UHPLC-MS/MS Determination, Pharmacokinetic, and Bioavailability Study of Taxifolin in Rat Plasma after Oral Administration of its Nanodispersion

Yang, Chun Juan; Wang, Zhi Bin; Mi, Ying Ying; Gao, Ming; Lv, Jin Nan; Meng, Yongdong; Yang, Bing; Kuang, Hai Xue

doi:10.3390/molecules21040494

Cited by 37 publications

(17 citation statements)

References 22 publications

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“…A C ring with a C2=C3 double bond is the major structural difference between quercetin and taxifolin. An experiment in rats shows that the bioavailability of quercetin (4.11%) after oral administration is much higher than that of oral administration of taxifolin (0.49%) [55,56]. Furthermore, lactase-phlorizin hydrolase can effectively hydrolyze quercetin and produce easily absorbed aglycone in the intestinal lumen, however, rutin cannot be hydrolyzed by intestinal β-glucosidases, and is only metabolized by microorganisms in the cecum and colon [57].…”

Section: Discussionmentioning

confidence: 99%

Comparison of In Vitro and In Vivo Antioxidant Activities of Six Flavonoids with Similar Structures

et al. 2020

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The in vitro and in vivo antioxidant activities of six flavonoids with similar structures, including epicatechin (EC), epigallocatechin (EGC), procyanidin B2 (P), quercetin (Q), taxifolin (T), and rutin (R) were compared. The structures of the six flavonoids and their scavenging activities for 2,2-diphenyl-1-picrylhydrazyl (DPPH•) and 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+) radicals were closely related. The flavonoids decreased serum contents of malondialdehyde (MDA) and nitric oxide (NO), and increased serum total antioxidative capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) levels to different degrees in d-galactose-treated mice. The changes in mRNA expression of liver GSH-Px1, CAT, SOD1, and SOD2 by d-galactose were dissimilarly restored by the six flavonoids. Moreover, the six flavonoids differentially prevented the inflammatory response caused by oxidative stress by inhibiting interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α levels, and restoring IL-10 levels. These six flavonoids from two subclasses revealed the following antioxidant capability: P > EC, EGC > EC, Q > T, Q > R. Our results indicate that (1) the pyrogallol, dimerization, and C2=C3 double bonds of flavonoids enhanced antioxidant activity and (2) the C3 glycosylation of flavonoids attenuated antioxidant capacity.

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Section: Discussionmentioning

confidence: 99%

Comparison of In Vitro and In Vivo Antioxidant Activities of Six Flavonoids with Similar Structures

et al. 2020

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“…However, additional studies on animal models of skin cancer should be further investigated. The nanodispersion of TAX can be used via oral administration, which could improve the bioavailability of taxifolin significantly [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Taxifolin Activates the Nrf2 Anti-Oxidative Stress Pathway in Mouse Skin Epidermal JB6 P+ Cells through Epigenetic Modifications

Kuang

Tang

Zhang

et al. 2017

IJMS

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Nuclear factor erythroid-2 related factor 2 (Nrf2) is a vital transcription factor that regulates the anti-oxidative defense system. Previous reports suggested that the expression of the Nrf2 gene can be regulated by epigenetic modifications. The potential epigenetic effect of taxifolin (TAX), a potent cancer chemopreventive agent, in skin cancer chemoprotection is unknown. In this study, we investigated how Nrf2 is epigenetically regulated by TAX in JB6 P+ cells. TAX was found to inhibit the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced colony formation of JB6 P+ cells. TAX induced antioxidant response element (ARE)-luciferase activity in HepG2-C8 cells and up-regulated mRNA and protein levels of Nrf2 and its downstream genes heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1), in JB6 P+ cells. Furthermore, bisulfite genomic sequencing revealed that TAX treatment reduces the methylation level of the first 15 CpGs sites in the Nrf2 promoter. Western blotting showed that TAX inhibits the expression levels of DNA methyltransferase (DNMT) and histone deacetylase (HDAC) proteins. In summary, our results revealed that TAX can induce expression of Nrf2 and its downstream target genes in JB6 P+ cells by CpG demethylation. These finding suggest that TAX may exhibit a skin cancer preventive effect by activating Nrf2 via an epigenetic pathway.

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“…Additional investigation will greatly help to confirm if the mode of action of taxifolin involves a direct interaction with the SRA domain. Nanoformulation-based technologies that improve the bioefficacy [ 114 ] are expected to play a greater role in the evaluation of natural products particularly the anti-cancer properties of taxifolin which are sometimes eclipsed in an experimental setting due to solubility, bioavailability and pharmacokinetic issues [ 115 , 116 ].…”

Section: Structure-based Studies Indicate Luteolin and Taxifolin Are mentioning

confidence: 99%

Targeting the SET and RING-associated (SRA) domain of ubiquitin-like, PHD and ring finger-containing 1 (UHRF1) for anti-cancer drug development

2018

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Ubiquitin-like containing PHD Ring Finger 1 (UHRF1) is a multi-domain protein with a methyl-DNA binding SRA (SET and RING-associated) domain, required for maintenance DNA methylation mediated by DNMT1. Primarily expressed in proliferating cells, UHRF1 is a cell-cycle regulated protein that is required for S phase entry. Furthermore, UHRF1 participates in transcriptional gene regulation by connecting DNA methylation to histone modifications. Upregulation of UHRF1 may serve as a biomarker for a variety of cancers; including breast, gastric, prostate, lung and colorectal carcinoma. To this end, overexpression of UHRF1 promotes cancer metastasis by triggering aberrant patterns of DNA methylation, and subsequently, silencing tumor suppressor genes. Various small molecule effectors of UHRF1 have been reported in the literature, although the mechanism of action may not be fully characterized. Small molecules that potentially bind to the SRA domain may affect the ability of UHRF1 to bind hemimethylated DNA; thereby reducing aberrant DNA methylation. Therefore, in a subset of cancers, small molecule UHRF1 inhibitors may restore normal gene expression and serve as useful anti-cancer therapeutics.

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UHPLC-MS/MS Determination, Pharmacokinetic, and Bioavailability Study of Taxifolin in Rat Plasma after Oral Administration of its Nanodispersion

Cited by 37 publications

References 22 publications

Comparison of In Vitro and In Vivo Antioxidant Activities of Six Flavonoids with Similar Structures

Comparison of In Vitro and In Vivo Antioxidant Activities of Six Flavonoids with Similar Structures

Taxifolin Activates the Nrf2 Anti-Oxidative Stress Pathway in Mouse Skin Epidermal JB6 P+ Cells through Epigenetic Modifications

Targeting the SET and RING-associated (SRA) domain of ubiquitin-like, PHD and ring finger-containing 1 (UHRF1) for anti-cancer drug development

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