In this study, researchers from the Central South University in China investigated the effect of a Chinese herbal formula Shaoyao Gancao decoction (SGD) and its constituent herbs on the pregnane X receptor (PXR)-mediated transcriptional regulation of cytochrome P450 3A4 (CYP3A4) and drug transporter multi-drug resistance protein 1 (MDR1) in vitro. The results of their study, which highlighted the in vitro mechanism by which SGD regulates drug metabolic enzymes and drug transporters, were published in the journal BMC Complementary and Alternative Medicine.
SGD is often used as an adjuvant to chemotherapeutic agents in the treatment of cancer.
Due to the herb-drug interactions, the researchers wished to explore the alternations of drug metabolic enzyme and drug transporters induced by SGD.
They co-transfected the dual luciferase reporter gene system containing the hPXR expression plasmid and the reporter gene plasmid of either CYP3A4 or MDR1 in HepG2 and Caco2 cells.
They used a Dual-luciferase reporter assay kit to determine luciferase activities and assessed the gene expression of CYP3A4 and MDR1 in the hPXR-transfected LS174T cells using real-time qPCR.
They evaluated the contribution of the constituent herbs of SGD to the regulation of CYP3A4 and MDR1.
The researchers found that SGD, shaoyao, and gancao increased the promoter activities of CYP3A4 and MDR1 in a concentration-dependent manner in vitro.
SGD, shaoyao, and gancao also up-regulated CYP3A4 and MDR1 mRNA in hPXR-transfected LS174T cells.
The researchers found that gancao treatment resulted in significantly higher levels of metabolic enzyme and drug transporters compared with shaoyao treatment.
Based on these results, the researchers concluded that SGD enhances the expression of CYP3A4 and MDR1 via the PXR pathway with gancao as the main contributor to this acitvity.
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Journal Reference:
Feng D, Tang T, Fan R, Luo J, Cui H, Wang Y, Gan P. GANCAO (GLYCYRRHIZAE RADIX) PROVIDES THE MAIN CONTRIBUTION TO SHAOYAO-GANCAO DECOCTION ON ENHANCEMENTS OF CYP3A4 AND MDR1 EXPRESSION VIA PREGNANE X RECEPTOR PATHWAY IN VITRO. BMC Complementary and Alternative Medicine. 29 December 2018;18(1):345. DOI: 10.1186/s12906-018-2402-7