CYP3A4型
小檗碱
孕烷X受体
化学
蛋白酶体
泛素
受体
药理学
体内
转录因子
核受体
生物化学
细胞色素P450
生物
基因
酶
生物技术
作者
Pan-Feng Feng,Long-Xun Zhu,Jing Jie,Pengxiang Yang,Xia Chen
标识
DOI:10.2174/1381612827666210715155809
摘要
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.Western Blot, RT-PCR and Co-immunoprecipitation were used to perform the experiments.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.These findings may lead to the determination of novel drug-drug interactions with BBR, and contribute to future clinical application of BBR.
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