LAUSR

Propolis is one of the most heterogeneous natural product of plant origin. Research on the flavonoids in propolis has been prompted by their beneficial effects on health. In propolis, pinocembrin (5,7-dihydroxyflavanone) is the flavonoid that is present in the highest concentration. As flavonoids have a broad spectrum of pharmacological activities, more and more biological actions of pinocembrin have been reported, including anti-microbial, antioxidant, anti-inflammatory, vasorelaxant, and neuroprotective effects, etc. The current study focused on investigating the effects of pinocembrin on CYP3A in the rat brain using intracerebral microdialysis. To investigate the pharmacokinetic profiles of midazolam and 1 ′ -hydroxymidazolam in the rat brain before and after intravenous administration of pinocembrin, microdialysates from rat brains were collected and analysed. For microdialysis, a probe was inserted into rats’ paracele and then the animals were administrated either 5% of β-cyclodextrin (control group) or pinocembrin at 3.75, 7.5, 15 mg/kg (treatment groups) via the femoral vein. Rats were then administrated 5 mg/kg midazolam. In the presence of pinocembrin, the pharmacokinetic parameters of midazolam and 1 ′ -hydroxymidazolam varied significantly ( P t 1 / 2 , MRT and Vd were changed from 0.73 ± 0.09 h −1 , 0.96 ± 0.12 h, 1.63 ± 0.16 h and 52.02 ± 8.61 L · kg −1 to 0.55 ± 0.12 h −1 , 1.29 ± 0.19 h, 1.98 ± 0.30 h and 65.1 ± 10.7 L · kg −1 , respectively. The results indicated that pinocembrin induced alterations in the pharmacokinetic profiles of midazolam/ 1 ′ -hydroxymidazolam. Our other experimental data showed that both protein expression and mRNA level of CYP3A were also decreased. So pinocembrin could slow the midazolam metabolism process by inhibiting CYP3A in the rat brain.