoxicity assay, determination of nucleosome enrichment factor, changes in caspase-3 activity, loss of mitochondrial membrane potential (MMP) and also the localization of phosphatidylserine in the plasma membrane. Changes in whole genome gene expression levels were examined by Illumina Human HT-12v4 beadchip microarrays. There were significant increases in caspase-3 activity, loss of MMP, and increases in apoptotic cell population in response to Quercitrin in A549 and NCI-H358 NSCLC cells in a time- and dose-dependent manner.
CONCLUSIONS:
Our results demonstrated that genes involved in leukocyte transendothelial migration, cell adhesion and phosphatidylinositol signaling system pathways were the most statistically significant pathways in NCI-H358 and A549 cells. These results revealed that Quercitrin has antiproliferative and apoptotic effects on lung cancer cells by modulating the immune response. After confirming its anticarcinogenic effects in vivo, Quercitrin could be a novel and strong anticancer agent against NSCLC.

Inhibition of major virulence pathways of Streptococcus mutans by quercitrin and deoxynojirimycin: a synergistic approach of infection control.[Pubmed: 24622055]

PLoS One. 2014 Mar 12;9(3):e91736.

To evaluate the synergistic effect of Quercitrin and Deoxynojirimycin (DNJ) together with their individual inhibitory effect against virulence pathways of Streptococcus mutans.
METHODS AND RESULTS:
MICs of both the compounds were determined by the microdilution method, followed by their in vitrosynergy using checkerboard and time kill assay. The nature of interaction was classified as synergistic on the basis of fractional inhibitory concentration index (FICI) value of ≤0.5. Furthermore, the activity of Quercitrin and DNJ was evaluated individually and in combination against various cariogenic properties of S. mutans UA159 such as acidogenesis, aciduracity, glucan production, hydrophobicity, biofilm and adherence. Moreover, expression of virulent genes in S. mutans was analysed by quantitative RT- PCR (qRT-PCR) and inhibition of F1F0-ATPase, lactate dehydrogenase and enolase was also evaluated. Finally, scanning electron microscopy (SEM) was used to investigate structural obliteration of biofilm. The in vitro synergism between Quercitrin and DNJ was observed, with a FICI of 0.313. Their MIC values were found to be 64 μg/ml and 16 μg/ml respectively. The synergistic combination consistently showed best activity against all the virulence factors as compared to Quercitrin and DNJ individually. A reduction in glucan synthesis and biofilm formation was observed at different phases of growth. The qRT-PCR revealed significant downregulation of various virulent genes. Electron micrographs depicted the obliteration of biofilm as compared to control and the activity of cariogenic enzymes was also inhibited.
CONCLUSIONS:
The whole study reflects a prospective role of Quercitrin and DNJ in combination as a potent anticariogenic agent against S. mutans.

In vivo quercitrin anti-inflammatory effect involves release of quercetin, which inhibits inflammation through down-regulation of the NF-kappaB pathway.[Pubmed: 15668926 ]

Eur J Immunol. 2005 Feb;35(2):584-92.

Quercetin is a common antioxidant flavonoid found in vegetables, which is usually present in glycosylated forms, such as Quercitrin (3-rhamnosylquercetin). Previous in vitro experiments have shown that quercetin exerts a bigger effect than Quercitrin in the down-regulation of the inflammatory response. However, such results have not been reproduced in in vivo experimental models of intestinal inflammation, in which quercetin did not show beneficial effects while its glycosides, Quercitrin or rutin, have demonstrated their effectiveness.
METHODS AND RESULTS:
In this study, we have reported that the in vivo effects of Quercitrin in the experimental model of rat colitis induced by dextran sulfate sodium can be mediated by the release of quercetin generated after glycoside's cleavage by the intestinal microbiota. This is supported by the fact that quercetin, but not Quercitrin, is able to down-regulate the inflammatory response of bone marrow-derived macrophages in vitro. Moreover, we have demonstrated that quercetin inhibits cytokine and inducible nitric oxide synthase expression through inhibition of the NF-kappaB pathway without modification of c-Jun N-terminal kinase activity (both in vitro and in vivo).
CONCLUSIONS:
As a conclusion, our report suggests that Quercitrin releases quercetin in order to perform its anti-inflammatory effect which is mediated through the inhibition of the NF-kappaB pathway.

Quercetin, but not rutin and quercitrin, prevention of H2O2-induced apoptosis via anti-oxidant activity and heme oxygenase 1 gene expression in macrophages.[Pubmed: 15876423]

Biochem Pharmacol. 2005 Jun 15;69(12):1839-51.

