Regenerative Effects of α-Mangostin-Loaded ZnO Nanoparticles on Wound Healing: In Vitro and Zebrafish In Vivo Insights

Abstract

α-Mangostin, a key bioactive compound derived from the peel of Garcinia mangostana, is known for its wound-healing potential. This study aims to evaluate the synergistic effects of α-Mangostin-derived zinc oxide nanoparticles (α-Mangostin–ZnO NPs) on wound healing, with emphasis on antimicrobial, anti-inflammatory, antioxidant, and molecular mechanisms. α-Mangostin–ZnO nanoparticles were assessed using in vitro antimicrobial assays against wound-associated pathogens (Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Vibrio vulnificus). Anti-inflammatory activity was evaluated by protein denaturation inhibition using ibuprofen as a reference, while antioxidant potential was assessed using the DPPH free radical scavenging assay. In silico molecular docking was performed against key target proteins (7S53, 4NG2, 20MF, and 5TV2). In vivo wound-healing efficacy was examined using a zebrafish wound model, along with RT-PCR analysis of inflammatory gene expression. α-Mangostin–ZnO NPs exhibited enhanced antimicrobial activity compared to individual components. Significant inhibition of protein denaturation and strong DPPH radical scavenging activity indicated potent anti-inflammatory and antioxidant effects. Molecular docking revealed strong binding affinities with antimicrobial, oxidative stress, inflammatory, and wound-healing proteins. RT-PCR analysis showed marked downregulation of pro-inflammatory markers (mmp13, TNF-α, and IL-1β). Zebrafish studies demonstrated accelerated wound closure and improved tissue regeneration. The findings demonstrate that α-Mangostin–ZnO NPs act as a multifunctional wound-healing agent by integrating antimicrobial, antioxidant, and anti-inflammatory actions, supported by molecular targeting. This nanoplatform shows strong potential for future wound-healing applications.