Pimpinella thellungiana ameliorates liver damage in osteoporotic rats based on metabolomics and network pharmacology

Background: Postmenopausal conditions can lead to metabolic disorders such as obesity and steatosis. Pimpinella thellungiana (PT), a prominent traditional Chinese medicine, exerts potential therapeutic effects against hepatic injury. Nevertheless, the extent to which PT ameliorates liver damage resulting from estrogen deficiency, along with the associated mechanisms, remains poorly understood. Purpose: This research aimed to investigate the hepatoprotective properties of PT in an ovariectomized (OVX) rat model. Methods: A bilateral ovariectomy was conducted to create an experimental model representative of liver injury induced by OVX. Serum biochemical analysis and a study of pathological changes were performed. Bone microstructure was detected using a micro-CT system. Liver metabolites were analyzed via LC-MS/MS. Network pharmacology was used to evaluate potential targets and pathways of metabolites related to PT intervention. Results: The findings indicated that the administration of PT resulted in a significant reduction in body weight, enhanced bone microarchitecture, and ameliorated liver tissue damage. Furthermore, PT treatment was able to notably modulate the levels of GGT and IL-6 while simultaneously elevating the concentrations of irisin and adiponectin and reducing the levels of insulin and leptin. Additionally, it contributed to the restoration of the metabolic profile of the liver in OVX rats. PT administration could mainly act on targets such as AKT1, BCL2 and FGF2, and associated pathways such as "insulin resistance" the "PPAR signaling pathway" and the "NF-kappa B signaling pathway", among others. PT administration improved glycerophospholipid metabolism. Conclusions: PT mitigated liver injury caused by estrogen deficiency in OVX rats. The potential mechanism may involve the regulation of insulin resistance and the signaling pathways associated with glycerophospholipid metabolism.