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Fu-an Wu - One of the best experts on this subject based on the ideXlab platform.
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Isoquercitrin production from rutin catalyzed by naringinase under ultrasound irradiation
Journal of Molecular Catalysis B-enzymatic, 2016Co-Authors: An Gong, D’assise Kinfack Tsabing, Fu-an Wu, Yan Xu, Jun WangAbstract:Abstract Isoquercitrin, a rare flavonol glycoside with wide biological activities and key synthetic intermediate for the production of enzymatically modified Isoquercitrin (EMIQ), was conducted by naringinase-catalyzed conversion of rutin under ultrasound irradiation. The maximum yields were obtained to 98.35 ± 3.13% and 95.20 ± 2.52% under conventional heating and ultrasound irradiation, respectively. The optimal results under ultrasound irradiation were obtained under the following conditions: rutin concentration 0.8 g/L, naringinase concentration 3000 U/L, reaction temperature 40 °C for 20 min, which was more economical than that with conventional heating. The reaction time was reduced from 60 min to 20 min, and the apparent kinetic parameter (Vm/Km) was increased 3.72-fold. The lower activity energy Ea under ultrasonic irradiation was 0.7-fold of that in an incubator reactor, which could easily initiate the enzymatic reaction. The association saturation constant Ka was 1.98-fold higher than that with conventional heating, showed a better affinity between rutin and naringinase detected by surface plasmon resonance (SPR) analysis. These results suggest that ultrasound irradiation can accelerate the enzymatic synthesis of Isoquercitrin from rutin.
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enhanced biocatalysis mechanism under microwave irradiation in Isoquercitrin production revealed by circular dichroism and surface plasmon resonance spectroscopy
Bioresource Technology, 2016Co-Authors: An Gong, Fu-an Wu, Xiaohui Xu, Jun WangAbstract:An efficient and rapid process for Isoquercitrin production by hesperidinase-catalyzed hydrolysis of rutin was successfully developed under microwave irradiation detecting the affinity by circular dichroism (CD) and surface plasmon resonance (SPR) spectroscopy. A maximum Isoquercitrin yield of 91.5±2.7% was obtained in 10min with the conditions of 10g/L hesperidinase, 2g/L rutin, 30°C and microwave power density 88.9W/L. Enzymatic reaction rate and Vm/Km in the microwave reactor were 6.34-fold higher than in a continuous flow microreactor and 1.24-fold higher than in a biphasic system. CD and SPR analysis results also showed that hesperidinase has a better selectivity and affinity (3.3-fold than in a batch reactor) to generate Isoquercitrin under microwave irradiation. Microwave irradiation greatly improved the reaction efficiency and productivity, leading to a more positive economical assessment. The binding affinity indicates the presence of strong multivalent interactions between rutin and hesperidinase under microwave irradiation.
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an effective biphase system accelerates hesperidinase catalyzed conversion of rutin to Isoquercitrin
Scientific Reports, 2015Co-Authors: Jun Wang, An Gong, Xiangyang Wu, Caifeng Yang, Fu-an WuAbstract:An effective biphase system accelerates hesperidinase-catalyzed conversion of rutin to Isoquercitrin
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enhancement of the selective enzymatic biotransformation of rutin to Isoquercitrin using an ionic liquid as a co solvent
Bioresource Technology, 2013Co-Authors: Jun Wang, Liang Yu, Fu-an WuAbstract:An ionic liquid (IL)-containing buffer system was first applied in the conversion of rutin to Isoquercitrin. High substrate solubility was achieved to enhance the selectivity and efficiency of hesperidinase-catalyzed reaction. Ten ILs were selected as co-solvents to assist catalytic reactions in this biotransformation process. The transformed products of rutin were identified by LC–MS. The [Bmim][BF4]-glycine-sodium hydroxide buffer (pH 9) (10:90, v/v) was found to be the best medium for the biotransformation of Isoquercitrin from rutin with higher selectivity and efficiency. The reaction time was reduced by 0.33-fold while the conversion of rutin and the yield of Isoquercitrin were increased by 1.67-fold and 2.33-fold. The results suggest that IL co-solvents have great potential to enhance the selectively enzymatic hydrolysis of rutin for Isoquercitrin production.
