Application of a liquid chromatography–tandem mass spectrometry method to the pharmacokinetics, bioavailability and tissue distribution of neohesperidin dihydrochalcone in rats

Wang, Xianqin; Pan, Yu; Ma, Jianshe; Shi, Shaohua; Zheng, Xiaochun; Xiang, Zheng

doi:10.3109/00498254.2013.861950

Cited by 6 publications

(7 citation statements)

References 9 publications

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“…The reactions occurred at the hydroxyls of the C-2', C-4', and C-6' position. Wang et al (2014) estimated a plasma half-life of 1.0 AE 0.2 h and a volume of distribution of 1.2 AE 0.49 L/kg.…”

Section: Summary and Conclusion On Admementioning

confidence: 99%

“…In vivo ADME data are only available from two studies in rats, with one assessing metabolites as well as the parent compound. Wang et al (2014) estimated the systemic availability of neohesperidine dihydrochalcone in rats as being 21.8%. Zhang et al (2021) identified 19 components in the urine, among them the parent compound besides several metabolites, mostly glucuronides, sulfates and other conjugates which were also formed after hydrolysis of neohesperidine dihydrochalcone to hesperetin dihydrochalcone.…”

Section: Summary and Conclusion On Admementioning

confidence: 99%

“…The plasma concentration–time profile of neohesperidine dihydrochalcone (purity > 98%) was analysed in six rats following oral administration of 20 mg/kg neohesperidine dihydrochalcone and in additional six rats following intravenous administration of 2 mg/kg neohesperidine dihydrochalcone, in both cases after withdrawal of diet 12 h prior to administration (Wang et al., 2014). The analytical methodology was validated following FDA guidelines with respect to specificity, recovery, within‐ and between‐day, precision, lower LOD, LLOQ and sample stability (US Food and Drug Administration, 2001).…”

Section: Assessmentmentioning

confidence: 99%

“…Wang et al. (2014) estimated the systemic availability of neohesperidine dihydrochalcone in rats as being 21.8%. Zhang et al.…”

Section: Assessmentmentioning

confidence: 99%

“…Wang et al. (2014) estimated a plasma half‐life of 1.0 ± 0.2 h and a volume of distribution of 1.2 ± 0.49 L/kg.…”

Section: Assessmentmentioning

confidence: 99%

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Re‐evaluation of neohesperidine dihydrochalcone (E 959) as a food additive

Younes¹,

Aquilina²,

Castle³

et al. 2022

EFS2

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The present opinion deals with the re‐evaluation of neohesperidine dihydrochalcone (E 959) when used as a food additive. It is obtained by catalytic hydrogenation of a flavanone – neohesperidine – which is naturally occurring and thus isolated by alcohol extraction in bitter oranges (Citrus aurantium). Based on in vivo data in rat, neohesperidine dihydrochalcone is likely to be absorbed, also in humans, and to become systemically available. It does not raise a concern regarding genotoxicity. The toxicity data set consisted of studies on subchronic and prenatal developmental toxicity. No human studies were available. The data set was considered sufficient to derive a new acceptable daily intake (ADI). Based on the weight of evidence (WoE) analysis, the Panel considered unlikely that neohesperidine dihydrochalcone would lead to adverse effects on health in animals in the dose ranges tested. The Panel also considered that a carcinogenicity study was not warranted and that the lack of human data did not affect the overall confidence in the body of evidence. The Panel derived an ADI of 20 mg/kg bodyweight (bw) per day based on a no observed adverse effect level (NOAEL) of 4,000 mg/kg bw per day from a 13‐week study in rat, applying the standard default factors of 100 for inter‐ and intraspecies differences and of 2 for extrapolation from subchronic to chronic exposure. For the refined brand‐loyal exposure assessment scenario, considered to be the most appropriate for the risk assessment, the exposure estimates at the mean ranged from < 0.01 to 0.09 mg/kg bw per day and at the 95th percentile (P95) from 0.01 to 0.24 mg/kg bw per day. Considering the derived ADI of 20 mg/kg bw per day, the exposure estimates were below the reference value in all age groups. Therefore, the Panel concluded that dietary exposure to the food additive neohesperidine dihydrochalcone (E 959) at the reported uses and use levels would not raise a safety concern.

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Section: Summary and Conclusion On Admementioning

confidence: 99%

Section: Summary and Conclusion On Admementioning

confidence: 99%

Section: Assessmentmentioning

confidence: 99%

“…Wang et al. (2014) estimated the systemic availability of neohesperidine dihydrochalcone in rats as being 21.8%. Zhang et al.…”

Section: Assessmentmentioning

confidence: 99%

“…Wang et al. (2014) estimated a plasma half‐life of 1.0 ± 0.2 h and a volume of distribution of 1.2 ± 0.49 L/kg.…”

Section: Assessmentmentioning

confidence: 99%

See 3 more Smart Citations

Re‐evaluation of neohesperidine dihydrochalcone (E 959) as a food additive

Younes¹,

Aquilina²,

Castle³

et al. 2022

EFS2

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Metabolomic Analysis and in Vitro Investigation of the Biological Properties of a By‐Product Derived from Vicia faba

Raoof,

El‐Anssary,

Younis

et al. 2023

Chemistry & Biodiversity

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By‐products from plant sources are recently regarded as a valuable source of bioactive compounds. In this regard, the present study aims to assess the bioactivities of the 70% MeOH extract obtained from Vicia faba peels and analyze its metabolomic profile. Acetylcholinesterase and carbohydrate metabolizing enzymes inhibitory activities of the plant extract were assayed using quantitative colorimetric tests. Antioxidant activity was estimated by DPPH assay, and cytotoxic activity was evaluated against normal fibroblast skin cells (1‐ BJ1). Ninety‐one metabolites were tentatively identified using ultra‐high‐performance liquid chromatography (UHPLC) hyphenated with quadrupole‐time‐of‐flight tandem mass spectrometry (QTOF‐MS). Most of these compounds were described for the first time in the plant. In addition, catechin, rutin, quercitrin, and rhamnetin were isolated from the plant extract. The plant extract and the isolated compounds possessed no cytotoxic activity on (1‐ BJ1), while they exhibited anticholinesterase with the highest activity for 70% MeOH extract (IC50= 120.11mg/L), antioxidant potential with the highest activity for rutin (90.54±0.73%), and carbohydrate metabolizing inhibitory activities with the highest activity for rutin. These discoveries imply that V. faba peels might serve as an efficient antioxidant, exhibit anticholinesterase properties, and have the potential for use in managing diabetes, all while avoiding cytotoxicity in normal cells.

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