Naringenin In Plasma Research Articles

Polyphenols in Almond Skins after Blanching Modulate Plasma Biomarkers of Oxidative Stress in Healthy Humans.

Almond skins are a waste byproduct of blanched almond production. Polyphenols extracted from almond skins possess antioxidant activities in vitro and in vivo. Thus, we examined the pharmacokinetic profile of almond skin polyphenols (ASP) and their effect on measures of oxidative stress. In a randomized crossover trial, seven adults consumed two acute ASP doses (225 mg (low, L) or 450 mg (high, H) total phenols) in skim milk or milk alone. Plasma flavonoids, glutathione peroxidase (GPx), glutathione (GSH), oxidized GSH (GSSG), and resistance of low- density lipoprotein (LDL) to oxidation were measured over 10 h. The H dose increased catechin and naringenin in plasma, with maximum concentrations of 44.3 and 19.3 ng/mL, respectively. The GSH/GSSG ratio at 3 h after the H doses was 212% of the baseline value, as compared to 82% after milk (p = 0.003). Both ASP doses upregulated GPx activity by 26–35% from the baseline at 15, 30, 45, and 120 min after consumption. The in vitro addition of α-tocopherol extended the lag time of LDL oxidation at 3 h after L and H consumption by 144.7% and 165.2% of that at 0 h compared to no change after milk (p ≤ 0.05). In conclusion, ASP are bioavailable and modulate GSH status, GPx activity, and the resistance of LDL to oxidation.

Ocular pharmacokinetics of naringenin eye drops following topical administration to rabbits.

To investigate the ocular pharmacokinetics of 1% naringenin eye drops following topical administration to rabbits. One drop (50 μL) of 1% naringenin eye drops was instilled into both eyes of each rabbit. The animals were sacrificed at predetermined intervals after dosing, and ocular tissues and plasma were then collected. Concentrations of naringenin were analyzed using specific electrospray ionization liquid chromatography-tandem mass spectrometry method, which is proved to be sensitive, specific, precise, and suitable for determination of naringenin in ocular tissues and plasma of rabbits. Ocular exposure to naringenin, based on AUC(0-t), was highest in cornea, followed by aqueous humor, retina, and vitreous body. The Cmax of naringenin in cornea, aqueous humor, vitreous body, and retina were 67945.30 ± 4109.34 ng/g, 1325.69 ± 239.34, 160.52 ± 38.78 ng/mL, and 1927.08 ± 660.77 ng/g at 0.083, 0.75, 0.083, and 0.083 h after topical administration, respectively. The half-lives for these tissues were 9.37, 0.65, 1.17, and 4.62 h, respectively. There was no significant difference between free naringenin and total naringenin in plasma based on Cmax and Tmax. Cmax of total naringenin in plasma at 0.083 h was 35.12 ± 0.54 ng/mL. Measurable concentrations of naringenin were achieved in ocular tissues after topical application in rabbits. Topical instillation of naringenin may be an effective approach in the treatment of posterior section diseases.

Simplified miniaturized ultrasound-assisted matrix solid phase dispersion extraction and high performance liquid chromatographic determination of seven flavonoids in citrus fruit juice and human fluid samples: Hesperetin and naringenin as biomarkers

In the present study, for the first time, a simplified miniaturized ultrasound-assisted matrix solid-phase dispersion (SM-USA-MSPD) method with a different application for liquid matrices was developed to extract different flavonoids (hesperidin, diosmin, eriocitrin, narirutin, naringin, hesperetin and naringenin) from citrus fruit juice and human fluid samples prior to their determination using high performance liquid chromatography (HPLC). Different effective parameters were studied and under the optimum conditions (including sample volume: 150μL; solid phase: silica-based C18, 200mg; eluting solvent: methanol, 500μL; pH: 4; and sonication: 6min; at room temperature), limits of detection and limits of quantification were ranged from 23.3 to 46.8ngmL−1 and 74.8 to 141.5ngmL−1, respectively. Once optimized, analytical performance of the method was studied in terms of linearity (0.074–198.5μgmL−1, r2>0.991), accuracy (recovery=84.6–101.5%), and precision (repeatability: intra-day precision<5.9%, and inter-day precision<7.2%). At the end, SM-USA-MSPD method was successfully applied to estimate the levels of hesperetin and naringenin in plasma and urinary excretion -after ingestion of orange, grapefruit and lime juices- and the obtained results confirmed that these compounds could be used as good biomarkers of citrus fruit juice intake.

