Dual-Functional Antioxidant CIRAKLC Peptide Discovery: A Biomaterial-Integrated Strategy for ROS Scavenging and Enzyme Modulation in Oxidative Stress Therapeutics

作者：Xin Liu, Han Wu, Zekai Ren, Yumei Wang, Ge Yang, Hailin Cong, Bing Yu · 发表于：ACS Applied Materials & Interfaces · 年份：2025 · DOI：10.1021/acsami.5c05089 · 被引用次数：6 · 研究领域：Biochemical effects in animals、Advanced Nanomaterials in Catalysis、Electrochemical sensors and biosensors

Antioxidants play a pivotal role in activating endogenous defense mechanisms, neutralizing free radicals, and mitigating oxidative stress. In this study, an antioxidant peptide library was constructed based on amino acid structure–activity relationships, focusing on ROS scavenging and enzymatic modulation. Through comprehensive chemical and biological evaluations, we identified the peptide CIRAKLC (designated as CL7), which exhibited exceptional ROS-scavenging capacity and enzyme-modulating activity, demonstrating superior in vitro antioxidant efficacy. CL7 exhibited excellent biocompatibility and effectively protected HepG2 cells from H 2 O 2 -induced ROS-mediated oxidative damage through both preventive and reparative mechanisms. Furthermore, CL7 modulated key enzymes (CAT, MDA, SOD, ALT, and AST), displaying hepatoprotective, anti-inflammatory, and antiaging effects, along with significant photoprotective efficacy. Molecular docking revealed key hydrogen bonding and electrostatic interactions when the peptide binds to redox-related receptors (Nrf2/Keap1 and IKK-β). These findings underscore CL7’s robust antioxidant capacity and multifunctionality, highlighting its broad therapeutic potential in oxidative stress management.