• BMB Reports
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• v.42 no.5
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• pp.265-270
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• 2009

Due to their multiple biological activities, flavonoids have gained attention as potentially useful therapeutics for a variety of diseases including cancer, cardiovascular diseases, and autoimmune diseases. In this study, we demonstrated that several flavonoids, including kaempferol, quercetin, fisetin, and chrysin block TNF-$\alpha$ induced IL-8 promoter activation and gene expression in HEK 293 cells. In addition, phosphorylation and degradation of $I{\kappa}B{\alpha}$ and translocation of NF-${\kappa}B$ p65 were inhibited by these flavonoids in TNF-$\alpha$-stimulated HEK 293 cells. Furthermore, generation of reactive oxygen species (ROS) in response to TNF-$\alpha$ was reduced by the flavonoids. Moreover, although pretreatment with fisetin, quercetin, or chrysin decreased cell viability, kaempferol did not. Taken together, these findings suggest that kaempferol would be useful for the treatment of TNF-$\alpha$-induced inflammatory diseases.

• Archives of Pharmacal Research
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• v.28 no.5
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• pp.573-581
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• 2005

Flavonoids, a group of low molecular weight phenylbenzopyrones, have various pharmacological properties including antioxidant activity, anticancer, and immunomodulatory effects. In the present study, lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate/phytohemagglutinin (PMA/PHA) were used as stimulants for RAW 264.7 macrophages and human peripheral blood mononuclear cell (hPBMC), and tumor necrosis factor (TNF)-${\alpha}$ and interleukin (IL)-2 productions were measured. In addition, flavonoids were examined for their effects on LPS-induced NO production in RAW 264.7 macrophages. The results showed that all compounds were not strongly cytotoxic at the tested concentrations on hPBMC and RAW 264.7 macrophages. On immunomodulatory properties, catechin, epigallocatechin (EGC), naringenin, and fisetin repressed NO production and TNF-${\alpha}$ secretion. Furthermore, catechin, epigallocatechin gallate (EGCG), epicatechin (EC), luteolin, chrysin, quercetin, and galangin increased IL-2 secretion while EGC, apigenin, and fisetin inhibited the secretion. These results indicated that flavonoids have the capacity to modulate the immune response and have a potential anti-inflammatory activity. There was no obvious structure-activity relationship regard to the chemical composition of the flavonoids and their cell biological effects.

• Journal of Pharmaceutical Investigation
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• v.34 no.2
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• pp.95-99
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• 2004

One mechanism which plays a prominent role in development of multi-drug resistance seen in cancer cells is the over-expression of P-glycoprotein (P-gp). It is known that compounds found in vegetables and fruits not only have anticarcinogenic properties but may also modulate P-gp activity. The effect of some dietary components on efflux of daunomycin (DNM), a P-gp substrate, was examined in P-gp over-expressed human uterine sarcoma cell line, MES-SA/DX5. The efflux of DNM from the cells was significantly inhibited by quercetin and verapamil, but not by 1-naphtyl-isothiocyanate (NITC). The $IC_{50}$ values for DNM in MES-SA/DX5 cells were increased by flavonoids (quercetin and fisetin), but not by NITC after 72 hour incubation with dietary constituents. In conclusion, flavonoids may play a role in the modulation of P­-gp activity in human uterine sarcoma cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.1
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• pp.97-103
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• 2015

This study investigated changes in phenolic contents of different parts of Rhus verniciflua Stokes (RV) according to extraction conditions. Bark and xylem parts of RV were extracted at 80, 100, 120, 140, and $160^{\circ}C$ for 1, 3, and 5 h, respectively. Major phenolic compounds (gallic acid, protocatechuic acid, fustin, fisetin, sulfuretin, and butein) of RV were analyzed. The gallic acid, fisetin, sulfuretin, and butein contents significantly increased as extraction temperature increased. Protocatechuic acid and fustin contents increased as increasing extraction temperature to $120^{\circ}C$ and decreased afterward. The gallic acid, protocatechuic acid, and butein contents of bark were higher than those of xylem extracts. The optimal extraction conditions of gallic acid, protocatechuic acid, fustin, fisetin, sulfuretin, and butein were $160^{\circ}C/3h$ (380.22 mg%), $120^{\circ}C/1h$ (9.25 mg%), $100^{\circ}C/3h$ (206.97 mg%), $140^{\circ}C/5h$ (93.84 mg%), $140^{\circ}C/5h$ (16.07 mg%) and $160^{\circ}C/5h$ (1.49 mg%), respectively. These results suggest that the optimum extraction temperature and time considering RV extraction yield and cost are $140^{\circ}C$ and 3 h, respectively.

