High-Throughput Screening of Natural Products Alleviating Diabetic Nephropathy Using a Peroxynitrite (ONOO ^– ) Responsive Fluorescent Probe

Peroxynitrite plays a key role in the progression of diabetic nephropathy (DN). Natural products, owing to their rich bioactivities, are frequently utilized in the discovery of candidate drugs. High-throughput screening based on monitoring peroxynitrite levels represents a promising strategy for identifying natural products. However, the inherent complexity and multipharmacology of natural products make it difficult to screen for traditional effective therapeutic drugs; thus, establishing robust high-throughput screening methodologies constitutes a critical objective to accelerate bioactive component discovery. Herein, we reported a sensitive probe (RNF) based on a peroxynitrite response and established a high-throughput screening platform to discover antioxidative protective agents. Through screening, astragalus polysaccharides (APS) were identified as potential natural antioxidants. The therapeutic mechanism has been demonstrated to activate the Nrf2/HO-1 signaling pathway, thereby inhibiting oxidative stress. This research developed a novel sensing strategy for the early detection of DN and provided an efficient platform for screening natural antioxidants.