Natural Flavonoid-Derived Enzyme Mimics DHKNase Balance the Two-Edged Reactive Oxygen Species Function for Wound Healing and Inflammatory Bowel Disease Therapy
Guangfu Feng, Huaizu Zhang, Huipeng Liu, Xiaoyan Zhang, Hongmei Jiang, Sijie Liao, Xingyu Luo, Haowei Yao, Bo Xiang, Shiyu Liu, Jiali Zhang, Jiaheng Zhang, Jun Fang
Abstract
Rational regulation of reactive oxygen species (ROS) plays a vital importance in maintaining homeostasis of living biological systems. For ROS-related pathologies, chemotherapy technology derived from metal nanomaterials currently occupies a pivotal position. However, they suffer from inherent issues such as complicated synthesis, batch-to-batch variability, high cost, and potential biological toxicity caused by metal elements. Here, we reported for the first time that dual-action 3,5-dihydroxy-1-ketonaphthalene-structured small-molecule enzyme imitator (DHKNase) exhibited 2-edged ROS regulation, catering to the execution of physiology-beneficial ROS destiny among diverse pathologies in living systems. Based on this, DHKNase is validated to enable remarkable therapeutic effects in 2 classic disease models, including the pathogen-infected wound-healing model and the dextran sulfate sodium (DSS)-caused inflammatory bowel disease (IBD). This work provides a guiding landmark for developing novel natural small-molecule enzyme imitator and significantly expands their application potential in the biomedical field.