Genotoxicity and mutagenicity evaluation of isoquercitrin-γ-cyclodextrin molecular inclusion complex using Ames test and a combined micronucleus and comet assay in rats

Kapoor, Mahendra P.; Moriwaki, Masamitsu; Timm, David H; Satomoto, Kensuke; Minegawa, Kazuyuki

doi:10.2131/jts.47.221

Cited by 4 publications

(3 citation statements)

References 32 publications

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“…Te spectroscopic evaluation of studied favonoid-cyclodextrin inclusion complexes revealed the successful formulation of these compositions [22,23]. Acute, subchronic, Ames, micronucleus, and comet assays support the safe use of these favonoid-cyclodextrin inclusion complexes as food, food additives, and natural pharmaceutical and nutraceutical ingredients [24][25][26]. Also, the bioavailability studies in animals and humans revealed that these favonoidcyclodextrin inclusion complexes are highly bioavailable and could be efective functional favonoid ingredients with potential health benefts in humans [27,28].…”

Section: Introductionmentioning

confidence: 78%

Inhibition of the SARS-CoV-2 Main Protease by Isoquercitrin γ-Cyclodextrin Inclusion Complex Formulations: A Biochemical and In Silico Study

Würtele

Coelho

Gallo

et al. 2023

Journal of Chemistry

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The main protease (Mpro) of SARS-CoV-2 is a well-established drug target for rational drug design of COVID-19 inhibitors. To address the serious challenge of COVID-19, we have performed biochemical inhibition screens with recombinantly expressed SARS-CoV-2 main protease (Mpro). A fluorescent assay was used to identify the flavonoid isoquercitrin as an Mpro inhibitor. Both isoquercitrin encapsulated in γ-cyclodextrin (inclusion complex formulations) and alone inhibited SARS-CoV-2 Mpro. For isoquercitrin, a Ki value of 32 μM (IC50 = 63 μM) was obtained. Isoquercitrin γ-cyclodextrin inclusion complex formulations additionally inhibited Zika virus NS2B-NS3pro leading to an IC50 value of 98 μM. Formulations containing the other flavonoid compounds diosmetin-7-O-glucoside, hesperetin-7-O-glucoside, and naringenin-7-O-glucoside did not inhibit SARS-CoV-2 Mpro. Steady-state kinetics indicate that the inhibition mechanism of Mpro by isoquercitrin is potentially competitive. Molecular modeling studies carried out with MM/PBSA confirm the likely modes of isoquercitrin binding to both proteases. These modeling results can be used in the development of structural analogs of isoquercitrin with better inhibitory profiles and potential candidates for anti-coronavirus drugs. Since the targeted proteases are essential for viral activity, the delivery isoquercitrin-cyclodextrin inclusion complex formulations could be of great interest for the development of future antiviral drugs to target intracellular virus proteins or other components.

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Section: Introductionmentioning

confidence: 78%

Inhibition of the SARS-CoV-2 Main Protease by Isoquercitrin γ-Cyclodextrin Inclusion Complex Formulations: A Biochemical and In Silico Study

Würtele

Coelho

Gallo

et al. 2023

Journal of Chemistry

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“…With oral administration to mice and rats, quercetin consistently did not induce any significant changes in several mutagenicity/ genotoxicity endpoints, such as micronuclei, chromosomal aberrations, sister chromatid exchange, unscheduled DNA synthesis and alkali-labile DNA damage in somatic cells [14]. Furthermore, based on the Ames test and combined in vivo micronucleus and comet assay, there was no induction of in vivo genotoxic potential or indication of any oxidative DNA damage, suggesting the absence of mutagenicity and genotoxicity potential of the isoquercitrin-γ-cyclodextrin (IQC-γCD) inclusion complex in rat liver tissues [15]. On the other hand, a clinical study [16] indicated that total sperm motility was significantly inhibited following exposure to 100, 200 and 400 μM quercetin for 6 and 12 hours in a dose-dependent manner, as compared to the controls (p < 0.05), suggesting that quercetin inhibits sperm functions.…”