• Applied Biological Chemistry
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• v.32 no.1
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• pp.37-43
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• 1989

Some phenolics were examined as an antioxidant for the autoxidation of soybean oil. Soybean oil was autoxidized under a mild condition (the flow rate of 67ml $O_{2}/min$ and $50^{\circ}C$). The antioxidant effect was estimated by active oxygen method. Phenolics show distinctive antioxidant effect, and the effect is prominent when cupper or iron was added. Phenolics showed a tendency to increase antioxidant effect with an increase of the number of hydroxyl group, and the increasing order was ferulic acid, quinalizarin, sesamol, alizarin, fisetin and purpurogallin. However, the effect was remarkably low in ferulic acid, alizarin and quinalizarin. It was found that the antioxidant effect was dependent on the functional group and geometric molecular structure of phenolics.

• Bulletin of the Korean Chemical Society
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• v.29 no.7
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• pp.1311-1314
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• 2008

Bacillus halodurans O-methyltransferase (BhOMT) is an S-adenosylmethionine dependent methyltransferase. In our previous study, three dimensional structure of the BhOMT has been determined by comparative homology modeling and automated docking study showed that two hydroxyl groups at 3'- and 4'-position in Bring and structural rigidity of C-ring resulting from the double bond characters between C2 and C3 of flavonoid, were key factors for interaction with BhOMT. In the present study, BhOMT was cloned and expressed. Binding assay was performed on purified BhOMT using fluorescence experiments and binding affinity of luteolin, quercetin, fisetin, and myricetin were measured in the range of $10^7$. Fluorescence quenching experiments indicated that divalent cation plays a critical role on the metal-mediated electrostatic interactions between flavonoid and substrate binding site of BhOMT. Fluorescence study confirmed successfully the data obtained from the docking study and these results imply that hydroxyl group at 7-position of luteolin, quercetin, fisetin, and myricetin forms a stable hydrogen bonding with K211 and carboxyl oxygen of C-ring forms a stable hydrogen bonding with R170. Hydroxyl group at 3'-and 4'-position in the B-ring also has strong $Ca^{2+}$ mediated electrostatic interactions with BhOMT.

• Archives of Pharmacal Research
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• v.28 no.7
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• pp.823-828
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• 2005

Multidrug resistance (MDR) is one of the most significant obstacles in cancer chemotherapy. One of the mechanisms involved in the development of MDR is the over-expression of P-glycoprotein (P-gp). It is widely known that natural compounds found in vegetables, fruits, plant-derived beverages and herbal dietary supplements not only have anticancer properties, but may also modulate P-gp activity. Therefore, the purpose of this investigation was to examine the effects of naturally occurring products on P-gp function in human breast cancer cell lines, MCF-7 (sensitive) and MCF-7/ADR (resistant). The accumulation of daunomycin (DNM), a P-gp substrate, was greater in the sensitive cells compared to the resistant cells, while the efflux of DNM was higher in the resistant cells compared to the sensitive cells over a period of 2h. The $IC_{50}$ value of DNM in the resistant cells was about 22 times higher than that in the sensitive cells, indicating an over-expression of P-gp in the resistant cells, MCF-7/ADR. All of the compounds tested, with the exception of fisetin, significantly decreased the $IC_{50}$ value of DNM. Biochanin A showed the greatest increase in $[^3H]-DNM$ accumulation, increasing by $454.3{\pm}19.5%$ in the resistant cells, whereas verapamil, the positive control, increased the accumulation by $229.4{\pm}17.6%$. Also, the accumulation of $[^3H]-DNM$ was increased substantially by quercetin and silymarin while it was reduced by fisetin. Moreover, biochanin A, silymarin, and naringenin significantly decreased DNM efflux from MCF-7/ADR cells compared with the control. These results suggest that some flavonoids such as biochanin A and silymarin may reverse MDR by inhibiting the P-gp function.

