Quantification of apigenin trimethyl ether in rat plasma by liquid chromatography–tandem mass spectrometry: Application to a pre-clinical pharmacokinetic study

Elhennawy, Mai Gamal; Lin, Hai‐Shu

doi:10.1016/j.jpba.2017.03.070

Cited by 10 publications

(10 citation statements)

References 33 publications

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“…Obviously, aqueous solubility was a barrier to the oral absorption of TAN and solubility enhancing excipient such as RM-β-CD was required to facilitate the delivery of TAN. Similar results have been observed with apigenin trimethyl ether (5,7,4′-trimethoxyflavone), another polymethoxyflavone in our recent study [ 38 ].…”

Section: Resultssupporting

confidence: 90%

“…To prevent blood clotting and sample contamination, 0.3 mL heparin-saline (10 international unit/mL) was infused into the catheter after each intravenous drug administration and blood withdrawal. This reliable model has been commonly applied in our laboratory for pre-clinical pharmacokinetic investigations of various natural products [ 34 , 35 , 36 , 37 , 38 ].…”

Section: Methodsmentioning

confidence: 99%

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Determination of Tangeretin in Rat Plasma: Assessment of Its Clearance and Absolute Oral Bioavailability

Elhennawy

Lin

2017

Pharmaceutics

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Tangeretin (TAN) is a dietary polymethoxylated flavone that possesses a broad scope of pharmacological activities. A simple high-performance liquid chromatography (HPLC) method was developed and validated in this study to quantify TAN in plasma of Sprague-Dawley rats. The lower limit of quantification (LLOQ) was 15 ng/mL; the intra- and inter-day assay variations expressed in the form of relative standard deviation (RSD) were all less than 10%; and the assay accuracy was within 100 ± 15%. Subsequently, pharmacokinetic profiles of TAN were explored and established. Upon single intravenous administration (10 mg/kg), TAN had rapid clearance (Cl = 94.1 ± 20.2 mL/min/kg) and moderate terminal elimination half-life (t1/2 λz = 166 ± 42 min). When TAN was given as a suspension (50 mg/kg), poor but erratic absolute oral bioavailability (mean value < 3.05%) was observed; however, when TAN was given in a solution prepared with randomly methylated-β-cyclodextrin (50 mg/kg), its plasma exposure was at least doubled (mean bioavailability: 6.02%). It was obvious that aqueous solubility hindered the oral absorption of TAN and acted as a barrier to its oral bioavailability. This study will facilitate further investigations on the medicinal potentials of TAN.

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Section: Resultssupporting

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Determination of Tangeretin in Rat Plasma: Assessment of Its Clearance and Absolute Oral Bioavailability

Elhennawy

Lin

2017

Pharmaceutics

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“…We selected these three compounds because they showed greater effectiveness in our previous study carried out in 3T3-L1 [ 18 ] and because their mechanisms of action have been little studied. We carried out the experiment in a range from a physiological dose of 1 μM [ 26 – 32 ] to a high dose of 25 μM.…”

Section: Discussionmentioning

confidence: 99%

Phenolic compounds apigenin, hesperidin and kaempferol reduce in vitro lipid accumulation in human adipocytes