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selective hydrolysis by commercially available hesperidinase for Isoquercitrin production
Journal of Molecular Catalysis B-enzymatic, 2012Co-Authors: Jun Wang, Xiangyang Wu, Liang Yu, Fu-an WuAbstract:Abstract Isoquercitrin is a rare flavonol glycoside with various biological activities, and it is a primary synthetic precursor for enzymatically modified Isoquercitrin (EMIQ), which was recently approved as a multiple food additive. The enzymatic method has a great potential to produce Isoquercitrin from hydrolysis of rutin via selectively removing a terminal rhamnose. Commercially available hesperidinase was investigated and found that α - l -rhamnosidase achieves good catalytic capacity while β - d -glucosidase loses its activity at pH 7.0. The increased conversion of rutin to Isoquercitrin was found by the addition of some metal ions (K + , Li + , Mg 2+ , Zn 2+ and Al 3+ ). Electrospray ionization mass spectrometry (ESI-MS) and nuclear magnetic resonance (NMR) were used to identify Isoquercitrin from the transformed products. The enzymatic reaction conditions (temperature, substrate concentration, and reaction time) of Isoquercitrin from rutin were optimized, and the apparent kinetic parameters V m / K m at different temperatures were also measured. The results suggest that the commercially available hesperidinase can be applied into Isoquercitrin production via highly selective hydrolysis.
Jun Wang - One of the best experts on this subject based on the ideXlab platform.
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Isoquercitrin production from rutin catalyzed by naringinase under ultrasound irradiation
Journal of Molecular Catalysis B-enzymatic, 2016Co-Authors: An Gong, D’assise Kinfack Tsabing, Fu-an Wu, Yan Xu, Jun WangAbstract:Abstract Isoquercitrin, a rare flavonol glycoside with wide biological activities and key synthetic intermediate for the production of enzymatically modified Isoquercitrin (EMIQ), was conducted by naringinase-catalyzed conversion of rutin under ultrasound irradiation. The maximum yields were obtained to 98.35 ± 3.13% and 95.20 ± 2.52% under conventional heating and ultrasound irradiation, respectively. The optimal results under ultrasound irradiation were obtained under the following conditions: rutin concentration 0.8 g/L, naringinase concentration 3000 U/L, reaction temperature 40 °C for 20 min, which was more economical than that with conventional heating. The reaction time was reduced from 60 min to 20 min, and the apparent kinetic parameter (Vm/Km) was increased 3.72-fold. The lower activity energy Ea under ultrasonic irradiation was 0.7-fold of that in an incubator reactor, which could easily initiate the enzymatic reaction. The association saturation constant Ka was 1.98-fold higher than that with conventional heating, showed a better affinity between rutin and naringinase detected by surface plasmon resonance (SPR) analysis. These results suggest that ultrasound irradiation can accelerate the enzymatic synthesis of Isoquercitrin from rutin.
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enhanced biocatalysis mechanism under microwave irradiation in Isoquercitrin production revealed by circular dichroism and surface plasmon resonance spectroscopy
Bioresource Technology, 2016Co-Authors: An Gong, Fu-an Wu, Xiaohui Xu, Jun WangAbstract:An efficient and rapid process for Isoquercitrin production by hesperidinase-catalyzed hydrolysis of rutin was successfully developed under microwave irradiation detecting the affinity by circular dichroism (CD) and surface plasmon resonance (SPR) spectroscopy. A maximum Isoquercitrin yield of 91.5±2.7% was obtained in 10min with the conditions of 10g/L hesperidinase, 2g/L rutin, 30°C and microwave power density 88.9W/L. Enzymatic reaction rate and Vm/Km in the microwave reactor were 6.34-fold higher than in a continuous flow microreactor and 1.24-fold higher than in a biphasic system. CD and SPR analysis results also showed that hesperidinase has a better selectivity and affinity (3.3-fold than in a batch reactor) to generate Isoquercitrin under microwave irradiation. Microwave irradiation greatly improved the reaction efficiency and productivity, leading to a more positive economical assessment. The binding affinity indicates the presence of strong multivalent interactions between rutin and hesperidinase under microwave irradiation.