Pharmacokinetics of the citrus flavanone aglycones hesperetin and naringenin after single oral administration in human subjects

Hesperetin and naringenin, the aglycones of the flavanone glycosides hesperidin and naringin, occur naturally in citrus fruits. They exert interesting pharmacological properties such as antioxidant, anti-inflammatory, blood lipid and cholesterol lowering and are considered to contribute to health benefits in humans. However, no information is available on the pharmacokinetics of the citrus flavanones hesperetin and naringenin after their oral administration to humans as pure aglycones. Therefore, the objective of the present investigation was the evaluation of the pharmacokinetic parameters of hesperetin and naringenin in plasma and urine, after their single oral administration in humans in the form of solid dispersion capsules, and also to improve the absorption rate of flavanones by using aglycones rather than the naturally occurring glycosides. Six healthy volunteers received orally 135 mg of each compound, hesperetin and naringenin, under fasting conditions. Blood samples were collected at 14 different time points over a 12 h period. Urine was collected over 24 h, in five sequential timed intervals. Plasma and urine hesperetin and naringenin concentrations, after enzymatic hydrolysis of their conjugated forms, were measured using validated high-pressure liquid chromatography methods. Pharmacokinetic parameters for hesperetin and naringenin, such as C(max), T(max), AUC(0-t), AUC(0-infinity), CL/F, V/F, t(1/2), MRT, A(e), A(e)((0-24)), and R(max) were calculated from their plasma or urine concentrations. Pharmacokinetic analysis showed that both hesperetin and naringenin were rapidly absorbed and their concentrations in plasma observed 20 min after dosing and reached a peak in 4.0 and 3.5 h, respectively. The mean peak plasma concentration (C(max)) for hesperetin and naringenin were 825.78+/-410.63 ng/ml (2731.8+/-1358.4 nmol/l) and 2009.51+/-770.82 ng/ml (7386.6+/-2833.4 nmol/l), respectively and the mean AUC(0-infinity) values were 4846.20+/-1675.99 ng h/ml and 9424.52+/-2960.52 ng h/ml for hesperetin and naringenin, respectively. The elimination half-life for hesperetin was found to be 3.05+/-0.91 h and for naringenin 2.31+/-0.40 h, respectively. The mean values of the relative cumulative urinary excretion, as percentage of the administered dose, for hesperetin and naringenin, were found to be 3.26+/-0.44 and 5.81+/-0.81%, respectively. Oral administration of the flavanone aglycones, hesperetin and naringenin, lead to their rapid absorption as their conjugated forms. The cumulative urinary recovery data indicated low bioavailability for both flavanone aglycones, owing to extensive first-pass metabolism partly by cleavage of the C-ring by the enzymes of intestinal bacteria leading to degradation products such as phenolic acids.

LC/MS/MS quantitation assay for pharmacokinetics of naringenin and double peaks phenomenon in rats plasma

A highly sensitive and specific electrospray ionization (ESI) liquid chromatography–tandem mass spectrometry (LC/MS/MS) method for quantitation of naringenin (NAR) and an explanation for the double peaks phenomenon was developed and validated. NAR was extracted from rat plasma and tissues along with the internal standard (IS), hesperidin, with ethyl acetate. The analytes were analyzed in the multiple-reaction-monitoring (MRM) mode as the precursor/product ion pair of m/ z 273.4/151.3 for NAR and m/ z 611.5/303.3 for the IS. The assay was linear over the concentration range of 5–2500 ng/mL. The lower limit quantification was 5 ng/mL, available for plasma pharmacokinetics of NAR in rats. Accuracy in within- and between-run precisions showed good reproducibility. When NAR was administered orally, only little and predominantly its glucuronidation were into circulation in the plasma. There existed double peaks phenomenon in plasma concentration–time curve leading to the relatively slow elimination of NAR in plasma. The results showed that there was a linear relationship between the AUC of total NAR and dosages. And the double peaks are mainly due to enterohepatic circulation.