• Natural Product Sciences
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• v.10 no.2
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• pp.74-79
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• 2004

Dietary flavonoids are currently receiving considerable attention in developing novel cancer-preventive approaches because of their potential capacities to actively induce apoptosis of cancer cells. In our previous report, a flavonoid fraction, which consisted mainly of protocatechuic acid, fustin, fisetin, sulfuretin, and butein and named RCMF (RVS chloroform-methanol fraction), was prepared from a crude acetone extract of Rhus verniciflua Stokes (RVS) that is traditionally used as food additive and herbal medicine. In this study, we evaluated the effects of the RCMF on cell proliferation and apoptosis using SV40-transformed tumorigenic hepatocytes, BNL SV A.8. Tritium uptake assay showing the proliferative capacity of the cells was strongly suppressed in the presence of RCMF. This anti-proliferative effect was further confirmed through trypan blue exclusion. RCMF-mediated suppression of cell growth was verified to be apoptotic, based on the increase in DNA fragmentation, low fluorescence intensity in nuclei after propidium iodide staining, and the appearance of DNA laddering. Collectively, this study demonstrated that RCMF can be approached as a potential agent that is capable of significantly inhibiting cell growth of hepatic cancer cells.

• Archives of Pharmacal Research
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• v.21 no.4
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• pp.478-480
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• 1998

The structure activity relationship of flavonoids for anti-allergic actions was studied by determining the $IC_{50}$ values for the degranulation. The hexosaminidase release from RBL-2H3 cells (degranulation marker) was employed as an estimate for the anti-allergic actions. Among 22 flavonoid compounds tested, luteolin, apigenin, diosmetin, fisetin, and quercetin were found to be most active with $IC_{50}$ values less than 10 $\mu\textrm{M}$.

• Journal of Environmental Science International
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• v.26 no.3
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• pp.381-392
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• 2017

The present study aimed to investigate the effects of low temperature on the growth, yield, quality, and biologically active compounds of strawberry and obtain basic information for developing a technology for stable growth of strawberry in greenhouses. Growth of strawberry, including leaf number, area, and length, plant height, and dry weight was better at the optimum growth temperature of $20^{\circ}C$ than at a lower temperature of $15^{\circ}C$. At the low temperature of $15^{\circ}C$, the cultivar 'Maehyang' was more tolerant and displayed better growth rate than 'Seolhyang'. At $15^{\circ}C$, the fruit production per week and fruit weight was lower than that at $20^{\circ}C$. In contrast, fruit length and diameter were not significantly different between the two growth temperatures. Growth temperature also did not affect the fruit color index, Hunter L, a, b value, or fruit firmness. However, the sugar content of strawberries grown at $15^{\circ}C$ was higher by 0.8 and 1.5 Brix for 'Seolhyang' and 'Maehyang', respectively, than of those grown at $20^{\circ}C$. There was no difference in the content of fisetin, a biologically active compound, for 'Seolhyang' at both growth temperatures, however, the fisetin content of 'Maehyang' was higher at $20^{\circ}C$ than at $15^{\circ}C$. Cinchonine and ellagic acid content of 'Seolhyang' was higher at $20^{\circ}C$ than at $15^{\circ}C$, whereas that of 'Maehyang' was higher at $15^{\circ}C$ than at $20^{\circ}C$. Quercetin content showed no significant differences with respect to growth temperature, however, it tended to increase at $20^{\circ}C$. The cinnamic acid content of 'Seolhyang' was higher at $15^{\circ}C$ than at $20^{\circ}C$, whereas that of 'Maehyang' increased at $20^{\circ}C$. Collectively, the biologically active compounds of strawberry were affected by growth temperature. Moreover, the content of these compounds tended to increase at $20^{\circ}C$, the optimum growth temperature, rather than at the sub-optimal growth temperature of $15^{\circ}C$.