Identification of a Benzoquinone Antimicrobial from Ilicis Rotundae Cortex and Its Microneedle-Based Delivery for Infected Wound Healing

Abstract

Wound infections caused by fungi and bacteria remain a major global health challenge. In this study, 2,6-dimethoxy-1,4-benzoquinone (DMBQ) was isolated from Ilicis Rotundae Cortex (IRC). The compound yields inhibitory effects on Candida albicans (C. albicans), Staphylococcus aureus (S. aureus), and Escherichia coli (E. coli). Specifically, DMBQ disrupts the cell membrane structure of fungi and bacteria, alters membrane permeability, and induces intracellular reactive oxygen species (ROS) accumulation. In addition, DMBQ effectively suppresses the biosynthesis of fungal ergosterol and bacterial fatty acids. The synergistic action of these multiple mechanisms contributes to the antimicrobial effects of DMBQ. We further fabricated DMBQ-loaded photocurable hydrogel microneedles, HA-GMA-DMBQ MNs (HGD MNs). The covalently cross-linked network of HGD MNs boosts mechanical strength, allowing efficient stratum corneum penetration. HGD MNs exert certain in vitro antimicrobial activity, regulate the wound inflammatory microenvironment in vivo, promote CD31-mediated angiogenesis, and accelerate infected wound healing. Collectively, this work identifies DMBQ as a natural antimicrobial agent, and its combination with hydrogel microneedles offers an effective route for swift therapy of infected wounds.