College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 610000, PR China; Department of Pharmacy, The Fifth Medical Center of PLA General Hospital, Beijing, 100039, PR China.
School of Food and Bioengineering, Xihua University, Chengdu 610039, PR China.
Eur J Pharmacol. 2022 Nov 15;935:175331. doi: 10.1016/j.ejphar.2022.175331. Epub 2022 Oct 21.
Numerous studies have clarified the effectiveness of paeoniflorin in the treatment of cholestasis. However, the therapeutic efficacy and mechanisms of action of paeoniflorin in intrahepatic cholestasis of pregnancy (ICP) were still unknown. This study aimed to investigate the molecular biological mechanisms of paeoniflorin against ICP by combining network pharmacology and metabolomics. The effects of paeoniflorin were investigated in the ICP rat model induced by 17α-ethinylestradiol, showing improvements in the liver indices, liver histopathological changes, bile flow rate, and serum levels of TBA and ALP. The underlying mechanisms and metabolic pathways of paeoniflorin were revealed by network pharmacology and untargeted metabolomics, showing that paeoniflorin exerted its curative effect against ICP-induced ferroptosis through PI3K/AKT and MAPK signalling pathways. In conclusion, paeoniflorin protected against ICP-induced liver injury through MAPK signaling pathways.
大量研究阐明了芍药苷在胆汁淤积治疗中的有效性。然而，芍药苷治疗妊娠肝内胆汁淤积症（ICP）的疗效和作用机制尚不清楚。本研究旨在通过网络药理学和代谢组学相结合，探讨芍药苷治疗 ICP 的分子生物学机制。在 17α-乙炔雌二醇诱导的 ICP 大鼠模型中研究了芍药苷的作用，结果显示肝指数、肝组织病理学变化、胆汁流速以及血清 TBA 和 ALP 水平得到改善。通过网络药理学和非靶向代谢组学揭示了芍药苷的作用机制和代谢途径，表明芍药苷通过 PI3K/AKT 和 MAPK 信号通路发挥对 ICP 诱导的铁死亡的治疗作用。总之，芍药苷通过 MAPK 信号通路对 ICP 诱导的肝损伤起保护作用。
