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

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.