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an effective biphase system accelerates hesperidinase catalyzed conversion of rutin to Isoquercitrin
Scientific Reports, 2015Co-Authors: Jun Wang, An Gong, Xiangyang Wu, Caifeng Yang, Fu-an WuAbstract:An effective biphase system accelerates hesperidinase-catalyzed conversion of rutin to Isoquercitrin
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Microwave Assisted Synthesis of Isoquercitrin Using Enzymatic Hydrolysis of Rutin
Advanced Materials Research, 2014Co-Authors: Jun Wang, An Gong, Xiangyang WuAbstract:A novel and rapid synthesis of Isoquercitrin using enzymatic hydrolysis of rutin under microwave irradiation was investigated. In the [Bmim][BF4]-buffer (pH 9.0) system under microwave irradiation, rutin conversion, Isoquercitrin yield and quercetin yield were 89.18%, 84.74% and 2.79%, respectively, in conditions of 5 min and 30 °C. The preparation cost of Isoquercitrin was significantly reduced by decreasing reaction time (from 10 h to 5 min) and increasing reaction efficiency (by 120 times).
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ultrafast synthesis of Isoquercitrin by enzymatic hydrolysis of rutin in a continuous flow microreactor
Journal of The Serbian Chemical Society, 2014Co-Authors: Jun Wang, An Gong, Shuangshuang Gu, Xiangyang WuAbstract:Isoquercitrin is a rare flavonol glycoside with a wide range of biological activities and is a key synthetic intermediate for the production of enzymatically modified Isoquercitrin. In order to establish an ultrafast biopro-cess for obtaining Isoquercitrin, a novel continuous flow biosynthesis of Isoquercitrin using the hesperidinase-catalyzed hydrolysis of rutin in a glass–polydimethylsiloxane (PDMS) microreactor was first performed. Using the developed microchannel reactor (200 μm width, 50 μm depth and 2 m length) with one T-shaped inlet and one outlet, the maximum yield of Isoquercitrin (98.6 %) was achieved in a short time (40 min) under the following optimum conditions: rutin concentration at 1 g L -1 , hesperidinase concentration at 0.1 g mL -1 , reaction temperature 40 °C, and a flow rate of 2 μL min -1 . The value of the activation energy, E a , of the enzymatic reaction was 4.61 kJ mol -1 , and the reaction rate and volumetric productivity were approximately 16.1-fold and 30 % higher, respectively, than those in a batch reactor were. Thus, the use of a continuous-flow microreactor for the enzymatic hydrolysis of rutin is an efficient and simple approach to achieve a relatively high yield of Isoquercitrin.
Jose G Abreu - One of the best experts on this subject based on the ideXlab platform.
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Isoquercitrin suppresses colon cancer cell growth in vitro by targeting the wnt β catenin signaling pathway
Journal of Biological Chemistry, 2014Co-Authors: Nathalia G Amado, Debora M Cerqueira, Danilo Predes, Barbara F Fonseca, Alice H Reis, Ana C Dudenhoeffer, Helena L Borges, Fabio A Mendes, Jose G AbreuAbstract:Abstract Flavonoids are plant-derived polyphenolic molecules that have potential biological effects including anti-oxidative, anti-inflammatory, anti-viral, and anti-tumoral effects. These effects are related to the ability of flavonoids to modulate signaling pathways, such as the canonical Wnt signaling pathway. This pathway controls many aspects of embryonic development and tissue maintenance and has been found to be deregulated in a range of human cancers. We performed several in vivo assays in Xenopus embryos, a functional model of canonical Wnt signaling studies, and also used in vitro models, to investigate whether Isoquercitrin affects Wnt/β-catenin signaling. Our data provide strong support for an inhibitory effect of Isoquercitrin on Wnt/β-catenin, where the flavonoid acts downstream of β-catenin translocation to the nuclei. Isoquercitrin affects Xenopus axis establishment, reverses double axes and the LiCl hyperdorsalization phenotype, and reduces Xnr3 expression. In addition, this flavonoid shows anti-tumoral effects on colon cancer cells (SW480, DLD-1, and HCT116), whereas exerting no significant effect on non-tumor colon cell (IEC-18), suggesting a specific effect in tumor cells in vitro. Taken together, our data indicate that Isoquercitrin is an inhibitor of Wnt/β-catenin and should be further investigated as a potential novel anti-tumoral agent.
