Engineered Carbon Dots from a Traditional Herb Pair Orchestrate Concurrent Antioxidant and AP‐1‐Mediated Inflammation to Attenuate Renal Ischemia‐Reperfusion Injury

ABSTRACT Renal ischemia‐reperfusion (I/R) injury, a primary cause of acute kidney injury (AKI), is driven by a self‐amplifying loop of oxidative burst and immune cell infiltration. In this work, the classical herb pair Astragalus membranaceus (AM) and Angelica sinensis (AS) is employed as a composite precursor to synthesize nitrogen‐rich carbon‐dot nanozymes (AM‐AS@CDs) via a one‐step hydrothermal method. AM‑AS@CDs exhibit superoxide dismutase (SOD)‐mimetic activity superior to that of CDs derived from single herbs. In vitro, AM‐AS@CDs effectively alleviate oxidative stress‐induced cellular damage and significantly inhibit apoptosis. In vivo, AM‐AS@CDs markedly attenuate I/R‐induced AKI and reduce immune cell infiltration in renal tissues. Transcriptomic analyses reveal that AM‐AS@CDs downregulate the expression and phosphorylation of Fosl1 and c‐Jun. Consequently, the AP‐1‐chemokine signaling axis is disrupted, which reduces immune cell recruitment. Furthermore, AM‐AS@CDs restore redox homeostasis by upregulating antioxidant enzymes such as SOD, glutathione peroxidase 4 (GPX4), and catalase (CAT). They also attenuate the excessive activation of the Nrf2/HO‐1 pathway. Overall, this precursor‐formulation strategy enables precise modulation of heteroatom doping and surface chemistry in CDs. AM‐AS@CDs effectively interrupt the oxidative‐inflammatory positive feedback loop through dual mechanisms. These findings provide both theoretical and material foundations for the development of natural product‐based nanozymes for I/R‐related diseases.