In vivo study of dihydroquercetin genotoxicity

Жанатаев, А. К.; Кулакова, А. В.; Насонова, В.В.; Дурнев, А. Д.

doi:10.1007/s10517-008-0085-7

Cited by 15 publications

(8 citation statements)

References 5 publications

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“…The safety profile of taxifolin has been studied previously [7, 79]. Consistent with these reports, animal survival rates were comparable among vehicle- or taxifolin-treated WT and Tg-SwDI mice groups (Fig.…”

Section: Resultssupporting

confidence: 85%

Taxifolin inhibits amyloid-β oligomer formation and fully restores vascular integrity and memory in cerebral amyloid angiopathy

Saitô

Yamamoto

Maki

et al. 2017

acta neuropathol commun

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Cerebral amyloid angiopathy (CAA) induces various forms of cerebral infarcts and hemorrhages from vascular amyloid-β accumulation, resulting in acceleration of cognitive impairment, which is currently untreatable. Soluble amyloid-β protein likely impairs cerebrovascular integrity as well as cognitive function in early stage Alzheimer’s disease. Taxifolin, a flavonol with strong anti-oxidative and anti-glycation activities, has been reported to disassemble amyloid-β in vitro but the in vivo relevance remains unknown. Here, we investigated whether taxifolin has therapeutic potential in attenuating CAA, hypothesizing that inhibiting amyloid-β assembly may facilitate its clearance through several elimination pathways. Vehicle- or taxifolin-treated Tg-SwDI mice (commonly used to model CAA) were used in this investigation. Cognitive and cerebrovascular function, as well as the solubility and oligomerization of brain amyloid-β proteins, were investigated. Spatial reference memory was assessed by water maze test. Cerebral blood flow was measured with laser speckle flowmetry and cerebrovascular reactivity evaluated by monitoring cerebral blood flow changes in response to hypercapnia. Significantly reduced cerebrovascular pan-amyloid-β and amyloid-β1-40 accumulation was found in taxifolin-treated Tg-SwDI mice compared to vehicle-treated counterparts (n = 5). Spatial reference memory was severely impaired in vehicle-treated Tg-SwDI mice but normalized after taxifolin treatment, with scoring similar to wild type mice (n = 10–17). Furthermore, taxifolin completely restored decreased cerebral blood flow and cerebrovascular reactivity in Tg-SwDI mice (n = 4–6). An in vitro thioflavin-T assay showed taxifolin treatment resulted in efficient inhibition of amyloid-β1-40 assembly. In addition, a filter trap assay and ELISA showed Tg-SwDI mouse brain homogenates exhibited significantly reduced levels of amyloid-β oligomers in vivo after taxifolin treatment (n = 4–5), suggesting the effects of taxifolin on CAA are attributable to the inhibition of amyloid-β oligomer formation. In conclusion, taxifolin prevents amyloid-β oligomer assembly and fully sustains cognitive and cerebrovascular function in a CAA model mice. Taxifolin thus appears a promising therapeutic approach for CAA.

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Section: Resultssupporting

confidence: 85%

Taxifolin inhibits amyloid-β oligomer formation and fully restores vascular integrity and memory in cerebral amyloid angiopathy

Saitô

Yamamoto

Maki

et al. 2017

acta neuropathol commun

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“…The experimental substance did not affect antibody-forming cells of the spleen or alter the hemagglutinin titer in the serum or result in any delayed-type hypersensitivity or graft versus host reactions. Previous studies reported by Zhanataev et al, 29 that assessed DHQ’s genotoxicity in the chromosome aberration test and the DNA-comet assay, found a lack of evidence of the compound’s genotoxicity. In their studies, DHQ was administered 5 times at 0.15 or 1.5 mg/kg, or in a single dose of 15, 150, or 2000 mg/kg, in 8- to 12-week-old male and female C57B1/6 mice (18-20 g) and found to induce no DNA damage in bone marrow, or blood, liver, and rectal cells.…”

Section: Discussionmentioning

confidence: 92%

Toxicological and Genotoxicity Assessment of a Dihydroquercetin-Rich Dahurian Larch Tree (Larix gmelinii Rupr) Extract (Lavitol)

Schauss

Tselyico

Kuznetsova³

et al. 2015

Int J Toxicol

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Safety assessment is reported of an orally ingested dihydroquercetin-rich extract (Lavitol) derived from the Dahurian larch tree, used as a food additive and as a dietary supplement ingredient. Dihydroquercetin, a potent antioxidant, is also known as taxifolin. The results of genotoxicity and toxicological tests (Comet assay, micronucleus test in human lymphocytes, chromosomal aberration test, subacute 7-day oral toxicity study, subchronic 90-day toxicology study with histopathologies, and, prenatal and postnatal developmental toxicity studies) on the extract provide further support for the safety of its consumption as a food supplement and food additive.

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“…As genotoxicity [41] and mutagenicity [42] of TXF have been demonstrated to be very low, this phytochemical is considered to be a highly safe hypoglycemic and hypouricemic biofactor.…”

Section: Discussionmentioning

confidence: 99%

Antidiabetic Effect of Taxifolin in Cultured L6 Myotubes and Type 2 Diabetic Model KK-Ay/Ta Mice with Hyperglycemia and Hyperuricemia

Kondo

Adachi

Yoshizawa

et al. 2021

CIMB

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Muscle is the largest tissue in our body and plays an important role in glucose homeostasis and hence diabetes. In the present study, we examined the effects of taxifolin (TXF) on glucose metabolism in cultured L6 muscle cells (myotubes) and in type 2 diabetic (T2D) model KK-Ay/Ta mice. TXF dose-dependently increased glucose uptake (GU) in L6 myotubes under the condition of insulin absence. This increase in GU was partially, but significantly canceled by TXF treatment in combination with either LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3K), which phosphorylates protein kinase B (Akt) or Compound C, an inhibitor of 5’-adenosine monophosphate-activated protein kinase (AMPK). Furthermore, TXF was demonstrated to activate (=phosphorylate) both Akt and AMPK, and promote glucose transporter 4 (GLUT4) translocation to the plasma membrane from cytosol of L6 myotubes via both PI3K/Akt and AMPK signaling pathways. Based on these in vitro findings, we conducted an in vivo experiment in KK-Ay/Ta mice with hyperglycemia and hyperuricemia. Fasting plasma glucose, insulin, uric acid levels and an index of insulin resistance (HOMA-IR) increased significantly in the T2D model mice compared with normal ones. Such rises in the T2D state were significantly suppressed by oral administration of TXF for four weeks. These results suggest that TXF is a potent antihyperglycemic and antihyperuricemic phytochemical in the T2D state.

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In vivo study of dihydroquercetin genotoxicity

Cited by 15 publications

References 5 publications

Taxifolin inhibits amyloid-β oligomer formation and fully restores vascular integrity and memory in cerebral amyloid angiopathy

Taxifolin inhibits amyloid-β oligomer formation and fully restores vascular integrity and memory in cerebral amyloid angiopathy

Toxicological and Genotoxicity Assessment of a Dihydroquercetin-Rich Dahurian Larch Tree (Larix gmelinii Rupr) Extract (Lavitol)

Antidiabetic Effect of Taxifolin in Cultured L6 Myotubes and Type 2 Diabetic Model KK-Ay/Ta Mice with Hyperglycemia and Hyperuricemia

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