The intracellular mechanism of Berberine-induced inhibition of CYP3A4 activity.

Abstract

BACKGROUND\nBerberine (BBR) is an isoquinoline alkaloid extracted from Chinese medicine, exerting various pharmacological effects. BBR is partially metabolized by cytochrome 3A4 (CYP3A4) in vivo. Some reports indicated that BBR could inhibit the activity of CYP3A4. However, the underlying mechanisms are not entirely understood. CYP3A4 is transcriptionally regulated by two nuclear receptors: nuclear transcription X receptor (PXR) and constitutive androstane receptor (CAR). It degraded via the ubiquitin-proteasome system. Hence, we tried to explore the mechanisms of CYP3A4 inhibition on both transcriptive and protein levels.\n\n\nMETHODS\nWestern Blot, RT-PCR, and Co-immunoprecipitation were used to perform the experiments.\n\n\nRESULTS\nOur results showed that BBR inhibited the transcription of CYP3A4 gene by downregulating PXR. In addition, BBR accelerated the degradation of CYP3A4 protein via the polyubiquitination pathway.\n\n\nCONCLUSION\nThese findings may lead to the determination of novel drug-drug interactions with BBR and contribute to the future clinical application of BBR.