No abstract

Acacetin, apigenin, chrysin, and pinocembrin are flavonoid aglycones found in foods such as parsley, honey, celery, and chamomile tea. Flavonoids can act as substrates and inhibitors of the CYP3A4 enzyme, a heme containing enzyme responsible for the metabolism of one third of drugs on the market. The aim of this study was to investigate the inhibitory effect of selected flavonoids on the CYP3A4 enzyme, the kinetics of inhibition, the possible covalent binding of the inhibitor to the enzyme, and whether flavonoids can act as pseudo-irreversible inhibitors. For the determination of inhibition kinetics, nifedipine oxidation was used as a marker reaction. A hemochromopyridine test was used to assess the possible covalent binding to the heme, and incubation with dialysis was used in order to assess the reversibility of the inhibition. All the tested flavonoids inhibited the CYP3A4 enzyme activity. Chrysin was the most potent inhibitor: IC50 = 2.5 ± 0.6 µM, Ki = 2.4 ± 1.0 µM, kinact = 0.07 ± 0.01 min−1, kinact/Ki = 0.03 min−1 µM−1. Chrysin caused the highest reduction of heme (94.5 ± 0.5% residual concentration). None of the tested flavonoids showed pseudo-irreversible inhibition. Although the inactivation of the CYP3A4 enzyme is caused by interaction with heme, inhibitor-heme adducts could not be trapped. These results indicate that flavonoids have the potential to inhibit the CYP3A4 enzyme and interact with other drugs and medications. However, possible food–drug interactions have to be assessed clinically.

Acne vulgaris is a common, multifactorial, inflammatory skin disease affecting the pilosebaceous unit. Topical therapy is the first choice in the treatment of mild to moderate acne, and azelaic acid (AZA) is one of the most commonly used drugs. The aim of this study was to evaluate the safety and efficacy of a low-dose azelaic acid nanocrystal (AZA-NC) hydrogel in the treatment of mild to moderate facial acne. The study was designed as a double-blind, randomized controlled trial. Patients were randomized to treatment with AZA-NC hydrogel, 10%, or AZA cream, 20%, administered in quantities of approximately 1 g twice daily for 8 weeks. Efficacy of therapy was measured by the number of lesions and safety by the frequency and severity of adverse events. At week 8, the success rate of treatment with AZA-NC hydrogel, 10%, was 36.51% (p < 0.001) versus 30.37% (p < 0.001) with AZA cream. At week 8, treatment with AZA-NC hydrogel, 10%, resulted in a significant reduction in total inflammatory lesions from baseline of 39.15% (p < 0.001) versus 33.76% (p < 0.001) with AZA cream, and a reduction in non-inflammatory lesions from baseline of 34.58% (p < 0.001) versus 27.96% (p < 0.001) with AZA cream, respectively. The adverse event rate was low and mostly mild.