A Cocktail Approach Toward Tunable Organic Afterglow Systems

In this work, a cocktail approach toward tunable organic long-lived luminescence materials in solid, solution, and gel states is proposed. The tunable long-lived luminescence (τ > 0.7 s) is realized by controlling the energy transfer via manipulating the photo-induced isomerization of the energy acceptor (5). The afterglow can be regulated between blue and yellow emission upon irradiation of UV or visible light. And the “apparent lifetime” for the long-lived fluorescence is the same as the lifetime of the energy donor. The function is relying on the simple radiative energy transfer (reabsorption) between a long-lived phosphorescence and a highly efficient fluorescent isomer (5b), rather than the complicated communication between the excited state of the molecules such as Förster resonance energy transfer or Dexter energy transfer. The simple working principle endows this strategy with huge universality, flexibility, and operability. This work offers an extremely simple, feasible, and universal way to construct tunable afterglow materials in solid, solution, and gel states.

Effects of Shaoyao-Gancao-Fuzi Decoction on the Pharmacokinetics of CYP3A4-Mediated Tofacitinib in Rats

Background: The combination of traditional Chinese medicine and western medicine is commonly accepted in clinics in China. Shaoyao-Gancao-Fuzi decoction (SGFD) has been extensively used to dispel wind, eliminate dampness and treat paralysis. Tofacitinib is approved for the treatment of rheumatoid arthritis. SGFD and tofacitinib could be used together for the treatment of rheumatoid arthritis.Methods: A cocktail approach was employed to assess the effects of SGFD on the activities of CYP450s. After pretreatment for 2 weeks with SGFD, a cocktail solution was given to rats 24 h after the last dose of saline or SGFD. Additionally, the pharmacokinetic profiles of oral administration of tofacitinib in rats, with or without SGFD pre-treatment were investigated.Results: The results showed that SGFD could induce the activity of CYP1A2 and inhibit the activity of CYP3A4. Furthermore, SGFD could significantly affect the pharmacokinetics of tofacitinib. Compared with control group, the AUC0-∞ of tofacitinib was increased from 13669.53 ± 4986.83 to 28706.69 ± 9563.13 ng/mL*h (p < 0.01), and the Cmax was increased from 8359.66 ± 1512.22 to 11332.51 ± 2791.90 ng/mL (p < 0.05).Conclusions: The system exposure of tofacitinib was increased by SGFD. The mechanism might be through inhibiting the activity of CYP3A4 and reducing the metabolism of tofacitinib in rats. The study will provide better guidance for the safe clinical use of SGFD and tofacitinib.

HPLC-MS/MS Analysis of Aconiti Lateralis Radix Praeparata and Its Combination with Red Ginseng Effect on Rat CYP450 Activities Using the Cocktail Approach

Red ginseng is often combined with Aconiti Lateralis Radix Praeparata to reduce alkaloids-related toxicity of the latter. Such herb-pairing also results in better therapeutic effect in heart failure, as compared to the singular use of either herb. The purpose of this study was to investigate the effect of Aconiti Lateralis Radix Praeparata and its combination with red ginseng on the activities of CYP450 enzymes in rats. A sensitive and reliable HPLC-MS/MS method was established and validated for the simultaneous determination of eight probe drugs, phenacetin (CYP1A2), tolbutamide (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), dapsone (CYP3A4), 7-hydroxycoumarin (CYP2A6), bupropion (CYP2B6), and amodiaquine (CYP2C8), in rat plasma using diazepam as internal standard (IS). The chromatographic separation was performed on a Waters XBridge™ C18 column (2.1 mm × 100 mm, 3.5 μm) using a gradient elution with the mobile phase consisting of acetonitrile and water (containing 0.1% formic acid) at a flow rate of 0.3 mL/min. The method was successfully applied in evaluating the effect of Aconiti Lateralis Radix Praeparata and red ginseng on the activities of CYP450 enzymes. The pharmacokinetic results of the eight probe drugs suggested that Aconiti Lateralis Radix Praeparata may inhibit the activity of CYP2A6, CYP2C19, CYP2B6, CYP1A2, CYP3A4, and CYP2C9 enzymes in rats. Comparison between the two groups, Aconiti Lateralis Radix Praeparata combined with red ginseng and Aconiti Lateralis Radix Praeparata, indicated that red ginseng may inhibit the activity of CYP2D6 and CYP2B6 enzymes while inducing the activity of CYP1A2, CYP3A4, and CYP2C9 enzymes.