7-hydroxycoumarin-β-D-glucuronide protects against cisplatin-induced acute kidney injury via inhibiting p38 MAPK-mediated apoptosis in mice

Cisplatin is a common chemotherapeutic agent limited by severe nephrotoxicity, which easily induces acute kidney injury (AKI) in tumor patients. 7-hydroxycoumarin-β-D-glucuronide (7-HCG), a major kidney-enriched metabolite of coumarins from Hydrangea paniculata, was previously found to accumulate specifically in renal tissue with long elimination half-life. In this study, male C57BL/6 mice were pretreated with 7-HCG at three doses, followed by intraperitoneal cisplatin injection to establish AKI model.

Renal tissue mRNA sequencing was performed on control, cisplatin model, 15 mg/kg and 30 mg/kg 7-HCG groups to explore transcriptomic changes. Transcriptome analysis revealed that 7-HCG reversed dysregulated MAPK signaling and apoptosis pathways triggered by cisplatin. Further validation confirmed that 7-HCG reduced renal ROS production, suppressed phosphorylation of p38/ERK/JNK, and downregulated pro-apoptotic proteins Bax and cleaved-caspase3.