PF-PLC micelles ameliorate cholestatic liver injury via regulating TLR4/MyD88/NF-κB and PXR/CAR/UGT1A1 signaling pathways in EE-induced rats

Abstract

Paeoniflorin (PF) has a certain therapeutic effect on cholestasis liver injury. To further improve the bioavailability of PF and play its pharmacological role in liver protection, PF-phospholipid complex micelles (PF-PLC micelles) were prepared based on our previous research on PF-PLC. The protective effects of PF and PF-PLC micelles on cholestasis liver injury induced by 17α-ethynylestradiol (EE) were compared, and the possible mechanisms were further explored. Herein, we showed that PF-PLC micelles effectively improved liver function, alleviated liver pathological damage, and localized infiltration of inflammatory cells. Mechanism studies indicated that PF-PLC micelles treatment could suppress the TLR4/MyD88/NF-κB pathway, and further reduce the levels of pro-inflammatory factors. Meanwhile, our experimental results demonstrated that the beneficial effect of PF-PLC micelles on EE-induced cholestasis may be achieved by the upregulation of nuclear receptors and metabolic enzymes (PXR/CAR/UGT1A1). All these results indicate that PF-PLC micelles have great potential in the treatment of cholestatic liver disease.

Keywords: 17α-ethynylestradiol; CAR; Cholestasis liver injury; MyD88; NF-κB pathway; PF-PLC micelles; PXR; TLR4; UGT1A1.