Quercetin inhibition

Xing, N, Y Chen, SH Mitchell, and CYF Young. 2001. Quercetin inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells. Carcinogenesis 22(3) 409 414. 

Figure 2. Representative polarographlc traces that depict effects of quercetin (Quer.) on oxygen utilization by mung bean mitochondria with malate as substrate. Trace A, stimulation of state 4 respiration by FCCP trace B, lack of state 4 stimulation by quercetin trace C, circumvention of ollgomycln (ollg.)-lnhlblted state 3 respiration by FCCP trace D, lack of circumvention of antlmycln A-Inhibited state 3 respiration by FCCP and trace E, lack of circumvention of quercetin-Inhibited state 3 respiration by FCCP. Rates of oxygen utilization, expressed as nmoles 02/mS protein min, are Indicated parenthetically.

As depleted in Scheme A, valinomycln forms a lipid-soluble complex with K an transports it across the membrane. An increase in internal K will be accompanied by the movement (diffusion) of the Cl counter ion, in some as yet unknown manner, to maintain electroneutrality. The increase in the matrix concentration of KCl will result in the osmotic Influx of water. Swelling is measured as a decrease in absorbance. The extent of swelling under control conditions is shown in the 0 trace. Quercetin inhibited, in a concentration-dependent manner, the extent of osmotic swelling. 

In isosmotlc solutions, movement of neutral amino acids such as prollne across the inner membrane into the matrix results in swelling of mitochondria (20). As shown in Figure 3C, the movement of proline is thought to occur via a uniport. The increased concentration of proline in the matrix produces an osmotic-induced swelling. Kinetics of the swelling response is shown in the 0 (control) trace. Again, quercetin inhibited this response in a concentration-dependent manner. 

Kobuchi, H., Roy, S., Sen, C.K., Nguyen, H.G., and Packer, L., Quercetin inhibits inducible ICAM-1 expression in human endothelial cells through the JNK pathway. Am. J. Physiol, 277, C403, 1999. 

Alcocer, F., Whitley, D., Salazar-Gonzalez, J.F., Jordan, W.D., Sellers, M.T., Eckhoff, D.E., Suzuki, K., MacRae, C., and Bland, K.L., Quercetin inhibits human vascular smooth muscle cell proliferation and migration. Surgery, 131, 198, 2002. 

Kang, Z.C., Tsai, S.J., and Lee, H., Quercetin inhibits benzo[a]pyrene-induced DNA adducts in human Hep G2 cells by altering cytochrome P-450 lAl expression, Nutr. Cancer, 35, 175, 1999. 

The degree of inhibition is dependent on the type of inducer and on the structure of the flavonoid. At 30 pM, fisetin, kaempferol or quercetin inhibit the platelet aggregation induced by arachidonic acid, whereas morin and myricetin are effective only at concentrations greater than 150 pM... 

Inflammation is now recognized as a key process in atherogenesis [Libby, 2002]. The potential for dietary flavonoids to inhibit inflammatory activities is of particular interest. A potential anti-inflammatory feature of the flavonoids is the ability to inhibit the biosynthesis of eicosanoids. Selected phenolic acids and some flavonoids have been shown to inhibit both cyclooxygenase (COX) and 5-lipoxygenase (5-LO) pathways [Nijveldt et al., 2001 Takano-Ishikawa et al., 2006], Epicatechin and related flavonoids have been shown to inhibit the synthesis of pro-inflammatory cytokines in vitro [Sanbongi et al., 1997], and plasma metabolites of catechin and quercetin inhibit the adhesion of monocytes to cultured endothelial cells [Koga and Meydani, 2001]. Silymarin has been shown to inhibit the production of inflammatory cytokines, such as interleukin-1, interferon-, and tumor necrosis factor-a (TNFa), from macrophages and T-cells [Matsuda et al., 2005], Some flavonoids can inhibit neutrophil... 

Romero M, Jimenez R, Sanchez M, Lopez-Sepulveda R, Zarzuelo MJ, O Valle F, Zarzuelo A, Perez-Vizcaino F, Duarte J. 2008. Quercetin inhibits vascular superoxide production induced by endothelin-1 Role of NADPH oxidase, uncoupled eNOS and PKC. Atherosclerosis. 

Quercetin inhibits topoisomerase II activity. Similar to genistein, it enhances topoisomerase-II-dependent DNA cleavage complexes. It also inhibits topoisomerase-II-catalyzed ATP hydrolysis. Because quercetin is an intercalative compound, it may enhance DNA cleavage by a mechanism similar to that of doxorubicin. Quercetin also inhibits several PTKs, with IC50 values that are comparable to or lower than those of genistein. 

Quercetin Inhibits cellular mutation, carcinogens, clot formation, and inflammation Grape skins, red and white wine... 

Sanderson, J., McLauchlan, W. R., and Williamson, G., Quercetin inhibits hydrogen peroxide-induced oxidation of die rat lens. Free Radic. Biol. Med. 26,639—645 (1999). 

In our experiments, kaempferol was ineffective in P-gp inhibition however, chrysin had a significant inhibitory effect. The rotenoid derivatives, amorphigenin and rotenone, had their MDR-modulating activity because of their structural difference of a hydroxyl (-OH) group at the position of C-8. The concentrations of flavonoids tested in this study had greater effects on the experimental results, then, a low concentration of quercetin activated the activity of P-gp, whereas a high concentration of quercetin inhibited the Pgp. A similar biphasic effect has been found for kaempferol. 

Blackburn, W.D. Heck, L.W. Wallace, R.W. The bioflavonoid quercetin inhibits neutrophil degranulation, superoxide production, and the phosphorylation of specific neutrophil proteins. Biochem. Biophys. Res. Commun. 1987, 144, 1229-1236. 

In a study on human promyelocytic leukaemia HL-60 cells, quercetin reduced cellular groAvth dose-dependently, and abolished it at a concentration of 80 pM. This effect was attributed to the concomitant inhibition of membrane, but not cytosolic, PTK activity, determined on poly Glu-Tyr (4 1) as a substrate (IC50 = 20.1 pM), Inversely, quercetin inhibited cytosolic, but not membrane, PKC activity. As a possible result of the inhibition of phosphatidyl-inositol kinases, the production of phosphoinositides in intact HL-60 cells was greatly diminished by quercetin [46]. 

A recent study carried out by Beil et al. (1995) [142] shows that flavone, flavanone and quercetin inhibited H. pylori growth in a concentration-dependent manner. The most potent compound was flavone, with an antibacterial activity similar to that reported by colloidal bismuth subcitrate. 

Sanderson J, McLauchlan WR, Williamson G. Quercetin inhibits hydrogen peroxideinduced oxidation of the rat lens. Free Radic Biol Med 1999 26 639-645. 

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