Aims: Calculus Bovis Sativus (CBS) shares similar pharmacological effects with Calculus Bovis like relieving hepatobiliary diseases. This study aims to investigate the effect and mechanism of CBS on 17α-ethynylestradiol (EE)-induced cholestasis in the rat.
Main Methods: CBS (50 and 150 mg/kg per day) was intragastrically (i. g.) given to experimental rats for 5 consecutive days in coadministration with EE. The levels of serum biomarkers, hepatic malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were determined by biochemical methods. The bile flow in 2h was measured. The histopathology of the liver tissue was evaluated. The expression of transporter was studied by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and western blot.
Key Findings: CBS treatment significantly prevented EE-induced increases in serum levels of biomarkers. Decreased bile flow by EE was restored with CBS treatment. The tissue lesions were also relieved with CBS treatment. Western blot studies indicated that EE significantly decreased the protein expression of multidrug resistance-associated protein 2 (Mrp2) and breast cancer resistance protein (Bcrp), but notably increased P-glycoprotein (P-gp) protein, compared with the control group. CBS treatment significantly increased the protein expression of P-gp, Mrp2 and Bcrp compared with the EE group. RT-qPCR studies indicated that EE down-regulated Bcrp at transcriptional level. CBS up-regulated the mRNA expression of P-gp, Mrp2 and Bcrp compared with the EE group.
Significance: The present study indicated that CBS exerted a beneficial effect on EE-induced cholestasis in the rat, which may result from its induction of P-gp, Mrp2 and Bcrp expression.
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