In the present study, we examine the protective mechanism of quercetin (QE) on oxidative stress-induced cytotoxic effect in RAW264.7 macrophages.
METHODS AND RESULTS:
Results of Western blotting show that QE but not its glycoside rutin (RUT) and quicitrin-induced HO-1 protein expression in a time- and dose-dependent manner, and HO-1 protein induced by QE was blocked by an addition of cycloheximide or actinomycin D. Induction of HO-1 gene expression by QE was accompanied by inducing ERKs, but not JNKs or p38, proteins phosphorylation. Addition of PD98059, but not SB203580 or SP600125, significantly attenuates QE-induced HO-1 protein and mRNA expression associated with blocking the expression of phosphorylated ERKs proteins. H(2)O(2) addition reduces the viability of cells by MTT assay, and appearance of DNA ladders, hypodiploid cells, and an increase in intracellular peroxide level was detected. Addition of QE, but not QI or RUT, significantly reduced the cytotoxic effect induced by H(2)O(2) associated with blocking the production of intracellular peroxide, DNA ladders, and hypodiploid cells. QE protection of cells from H(2)O(2)-induced apoptosis was significantly suppressed by adding HO inhibitor SnPP or ERKs inhibitor PD98059. Additionally, QE protects cells from H(2)O(2)-induced a decrease in the mitochondrial membrane potential and a release of cytochrome c from mitochondria to cytosol by DiOC6 and Western blotting assay, respectively. Activation of apoptotic proteins including the caspase 3, caspase 9, PARP, D4-GDI proteins was identified in H(2)O(2)-treated cells by Western blotting and enzyme activity assay, and that was significantly blocked by an addition of QE, but not RUT and QI. Furthermore, HO-1 catalytic metabolites carbon monoxide (CO), but not Fe(2+), Fe(3+), biliverdin or bilirubin, performed protective effect on cells from H(2)O(2)-induced cell death with an increase in HO-1 protein expression and ERKs protein phosphorylation.
CONCLUSIONS:
These data suggest that induction of HO-1 protein may participate in the protective mechanism of QE on oxidative stress (H(2)O(2))-induced apoptosis, and reduction of intracellular ROS production and mitochondria dysfunction with blocking apoptotic events were involved. Differential anti-apoptotic effect between QE and its glycosides RUT and QI via distinct HO-1 protein induction was also delineated.

Quercitrin and taxifolin stimulate osteoblast differentiation in MC3T3-E1 cells and inhibit osteoclastogenesis in RAW 264.7 cells.[Pubmed: 24060614]

Apoptotic Effects of Quercitrin on DLD-1 Colon Cancer Cell Line.[Pubmed: 25096395]

Pathol Oncol Res. 2015 Apr;21(2):333-8.

Quercetin, which is the most abundant bioflavonoid compound, is mainly present in the glycoside form of Quercitrin. Although different studies indicated that Quercitrin is a potent antioxidant, the action of this compound is not well understood. In this study, we investigated whether Quercitrin has apoptotic and antiproliferative effects in DLD-1 colon cancer cell lines.
METHODS AND RESULTS:
Time and dose dependent antiproliferative and apoptotic effects of Quercitrin were subsequently determined by WST-1 cell proliferation assay, lactate dehydrogenase (LDH) cytotoxicity assay, detection of nucleosome enrichment factor, changes in caspase-3 activity, loss of mitochondrial membrane potential (MMP) and also the localization of phosphatidylserine (PS) in the plasma membrane. There were significant increases in caspase-3 activity, loss of MMP, and increases in the apoptotic cell population in response to Quercitrin in DLD-1 colon cancer cells in a time- and dose-dependent manner.
CONCLUSIONS:
These results revealed that Quercitrin has antiproliferative and apoptotic effects on colon cancer cells. Quercitrin activity supported with in vivo analyses could be a biomarker candicate for early colorectal carcinoma.

Biochem Pharmacol. 2013 Nov 15;86(10):1476-86.

Flavonoids are natural antioxidants that positively influence bone metabolism. The present study screened among different flavonoids to identify biomolecules for potential use in bone regeneration. For this purpose, we used MC3T3-E1 and RAW264.7 cells to evaluate their effect on cell viability and cell differentiation.
METHODS AND RESULTS:
First, different doses of chrysin, diosmetin, galangin, Quercitrin and taxifolin were analyzed to determine the optimum concentration to induce osteoblast differentiation. After 48h of treatment, doses ≥100μM of diosmetin and galangin and also 500μM taxifolin revealed a toxic effect on cells. The same effect was observed in cells treated with doses ≥100μM of chrysin after 14 days of treatment. However, the safe doses of Quercitrin (200 and 500μM) and taxifolin (100 and 200μM) induced bone sialoprotein and osteocalcin mRNA expression. Also higher osteocalcin secreted levels were determined in 100μM taxifolin osteoblast treated samples when compared with the control ones. On the other hand, Quercitrin and taxifolin decreased Rankl gene expression in osteoblasts, suggesting an inhibition of osteoclast formation. Indeed, osteoclastogenesis suppression by Quercitrin and taxifolin treatment was observed in RAW264.7 cells.
CONCLUSIONS:
Based on these findings, the present study demonstrates that Quercitrin and taxifolin promote osteoblast differentiation in MC3T3-E1 cells and also inhibit osteoclastogenesis in RAW264.7 cells, showing a positive effect of these flavonoids on bone metabolism.