Quercetin inhibitory activity

The ability of flavonoids (quercetin and rutin) to react with superoxide has been shown in both aqueous and aprotic media [59,94]. Then, the inhibitory activity of flavonoids in various enzymatic and nonenzymatic superoxide-producing systems has been studied. It was found that flavonoids may inhibit superoxide production by xanthine oxidase by both the scavenging of superoxide and the inhibition of enzyme activity, with the ratio of these two mechanisms depending on the structures of flavonoids (Table 29.4). As seen from Table 29.4, the data obtained by different authors may significantly differ. For example, in recent work [107] it was found that rutin was ineffective in the inhibition of xanthine oxidase that contradicts the previous results [108,109], The origins of such big differences are unknown. 

Whatever the mechanism of action for the inhibition of 5-lipoxygenase by flavonoids, it appears to be distinct from the antioxidant properties of these compounds. The results comparing antioxidant activity with leukotriene inhibitory activity clearly demonstrate this distinction. The profound effects of metabolic transformation on the anti-inflammation activity of dietary flavonoids such as quercetin must also be considered in relation to in vitro studies, and further highlights the need to use actual metabolic forms of flavonoids rather than the free aglycone or glycosides occurring in the diet. 

Loke WM, Proudfoot JM, Stewart S, McKinley AJ, Needs PW, Kroon PA, Hodgson JM, Croft KD. 2008c. Metabolic transformation has a profound effect on antiinflammatory activity of flavonoids such as quercetin Lack of association between antioxidant and lipoxygenase inhibitory activity. Biochem Pharmacol 75 1045-1053. 

As shown in Table 1, none of the compounds had the ability to inhibit HSV, while only quercetin-3,7-O-a-L-dirhamnoside had inhibitory activity against PI-3 in the range 8-32 pg/mL of maximum and minimum cytopathogenic effect (CPE) inhibitory concentrations, respectively. The inhibitory concentration range of this compound is on a vast scale, which resembles that of oseltamivir (32 to < 0.25 pg/mL). Besides, its maximum non-toxic concentration (MNTC) (64 pg/mL) was observed to be better than oseltamivir (32 pg/mL). 

On the other hand, flavonoids without side chains such as quercetin (43), naringenin (69), hesperetin (70), and kaempferol (106) did not inhibit the enzyme activity at a final concentration of 800 xM. These results suggest that the lavandulyl side chain and the position of the hydroxy group might be important for the high DGAT inhibitory activity. Kurarinone (13) also inhibited de novo synthesis of triacylglycerol (TG) in Raji cells (Fig. 31) [22,33]. 

Inhibitory activity against a-amylase by flavonoids and anthocyanins has been reported (39). Herbs used in Nigerian traditional medicine for the treatment of diabetes mellitus are known to contain phenol compounds especially the flavonoid quercetin and the mechanism of their antidiadetic activity may be brought about by their amylase inhibiting activity and the antioxidant activity of the phenolic compounds. 

Tetramethyleneglutaric acid (TMG) (62) and alrestatin (AY-22,284) (63)) are known aldose reductase inhibitors. From natural products, a number of flavonoids have been reported to have aldose reductase inhibitory activity. Quercetin (64 1, R = H), quercitrin (64 2, R = L-rhamnose), rutin (64 3, R = rutinose (6-O-a -L-rhamnosyl-D-glucose)) and myricitrin (65 2, R = L-rhamnose) were much more effective inhibitors of aldose reductase from rat lens than TMG (62) and alrestatin (63) [66]. Quercetin with 3, 4 -dihydroxy substitution in ring C was more potent... 

The novel abietane-type diterpenes, danshenol A (92 1) and B (92 2), along with four known ones, dihydrotanshinone I (92 3), cryptotanshinone (92 4), tanshinone 1(92 5) and tanshinone IIA (92 6) were isolated from the roots of Salvia miltiorrhiza (Labiatae) [85]. Inhibitory activity was found in these six abietane-type diterpenes with activity more or less equal to quercetin. Danshenol A was the most potent, which was 56 times more than quercetin. 

Shen, S.C. et al.. In vitro and in vivo inhibitory activities of rutin, wogonin, and quercetin on lipopolysaccharide-induced nitric oxide and prostaglandin E2 production, Eur. J. Pharmacol,... 

These a-glucosidase inhibitory activities of 2, 2,5-trimethoxy-6,7-methylenedioxyisoflavanone (12) and tlatlancuayin (2 ,5-dimethoxy-6,7-methylenedioxyisoflavone, 11) were lower when compared to that (a-glucosidase inhibitory activities) of hyperoside (quercetin-3-O-galactoside, hyperin, 13) [34, 35],... 

Effects of Allelochemlcals on ATPases. Several flavonoid compounds inhibit ATPase activity that is associated with mineral absorption. Phloretin and quercetin (100 pM) inhibited the plasma membrane ATPase Isolated from oat roots (33). The naphthoquinone juglone was inhibitory also. However, neither ferulic acid nor salicylic acid inhibited the ATPase. Additional research has shown that even at 10 mM salicylic acid inhibits ATPase activity only 10-15% (49). This lack of activity by salicylic acid was substantiated with the plasma membrane ATPase Isolated from Neurospora crassa (50) however, the flavonols fisetln, morin, myricetin, quercetin, and rutin were inhibitory to the Neurospora ATPase. Flavonoids inhibited the transport ATPases of several animal systems also (51-53). Thus, it appears that flavonoids but not phenolic acids might affect mineral transport by inhibiting ATPase enzymes. 

Hamalainen M, Nieminen R, Vuorela P, Heinonen M and Moilanen E. 2007. Anti-inflammatory effects of flavonoids genistein, kaempferol, quercetin and daidzein inhibit STAT-1 and NF-kB activations whereas flavones, isorhamnetin, naringenins, and pelargonidin inhibit only NF-kB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophagues. Mediators Inflamm 2007 45673. 

The above findings are supported in the other studies of the inhibitory effects of flavonoids on iron-stimulated lipid peroxidation. Quercetin was found to be an inhibitor of iron-stimulated hepatic microsomal lipid peroxidation (/50 = 200 pmol I ) [134]. Flavonoids eriodictyol, luteolin, quercetin, and taxifolin inhibited ascorbate and ferrous ion-stimulated MDA formation and oxidative stress (measured by fluorescence of 2,7,-dichlorodihydro-fluorescein) in cultured retinal cells [135]. It should be mentioned that in recent work Heijnen et al. [136] revised the structure activity relationship for the protective effects of flavonoids against lipid peroxidation. 

It must be noted that the inhibitory effects of flavonoids and other antioxidants in nonhomogenous biological systems can depend not only on their reactivities in reactions with free radicals (the chain-breaking activities) but also on the interaction with biomembranes. Thus, Saija et al. [137] compared the antioxidant effects and the interaction with biomembranes of four flavonoids quercetin, hesperetin, naringen, and rutin in iron-induced... 

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