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Isoquercitrin Suppresses Colon Cancer Cell Growth in Vitro by Targeting the Wnt/β-Catenin Signaling Pathway
Journal of Biological Chemistry, 2014Co-Authors: Nathalia G Amado, Debora M Cerqueira, Danilo Predes, Barbara F Fonseca, Alice H Reis, Ana C Dudenhoeffer, Helena L Borges, Fabio A Mendes, Jose G AbreuAbstract:Abstract Flavonoids are plant-derived polyphenolic molecules that have potential biological effects including anti-oxidative, anti-inflammatory, anti-viral, and anti-tumoral effects. These effects are related to the ability of flavonoids to modulate signaling pathways, such as the canonical Wnt signaling pathway. This pathway controls many aspects of embryonic development and tissue maintenance and has been found to be deregulated in a range of human cancers. We performed several in vivo assays in Xenopus embryos, a functional model of canonical Wnt signaling studies, and also used in vitro models, to investigate whether Isoquercitrin affects Wnt/β-catenin signaling. Our data provide strong support for an inhibitory effect of Isoquercitrin on Wnt/β-catenin, where the flavonoid acts downstream of β-catenin translocation to the nuclei. Isoquercitrin affects Xenopus axis establishment, reverses double axes and the LiCl hyperdorsalization phenotype, and reduces Xnr3 expression. In addition, this flavonoid shows anti-tumoral effects on colon cancer cells (SW480, DLD-1, and HCT116), whereas exerting no significant effect on non-tumor colon cell (IEC-18), suggesting a specific effect in tumor cells in vitro. Taken together, our data indicate that Isoquercitrin is an inhibitor of Wnt/β-catenin and should be further investigated as a potential novel anti-tumoral agent.
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Isoquercitrin isolated from hyptis fasciculata reduces glioblastoma cell proliferation and changes β catenin cellular localization
Anti-Cancer Drugs, 2009Co-Authors: Nathalia G Amado, Debora M Cerqueira, Fabio De Sousa Menezes, J F M Silva, Vivaldo Moura Neto, Jose G AbreuAbstract:Isoquercitrin isolated from the aerial parts of Hyptis fasciculata was evaluated according to its capacity to interfere with glioblastoma (Gbm) cell growth. Gbm cells were incubated with Isoquercitrin, quercetin, or rutin at concentrations of 25, 50, and 100 μmol/l for 24, 48, and 72 h. Quercetin an
Jiři Vrba - One of the best experts on this subject based on the ideXlab platform.
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protective effect of Isoquercitrin against acute dextran sulfate sodium induced rat colitis depends on the severity of tissue damage
Pharmacological Reports, 2016Co-Authors: Norbert Cibicek, Jiři Vrba, Lenka Roubalova, Martina Zatloukalova, Jiři Ehrmann, Jana Zapletalova, Rostislav Veceřa, Jitka UlrichovaAbstract:Abstract Background Isoquercitrin (quercetin-3- O -β- d -glucopyranoside) is a flavonoid that exhibited antioxidant and anti-inflammatory activities in a number of in vitro and in vivo studies. Experimental evidence from rodent models of inflammatory bowel disease is, however, lacking. This study was designed to examine whether Isoquercitrin effectively and dose-dependently attenuates acute dextran sulfate sodium (DSS)-induced rat colitis. Methods Wistar rats were divided into negative control group (exposed to vehicle only), positive control group (DSS-induced colitis plus vehicle), low Isoquercitrin group (DSS pretreated with Isoquercitrin 1 mg/kg/day) and high Isoquercitrin group (DSS with Isoquercitrin 10 mg/kg/day). Isoquercitrin was administered daily for 14 days, and during the last 7 days rats drank DSS solution. The effect of Isoquercitrin on DSS-induced colitis was assessed clinically (e.g. disease activity index), biochemically (tissue myeloperoxidase activity, local cyclooxygenase-2 expression), using histology (standard hematoxylin-eosin-based histomorphometry, immunohistochemical detection of inducible nitric oxide synthase) and hematology (blood count). Results Isoquercitrin dose-dependently ameliorated whole colon shortening and mitigated DSS-induced expression of cyclooxygenase-2 and inducible nitric oxide synthase in the descending segment of the organ. However, when different parts of colon were assessed histomorphometrically, the results did not globally support the protective role of this flavonoid. Tissue healing trends observable in the descending colon were not apparent in the rectum, where histological damage was most severe. Conclusions We surmise that Isoquercitrin may be effective in the prevention of acute colitis. Besides being dose-dependent, the potency of orally administered Isoquercitrin may depend on the severity of tissue damage and/or on the site of its action.
