Modulation of pregnane X receptor (PXR) and constitutive androstane receptor (CAR) activation by ursolic acid (UA) attenuates rifampin-isoniazid cytotoxicity

• Published in: Phytomedicine (Stuttgart) Vol. 36; pp. 37 - 49
• Main Authors: Chang, Hsiao-Yun, Chen, Chao-Jung, Ma, Wei-Chih, Cheng, Wai-Kok, Lin, Yen-Ning, Lee, Ying-Ray, Chen, Jih-Jung, Lim, Yun-Ping
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.12.2017
• Subjects: agonists; antagonists; catalytic activity; Constitutive Androstane Receptor; cytochrome P-450; Cytochrome P-450 CYP2B6 - genetics; Cytochrome P-450 CYP2B6 - metabolism; Cytochrome P-450 CYP3A - genetics; Cytochrome P-450 CYP3A - metabolism; Cytochrome P450; cytotoxicity; drugs; enzymes; Hep G2 Cells; Hepatocytes - drug effects; hepatoma; Humans; Isoniazid; Isoniazid - toxicity; messenger RNA; neoplasm cells; Pregnane X Receptor; Promoter Regions, Genetic - drug effects; protein synthesis; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - metabolism; Receptors, Steroid - genetics; Receptors, Steroid - metabolism; response elements; rifampicin; Rifampin; Rifampin - pharmacology; transcription (genetics); transcriptional activation; Transfection; Triterpenes - pharmacology; Ursolic Acid; xenobiotics; RXRα; DMSO; Cytochrome P450; HNF4α; Pregnane x receptor; CITCO; PGC-1α; PXR; XREM; UA; Constitutive androstane receptor; ER; DR; TB; CAR; CYP450; DMEs; Ursolic acid; PCN; Rifampin; Isoniazid; SRC-1

Interactions between transcriptional inducers of cytochrome P450 (CYP450) enzymes and therapeutic drugs may be prevented by antagonizing the activation of a nuclear receptor (NR), pregnane X receptor (PXR, NR1I2), thus improving therapeutic efficacy. In the present study, we aim to identify that urs...