Section: Biosafety and Toxicity Profiles Of Quercetinmentioning

confidence: 99%

Preclinical Therapeutic Effects of Quercetin on Gastrointestinal Cancers

Xin Jie Tune,

Seng Wu,

Mac Guad

et al. 2024

Quercetin - Effects on Human Health [Working Title]

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Gastrointestinal (GI) cancers were included in the top 10 most common cancers in 2020. Future incidences are expected to rise due to the varying risk factors and aetiologies. With high incidences and mortality rates, current cancer treatments fail to reduce mortality and morbidity in GI cancer patients. A large part of cancer research has been geared towards targeted and personalized medicine, although effective, it may not be the most cost-friendly and feasible option to treat patients from varying socioeconomic backgrounds. Hence, natural compounds may present as an attractive alternative treatment in the management of GI cancers. Quercetin is a well-known flavonoid compound, found in almost all fruits and vegetables. It has also been widely studied for its anticancer properties, such as anti-oxidative, anti-inflammatory, anti-proliferative and anti-angiogenic properties. In this chapter, the authors discuss the potential of quercetin in treating GI cancers, which includes the biosafety and toxicity of quercetin, applications of quercetin in common GI cancers, such as gastric, hepatic, colorectal, pancreatic and oesophageal cancers, along with the corresponding molecular mechanisms. The authors also present evidences of quercetin as an adjuvant therapeutic agent with other anticancer drugs.

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“…Any chemical substance (compounds) that is capable of causing the organism to mutate is considered mutagenic and possibly carcinogenic [2,3]. Evaluation of herbal medicine products which contains polychemical substances (compounds) for their mutagenic potential has not been a common practice Worldwide but of late, several products have been evaluated for their mutagenic potentials [4][5][6][7][8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Mutagenic Potential of Artavol® Using the Ame’s Test

Oloro,

Kasazza,

P’okello

et al. 2024

EJMP

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Background: The worldwide increase in the use of herbal medicinal - products calls for their safety testing to protect the public from unintended hazardous effects. However, most are not tested, putting the public at risk. The modified Ames ISO test is a useful resource for determining the mutagenic potential of medicinal products and was used in this study to determine the safety of an herbal tea like Artavol®. Methods: This study used Ame's Modified ISO test to analyze aqueous extract of Artavol®, in a Level II biosafety cabinet. Artavol® was extracted using the infusion method 1,2, freeze dried, diluted to concentrations of 125µg, 250µg, and 500µg and used in the study. Mutagenicity was tested by culturing Salmonella typhimurium TA98 and TA100. Results were considered by observing colour change in the wells of the microtitre plates from purple to yellow indicating mutation. Valid results were determined by comparing negative and positive control plates after 3 days of incubation, with positive results showing a color change from purple to yellow. Results: Colour changes were not observed in all wells containing 125µg, 250µg, and 500µg of Artavol® up to day 3, while negative control showed color changes equivalent to 80% for TA98 and 70% for TA100. Conclusion: Aqueous extract of Artavol® is not mutagenic. Further safety test such as sub-chronic toxicity study ad teratogenicity studies are recommended to provide more safety data on the product.

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Genotoxicity and mutagenicity evaluation of isoquercitrin-γ-cyclodextrin molecular inclusion complex using Ames test and a combined micronucleus and comet assay in rats

Cited by 4 publications

References 32 publications

Inhibition of the SARS-CoV-2 Main Protease by Isoquercitrin γ-Cyclodextrin Inclusion Complex Formulations: A Biochemical and In Silico Study

Inhibition of the SARS-CoV-2 Main Protease by Isoquercitrin γ-Cyclodextrin Inclusion Complex Formulations: A Biochemical and In Silico Study

Preclinical Therapeutic Effects of Quercetin on Gastrointestinal Cancers

Evaluation of the Mutagenic Potential of Artavol® Using the Ame’s Test

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