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sulfation modulates the cell uptake antiradical activity and biological effects of flavonoids in vitro an examination of quercetin Isoquercitrin and taxifolin
Bioorganic & Medicinal Chemistry, 2015Co-Authors: Lenka Roubalova, Jitka Ulrichova, Kateřina Purchartova, Barbora Papouskova, Jan Vacek, Jiři VrbaAbstract:Abstract Quercetin 3′- O -sulfate is one of the main metabolites of the natural flavonoid quercetin in humans. This study was designed to prepare quercetin 3′- O -sulfate ( 1 ), Isoquercitrin 4′- O -sulfate ( 2 ) and taxifolin 4′- O -sulfate ( 3 ) by the sulfation of quercetin, Isoquercitrin (quercetin 3- O -glucoside) and taxifolin (2,3-dihydroquercetin) using the arylsulfate sulfotransferase from Desulfitobacterium hafniense , and to examine the effect of sulfation on selected biological properties of the flavonoids tested. We found that flavonoid sulfates 1 – 3 were weaker DPPH radical scavengers than the corresponding nonsulfated flavonoids, and that 1 – 3 , unlike quercetin, did not induce the expression of either heme oxygenase-1 in RAW264.7 cells or cytochrome P450 1A1 in HepG2 cells. In both cell types, the cell uptake of compounds 1 – 3 was much lower than that of quercetin, but comparable to that of the glycoside Isoquercitrin. Moreover, HPLC/MS metabolic profiling in HepG2 cells showed that flavonoid sulfates 1 – 3 were metabolized to a limited extent compared to the nonsulfated compounds. We conclude that sulfation of the tested flavonoids reduces their antiradical activity, and affects their cell uptake and biological activity in vitro.
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Isoquercitrin pharmacology toxicology and metabolism
Food and Chemical Toxicology, 2014Co-Authors: Kateřina Valentova, Jiři Vrba, Martina Banciřova, Jitka UlrichovaAbstract:Abstract The flavonoid Isoquercitrin (quercetin-3- O -β- d -glucopyranoside) is commonly found in medicinal herbs, fruits, vegetables and plant-derived foods and beverages. This article reviews the occurrence, preparation, bioavailability, pharmacokinetics, toxicology and biological activity of Isoquercitrin and “enzymatically modified (α-glucosylated) Isoquercitrin” (EMIQ). Pure Isoquercitrin can now be obtained on a large scale by enzymatic rutin hydrolysis with α- l -rhamnosidase. Isoquercitrin has higher bioavailability than quercetin and displays a number of chemoprotective effects both in vitro and in vivo , against oxidative stress, cancer, cardiovascular disorders, diabetes and allergic reactions. Although small amounts of intact Isoquercitrin can be found in plasma and tissues after oral application, it is extensively metabolized in the intestine and the liver. Biotransformation of Isoquercitrin includes deglycosylation, followed by formation of conjugated and methylated derivatives of quercetin or degradation to phenolic acids and carbon dioxide. The acceptable daily intake of (95%) Isoquercitrin and of EMIQ was estimated to be 5.4 and 4.9 mg/kg/day, respectively. Adverse effects of higher doses in rats included mostly (benign) chromaturia; nevertheless some drug interactions may occur due to the modulation of the activity and/or expression of drug metabolizing/transporting systems. With respect to the safety, affordability and beneficial pharmacological activities, highly pure Isoquercitrin is a prospective substance for food supplementation.
Jitka Ulrichova - One of the best experts on this subject based on the ideXlab platform.
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protective effect of Isoquercitrin against acute dextran sulfate sodium induced rat colitis depends on the severity of tissue damage
Pharmacological Reports, 2016Co-Authors: Norbert Cibicek, Jiři Vrba, Lenka Roubalova, Martina Zatloukalova, Jiři Ehrmann, Jana Zapletalova, Rostislav Veceřa, Jitka UlrichovaAbstract:Abstract Background Isoquercitrin (quercetin-3- O -β- d -glucopyranoside) is a flavonoid that exhibited antioxidant and anti-inflammatory activities in a number of in vitro and in vivo studies. Experimental evidence from rodent models of inflammatory bowel disease is, however, lacking. This study was designed to examine whether Isoquercitrin effectively and dose-dependently attenuates acute dextran sulfate sodium (DSS)-induced rat colitis. Methods Wistar rats were divided into negative control group (exposed to vehicle only), positive control group (DSS-induced colitis plus vehicle), low Isoquercitrin group (DSS pretreated with Isoquercitrin 1 mg/kg/day) and high Isoquercitrin group (DSS with Isoquercitrin 10 mg/kg/day). Isoquercitrin was administered daily for 14 days, and during the last 7 days rats drank DSS solution. The effect of Isoquercitrin on DSS-induced colitis was assessed clinically (e.g. disease activity index), biochemically (tissue myeloperoxidase activity, local cyclooxygenase-2 expression), using histology (standard hematoxylin-eosin-based histomorphometry, immunohistochemical detection of inducible nitric oxide synthase) and hematology (blood count). Results Isoquercitrin dose-dependently ameliorated whole colon shortening and mitigated DSS-induced expression of cyclooxygenase-2 and inducible nitric oxide synthase in the descending segment of the organ. However, when different parts of colon were assessed histomorphometrically, the results did not globally support the protective role of this flavonoid. Tissue healing trends observable in the descending colon were not apparent in the rectum, where histological damage was most severe. Conclusions We surmise that Isoquercitrin may be effective in the prevention of acute colitis. Besides being dose-dependent, the potency of orally administered Isoquercitrin may depend on the severity of tissue damage and/or on the site of its action.
