Abstract Oxidative stress is a central pathological driver in diabetic nephropathy (DN), leading to excessive reactive oxygen species (ROS) generation, chronic inflammation, and progressive renal fibrosis. Effective modulation of oxidative imbalance thus represents a vital therapeutic strategy for mitigating DN progression. Here, we developed a bioinspired polyphenolic nanoplatform by first constructing polymerized grape seed polyphenol nanoparticles via enzymatic polymerization, followed by supramolecular assembly with the bioactive polyphenol resveratrol. This design combined the intrinsic bioactivity of polyphenols with active resveratrol integration, yielding a stable and biocompatible strategy that alleviated DN and enabled superior restoration of renal structure and function. In diabetic models, it promoted coordinated recovery of renal morphology, key structural proteins, and physiological function, suggesting potential advantages for long-term renal protection beyond short-term biochemical improvement. These findings demonstrated that enzymatically engineered polyphenolic nanotherapeutics provided a potent and biocompatible approach for oxidative regulation and functional renal restoration in DN therapy.
Cai et al. (Sun,) studied this question.
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