Title:The Intracellular Mechanism of Berberine-Induced Inhibition of CYP3A4 Activity
Volume: 27
Issue: 40
Author(s): Pan-Feng Feng, Long-Xun Zhu, Jing Jie, Peng-Xiang Yang and Xia Chen*
Affiliation:
- Department of Pharmacy, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Jiangsu Province, 226001,China
Keywords:
Berberine, CYP3A4, transcription, ubiquitination degradation, X receptor (PXR), RT-PCR.
Abstract:
Background: Berberine (BBR) is an isoquinoline alkaloid extracted from the Chinese medicine,
exerting a variety of 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 completely understood. CYP3A4 is reported to be transcriptionally regulated by two nuclear receptors,
nuclear transcription X receptor (PXR) and constitutive androstane receptor (CAR), and degraded via
the ubiquitin-proteasome system. Hence, we tried to explore the mechanisms of CYP3A4 inhibition on both
transcriptive and protein levels.
Methods: Western Blot, RT-PCR and Co-immunoprecipitation were used to perform the experiments.
Results: Our results showed that BBR inhibited the transcription of CYP3A4 gene by downregulating PXR. In
addition, BBR accelerated the degradation of CYP3A4 protein via polyubiquitination pathway.
Conclusion: These findings may lead to the determination of novel drug-drug interactions with BBR, and contribute
to future clinical application of BBR.