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sulfation modulates the cell uptake antiradical activity and biological effects of flavonoids in vitro an examination of quercetin Isoquercitrin and taxifolin
Bioorganic & Medicinal Chemistry, 2015Co-Authors: Lenka Roubalova, Jitka Ulrichova, Kateřina Purchartova, Barbora Papouskova, Jan Vacek, Jiři VrbaAbstract:Abstract Quercetin 3′- O -sulfate is one of the main metabolites of the natural flavonoid quercetin in humans. This study was designed to prepare quercetin 3′- O -sulfate ( 1 ), Isoquercitrin 4′- O -sulfate ( 2 ) and taxifolin 4′- O -sulfate ( 3 ) by the sulfation of quercetin, Isoquercitrin (quercetin 3- O -glucoside) and taxifolin (2,3-dihydroquercetin) using the arylsulfate sulfotransferase from Desulfitobacterium hafniense , and to examine the effect of sulfation on selected biological properties of the flavonoids tested. We found that flavonoid sulfates 1 – 3 were weaker DPPH radical scavengers than the corresponding nonsulfated flavonoids, and that 1 – 3 , unlike quercetin, did not induce the expression of either heme oxygenase-1 in RAW264.7 cells or cytochrome P450 1A1 in HepG2 cells. In both cell types, the cell uptake of compounds 1 – 3 was much lower than that of quercetin, but comparable to that of the glycoside Isoquercitrin. Moreover, HPLC/MS metabolic profiling in HepG2 cells showed that flavonoid sulfates 1 – 3 were metabolized to a limited extent compared to the nonsulfated compounds. We conclude that sulfation of the tested flavonoids reduces their antiradical activity, and affects their cell uptake and biological activity in vitro.
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Isoquercitrin pharmacology toxicology and metabolism
Food and Chemical Toxicology, 2014Co-Authors: Kateřina Valentova, Jiři Vrba, Martina Banciřova, Jitka UlrichovaAbstract:Abstract The flavonoid Isoquercitrin (quercetin-3- O -β- d -glucopyranoside) is commonly found in medicinal herbs, fruits, vegetables and plant-derived foods and beverages. This article reviews the occurrence, preparation, bioavailability, pharmacokinetics, toxicology and biological activity of Isoquercitrin and “enzymatically modified (α-glucosylated) Isoquercitrin” (EMIQ). Pure Isoquercitrin can now be obtained on a large scale by enzymatic rutin hydrolysis with α- l -rhamnosidase. Isoquercitrin has higher bioavailability than quercetin and displays a number of chemoprotective effects both in vitro and in vivo , against oxidative stress, cancer, cardiovascular disorders, diabetes and allergic reactions. Although small amounts of intact Isoquercitrin can be found in plasma and tissues after oral application, it is extensively metabolized in the intestine and the liver. Biotransformation of Isoquercitrin includes deglycosylation, followed by formation of conjugated and methylated derivatives of quercetin or degradation to phenolic acids and carbon dioxide. The acceptable daily intake of (95%) Isoquercitrin and of EMIQ was estimated to be 5.4 and 4.9 mg/kg/day, respectively. Adverse effects of higher doses in rats included mostly (benign) chromaturia; nevertheless some drug interactions may occur due to the modulation of the activity and/or expression of drug metabolizing/transporting systems. With respect to the safety, affordability and beneficial pharmacological activities, highly pure Isoquercitrin is a prospective substance for food supplementation.