et al. 2017

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BackgroundAdipocytes derived from human mesenchymal stem cells (MSCs) are widely used to investigate adipogenesis. Taking into account both the novelty of these MSCs and the scarcity of studies focused on the effects of phenolic compounds, the aim of the present study was to analyze the effect of apigenin, hesperidin and kaempferol on pre-adipocyte and mature adipocytes derived from this type of cells. In addition, the expression of genes involved in TG accumulation was also measured.MethodsPre-adipocytes were cultured from day 0 to day 8 and mature adipocytes for 48 h with the polyphenols at doses of 1, 10 and 25 µM.ResultsApigenin did not show an anti-adipogenic action. Pre-adipocytes treated with hesperidin and kaempferol showed reduced TG content at the three experimental doses. Apigenin did not modify the expression of the main adipogenic genes (c/ebpβ, c/ebpα, pparγ and srebp1c), hesperidin inhibited genes involved in the three phases of adipogenesis (c/ebpβ, srebp1c and perilipin) and kaempferol reduced c/ebpβ. In mature adipocytes, the three polyphenols reduced TG accumulation at the dose of 25 µM, but not at lower doses. All compounds increased mRNA levels of atgl. Apigenin and hesperidin decreased fasn expression. The present study shows the anti-adipogenic effect and delipidating effects of apigenin, hesperidin and kaempferol in human adipocytes derived from hMSCs. While hesperidin blocks all the stages of adipogenesis, kaempferol only inhibits the early stage. Regarding mature adipocytes, the three compounds reduce TG accumulation by activating, at least in part, lipolysis, and in the case of hesperidin and apigenin, also by reducing lipogenesis.ConclusionsThe present study shows for the first time the anti-adipogenic effect and delipidating effect of apigenin, hesperidin and kaempferol in human adipocytes derived from MSCs for the first time.

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“…Thus, determining the level of a drug candidate and its active metabolites in a biological matrix over time contributes to establishing a better correlation between the administration regimen and the pharmacological response. 16 A previous study by Chen et al 17 kg, but the pharmacokinetic parameters of compound 9 were not calculated. A subsequent study by Sripanidkulchai et al 18 reported the oral pharmacokinetics of compound 9 in rats administered Kaempferia parviflora extract, of which compound 9 was a major component.…”

Section: ■ Introductionmentioning

confidence: 99%

Pharmacokinetics and Metabolites of 12 Bioactive Polymethoxyflavones in Rat Plasma

Qin

Ding

et al. 2021

J. Agric. Food Chem.

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Polymethoxyflavones (PMFs) are a subgroup of flavonoids possessing various health benefits. 3,5,7,4′-Tetramethoxyflavone (1), 5,6,7,4′-tetramethylflavone (2), 3,7,3′,4′-tetramethoxyflavone (3), 5,7,3′,4′-tetramethoxyflavone (4), 5-hydroxy-3,7,2′,4′-tetramethoxyflavone (5), 3,5,7,2′,4′-pentamethoxyflavone (6), 5-hydroxy-3,7,3′,4′-tetramethoxyflavone (7), 3-hydroxy-5,7,3′,4′-tetramethylflavone (8), 3,5,7,3′,4′-pentamethoxyflavone (9), 5-hydroxy-3,7,3′,4′,5′-pentamethoxyflavone (10), 3-hydroxy-5,7,3′,4′,5′-pentamethoxyflavone (11), and 3,5,7,3′,4′,5′-hexamethoxylflavone (12) were 12 bioactive and available PMFs. The aim of this study was to investigate the pharmacokinetic, metabolite, and antitumor activities as well as the structure–pharmacokinetic–antitumor activity relationships of these 12 PMFs to facilitate further studies of their medicinal potentials. The cytotoxicity of PMFs with a hydroxy group toward HeLa, A549, HepG2, and HCT116 cancer cell lines was generally significantly more potent than that of PMFs without a hydroxy group. Compounds 5, 7, 8, 10, and 11 were all undetectable in rat plasma, while compounds 1–4, 6, 9, and 12 were detectable. Both the number and position of hydroxy and methoxy groups played an important role in modulating PMF pharmacokinetics and metabolites.

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Quantification of apigenin trimethyl ether in rat plasma by liquid chromatography–tandem mass spectrometry: Application to a pre-clinical pharmacokinetic study

Cited by 10 publications

References 33 publications

Determination of Tangeretin in Rat Plasma: Assessment of Its Clearance and Absolute Oral Bioavailability

Determination of Tangeretin in Rat Plasma: Assessment of Its Clearance and Absolute Oral Bioavailability

Phenolic compounds apigenin, hesperidin and kaempferol reduce in vitro lipid accumulation in human adipocytes

Pharmacokinetics and Metabolites of 12 Bioactive Polymethoxyflavones in Rat Plasma

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