Investigation on food packaging polymers: Effects on vegetable oil oxidation.

Polyethylene (PE), polypropylene (PP), polyamide (PA), and polyethylene terephthalate (PET) surfaces and particles were employed to study effects of polymer materials on linseed oil, peanut oil, rapeseed oil and sunflower seed oil oxidation. The surface types of the materials, hydroperoxide content and volatile in oils were determined by contact angle, Fourier transform infrared spectroscopy and gas chromatography-mass spectrometry. Oils on PP surfaces underwent a more rapid oxidation, followed by PA, PE and PET. Except PP sets, this order was consistent with surface hydrophilicity of polymers. Further study using polymer particles avoiding packaging barrier suggested this was probably due to barrier factors. Although PE surfaces allowed oil to have lower content of hydroperoxides, it can promote oil hydroperoxide decomposition into volatile products. Surface types of polymer materials are correlated with oxidation of contacted oil, and these surfaces can also affect the oil secondary oxidation and the degradation of oxidation products.

Influences of Corydalis decumbens on the Activities of CYP450 Enzymes in Rats with a Cocktail Approach.

Corydalis decumbens, a Traditional Chinese Medicine, has been widely used for the alternative and/or complementary therapy of hypertension, arrhythmias rheumatoid arthritis, sciatica, stroke, hemiplegia, paraplegia, and vascular embolism. The aim of this study was to determinate the potential effects of Corydalis decumbens on the five cytochrome P450 (CYP) enzyme activities (CYP1A2, CYP3A4, CYP2C9, CYP2C19, and CYP2D6) by cocktail approach. To evaluate whether concurrent use of Corydalis decumbens interferes with the effect of several prescription drugs, saline (control group) or Corydalis decumbens (XTW group) were administrated via gavage for 7 successive days. A probe cocktail solution (phenacetin, omeprazole, metoprolol, tolbutamide, and midazolam) was given 24 h after the last dose of saline or Corydalis decumbens. A specific and sensitive UHPLC-MS/MS method was validated for the determination of five substrates and their metabolites in control group and XTW group. Our results indicated that Corydalis decumbens could have inductive effects of CYP2C19 and inhibit the activities of CYP1A2 and CYP3A4. However, Corydalis decumbens had no significant influence on CYP2C9 and CYP2D6. The herb-drug interaction should require more attention by careful monitoring and appropriate drug dosing adjustments to the concurrent use of western medications which were metabolized by CYP1A2, CYP2C19, and CYP3A4 in human-Corydalis decumbens, Cytochrome P450, Cocktail, Pharmacokinetics, herb-drug interactions.

Effects of ketoconazole, voriconazole, and itraconazole on the pharmacokinetics of apatinib in rats.

We investigated the effect of azole antifungal drugs (ketoconazole, voriconazole, and itraconazole) on the pharmacokinetics of apatinib in rats. The rats in ketoconazole, voriconazole, and itraconazole groups received single-dose apatinib 30 mg/kg after the oral administration of ketoconazole, voriconazole, and itraconazole, respectively. Co-administration of ketoconazole or voriconazole significantly increased the apatinib Cmax and AUC(0-t) and decreased the clearance. Co-administration of itraconazole did not significantly affect the pharmacokinetics parameters of apatinib. It could be concluded that both ketoconazole and voriconazole significantly increase the exposure of apatinib, and affect the pharmacokinetics of apatinib in rat. Apatinib can be co-administered with itraconazole, but ketoconazole and voriconazole should be avoided if possible or be underwent therapeutic drug monitoring of apatinib. A further clinical study should be conducted to investigate the inhibitory effect of azole antifungal drugs on the apatinib plasma concentration.

Taxifolin inhibits rat and human 11ß-hydroxysteroid dehydrogenase 2.

Taxifolin is a flavonoid in food plants. Kidney 11ß-hydroxysteroid dehydrogenase 2 (11ß-HSD2) is an NAD+-dependent oxidase that inactivates glucocorticoid cortisol (human) or corticosterone (rodents) into biologically inert 11 keto glucocorticoids. The present study investigated the effects of taxifolin on rat and human kidney microsomal 11ß-HSD2. Taxifolin noncompetitively inhibited rat and human 11ß-HSD2 against steroid substrates, with IC50 values of 33.08 and 13.14µM, respectively. Administration of 5 and 10mg/kg taxifolin for 30min ex vivo inhibited 11ß-HSD2 significantly and also in vivo decreased cortisol metabolism, as shown in the significant increase of area under curve (AUC). This result shows that taxifolin is a potent 11ß-HSD2 inhibitor, possibly causing side effects.

Gossypol enantiomers potently inhibit human placental 3ß-hydroxysteroid dehydrogenase 1 and aromatase activities.

Gossypol is a chemical isolated from cotton seeds. It exists as (+) or (-) enantiomer and has been tested for anticancer, abortion-inducing, and male contraception. Progesterone formed from pregnenolone by 3ß-hydroxysteroid dehydrogenase 1 (HSD3B1) and estradiol from androgen by aromatase (CYP19A1) are critical for the maintenance of pregnancy or associated with some cancers. In this study we compared the potencies of (+)- and (-)-gossypol enantiomers in the inhibition of HSD3B1 and aromatase activities as well as progesterone and estradiol production in human placental JEG-3 cells. (+) Gossypol showed potent inhibition on human placental HSD3B1 with IC50 value of 2.3 µM, while (-) gossypol weakly inhibited it with IC50 over 100 µM. In contrast, (-) gossypol moderately inhibited CYP19A1 activity with IC50 of 23 µM, while (+) gossypol had no inhibition when the highest concentration (100 µM) was tested. (+) Gossypol enantiomer competitively inhibited HSD3B1 against substrate pregnenolone and showed mixed mode against NAD(+). (-) Gossypol competitively inhibited CYP19A1 against substrate testosterone. Gossypol enantiomers showed different potency related to their inhibition on human HSD3B1 and CYP19A1. Whether gossypol enantiomer is used alone or in combination relies on its application and beneficial effects.

Simultaneous determination of liensinine, isoliensinine and neferine in rat plasma by UPLC-MS/MS and application of the technique to pharmacokinetic studies.

ETHNOPHARMACOLOGICAL RELEVANCE: The in vivo effects of traditional herbal medicines are generally mediated by multiple bioactive components. The main constituents of Lotus Plumule are alkaloids such as liensinine, isoliensinine and neferine. In this study, a simple, sensitive, and robust analytical method based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) has been developed for the determination of the three alkaloids in rat plasma using carbamazepine as internal standard (IS). MATERIALS AND METHODS: After precipitation of the proteins with acetonitrile, chromatography was performed on an Acquity UPLC BEH C18 column (2.1mm×50mm, 1.7µm particle size) using a gradient elution with 0.1% formic acid in water and acetonitrile. Mass spectrometry involved positive electrospray ionization and multiple reaction monitoring (MRM) of the transitions at m/z 611.7→206.2 for liensinine, 611.3→192.2 for isoliensinine, 625.2→206.1 for neferine and m/z 237.1→194.2 for IS. RESULTS: The method was linear over the concentration range 5-1000ng/mL with a lower limit of quantifof 5ng/mL for each alkaloid. Inter- and intra-day precision (RSD%) were all within 11.4% and the accuracy (RE%) were equal or lower than 10.4%. Recoveries were more than 75.3% and matrix effects were not significant. Stability studies showed that the three alkaloids were stable under a variety of storage conditions. CONCLUSION: The method was successfully applied to a pharmacokinetic study involving intravenous administration of liensinine, isoliensinine and neferine to rats.