Effects of curcuma comosa roxb. Extract on the expression of cyp450s in immortalized hepatocyte-like cells (imhc)

Abstract

Hepatocytes are the most abundant liver cells that produce biotransformation enzymes, including phase I metabolism enzymes and cytochrome P450s (CYP450s). These enzymes are induced or suppressed by several drugs and chemicals. Here, immortalized hepatocyte-like cells (imHC) were applied as a novel hepatocyte to study the CYP450 enzyme expression induced by a Thai folk herb, Curcuma comosa Roxb. (C. comosa). The results demonstrated that the mRNA expression levels were dependent on cell cultivation conditions, the extract's concentration, and the duration of treatment. In the 3-day cultivation, 1 µg/mL C. comosa extract upregulated the mRNA expression levels of CYP1A1, CYP1A2, CYP2B6, CYP2C9, CYP2D6, CYP2E1 and CYP3A4 in imHC, after treatment for 48 h, which was comparable to the expression levels of those genes in HepG2 cells. In addition, C. comosa increased CYP3A4 protein expression in both imHC and HepG2 cells. Furthermore, 1 µg/mLC. comosa could neutralize erythromycin's inhibitory effect, a specific CYP3A4 inhibitor, on CYP3A4 enzyme activity. In conclusion, imHC exhibited several detoxification enzymes, and this cell could be used to replace hepatic carcinoma cells in hepatotoxic studies. The function of C. comosa as a CYP enzyme-inducing agent indicates a promising treatment for the prevention of drug-induced hepatotoxicity by activating detoxification enzymes.