Enzymatic de-glycosylation of rutin improves its antioxidant and antiproliferative activities

Abstract

Bioavailability and biological properties of flavonoid glycosides can be improved after the enzymatic hydrolysis of specific glycosyl groups. In this study, we evaluate the antioxidant and antiproliferative potential of rutin after enzymatic hydrolysis performed by α-l-rhamnosidases (hesperidinase from Penicillium sp. and naringinase from Penicillium decumbens) previously heated at 70°C for 30 min to inactivate the undesirable β-d-glucosidase activity. The highest in vitro antioxidant activity determined by DPPH radical scavenging was achieved with rutin hydrolyzed by hesperidinase. Rutin was predominantly bioconverted into quercetin-3-glucoside. There was no statistical difference between xanthine oxidase inhibition by rutin before and after hydrolysis. However, in vitro inhibitory activity against ten human tumor cell lines showed that hydrolyzed rutin exerted a more potent antiproliferative effect than quercetin and rutin on various cancer cell lines, specially glioma, and ovarian and breast adenocarcinomas. These results indicate that quercetin-3-glucoside could be a promising functional derivative obtained by rutin hydrolysis.

Review of anticancer mechanisms of isoquercitin

“…In vitro studies comparing the antioxidant effect of flavonols (glycosides and aglycones) confirmed that their protective efficacy against lipid peroxidation reaction were mediated by free radicalscavenging activities [3,7] . However, it has been reported that these substances may also be cytotoxic and damage the cell membrane (mainly erythrocytes) in the presence of ROS, and thereby become extremely harmful to living organisms them selves [28] .…”

“…In vitro studies comparing the antioxidative effects of quercetin, IQ and other quercetin glycosides in liposomal phospholipid suspensions also demonstrated that the quercetin aglycone is a more efficient antioxidant than its glycoside [7,31,32] . This result should not reduce the credibility of IQ as an antioxidant compound since que rcetin (aglycone) is not the dominant form in nature and has an inferior bioavailability to Q3G [2,33] .…”

“…A fatenriched diet enhances quercetin3Oglucoside bioavailability, which might be owing to improved solubility and enhanced absorption of the lipophilic quercetin aglycone via lipid micelles, as well as delayed elimination of quercetin from the plasma owing to a prolonged enter ohepatic circulation [12] . It is important to note that follow ing the enzymatic hydrolysis by hesperidinase, rutin is mainly bioconverted into Q3G [4,7,8,1012] , thereby increasing the absorption [15] and bioavailability [16] .…”

“…IQ exerts antioxidative effects by inhibiting lipid peroxi dation via interference with enzyme activity (xanthine oxidase), chelation of redoxactive metals, increased absorption of vitamin C, and direct scavenging of ROS such as singlet oxygen, hydroxyl, peroxyl, peroxynitrite, and superoxide radicals [1,2,7,26,27] . In vitro studies comparing the antioxidant effect of flavonols (glycosides and aglycones) confirmed that their protective efficacy against lipid peroxidation reaction were mediated by free radicalscavenging activities [3,7] .…”

“…Enzymatically modified IQ is the product of this procedure and consists of a mixture that includes Q3G, Q4G, rutin, and other small metabolites [57] . Recent in vitro and in vivo studies with flavonols, particularly IQ, have demonstrated their potential activities including antioxidants, anti-inflammatory, antiallergic, and antiproliferative among other effects [2,7] . This review contributed to clarifying the absorption, bioavailability, and chemopreventive effects of IQ as well as its use in the treatment of cancer.…”