Dissection of the Potential Activity Materials and Mechanism of Cortex Moutan Based on In Vivo Substances Profiling

ABSTRACT This study aimed to identify the main chemical components of Moutan Cortex (MC) using Ultra‐High‐performance liquid chromatography and quadrupole time‐of‐flight (TOF) mass spectrometry and explore its therapeutic targets for hemorrhagic fever with renal syndrome complications through network pharmacology. A total of 28 compounds were identified in MC, including 7 gallic acylglucoses, 10 monoterpenoids, 6 paeonol compounds, 2 organic acids, and 3 flavonoids. In addition, after the rats ingested MC, six prototype substances were clearly identified in the rat plasma. Using VENNY and STRING databases, 161 intersection targets between MC and hemorrhagic fever with renal syndrome were identified, with key targets including VACM‐1, PIK3R1, PIK3CA, EGFR, MAPK1, TP53, and AKT1. These targets are involved in PI3K‐AKT and other signaling pathways, influencing cell survival, apoptosis, and inflammatory responses. Experimental validation showed that MC significantly reduced blood glucose, creatinine, and urea nitrogen levels in hemorrhagic fever with renal syndrome model rats and improved kidney function. Additionally, qRT‐PCR analysis demonstrated that high‐dose MC intervention effectively decreased the expression of VCAM‐1 and IL‐1β, both in serum and at the mRNA level in renal tissue, indicating its potent anti‐inflammatory effects. These findings suggest that MC exerts multifaceted therapeutic effects on HFRS through multicomponent, multitarget, and multipathway mechanisms, providing a theoretical basis for its clinical application.