Arundina graminifolia Ameliorates Cisplatin-Induced Acute Kidney Injury via Pathological Targeted Recruitment of Flavonoid Aglycones: A Study Integrating Serum/Kidney Pharmacochemistry and Network Pharmacology

Cisplatin-induced acute kidney injury (AKI) poses a significant clinical challenge lacking specific therapeutic drugs. Arundina graminifolia, a traditional Dai medicine, exhibits notable renoprotective effects; however, its in vivo pharmacodynamic material basis and molecular mechanisms remain unclear. This study aimed to explore its mechanisms against AKI from the perspective of authentic kidney-migrating components. A cisplatin-induced mouse AKI model was established to evaluate the renoprotective effects of the A. graminifolia extract (BYJ) via biochemical markers and histopathology. UPLC-Q-TOF-MS/MS was employed to comparatively analyze the blood and kidney-migrating components between normal and AKI mice. Network pharmacology and molecular docking were subsequently applied to predict and validate the core signaling pathways based on the specific components detected in the injured kidneys. Results showed that BYJ administration significantly ameliorated renal dysfunction, restored antioxidant capacity, and alleviated tubular necrosis. MS analysis identified 93 chemical components in vitro. In vivo tracking revealed a “pathological targeted recruitment” characteristic: only 6 prototype components entered normal kidneys, whereas 16 prototypes penetrated the AKI kidneys, highly enriched in lipophilic flavonoid aglycones such as kaempferol and apigenin. Network pharmacology predicted that these targeted components could potentially interact with 124 key targets (including AKT1, PIK3CA, and EGFR) to putatively exert anti-apoptotic and anti-inflammatory effects via the PI3K-Akt, TNF, and MAPK pathways. Molecular docking confirmed excellent binding affinities between these aglycones and core target proteins (e.g., kaempferol with PIK3CA at −8.9 kcal/mol). Based on actual in vivo distribution, this study reveals the specific accumulation of polyhydroxy flavonoid aglycones in injured kidneys, providing a reliable scientific basis for defining the pharmacodynamic substances of A. graminifolia.