<i>Dendrobium officinale</i> Polysaccharide Promotes Infected Wound Healing Through SIRT1-Regulated HMGB1-K29 Deacetylation and NF-κB Inhibition

Abstract

Background: Two major challenges frequently encountered during wound healing are excessive inflammatory responses and bacterial infection. Dendrobium officinale polysaccharide (DOP), a major bioactive constituent of Dendrobium officinale, has shown potential for promoting infected wound healing and tissue repair. Objectives: This study evaluated the therapeutic efficacy of DOP in an infected murine wound model, with a specific focus on the role of the SIRT1/HMGB1/NF-κB signaling axis. Methods: Mouse full-thickness skin defect models were established, and animals were divided into four cohorts: control, infected model, DOP-treated, and DOP plus the SIRT1-specific inhibitor EX527. All groups except the control group were inoculated with Staphylococcus aureus. The primary endpoint was wound closure, quantified as the remaining wound surface area on day 14. Secondary outcomes included body weight changes, histopathological injury scores, inflammatory cytokine protein secretion and mRNA transcript levels, SIRT1 expression, HMGB1 subcellular localization, IκBα degradation, and NF-κB p65 phosphorylation. Results: For the primary endpoint, animals receiving DOP had markedly smaller unclosed wound areas on postoperative day 14 than untreated infected animals. Secondary analyses showed that DOP improved body weight recovery and reduced inflammatory cytokine secretion and corresponding mRNA transcript levels. Mechanistically, DOP increased SIRT1 protein levels, promoted HMGB1 deacetylation at the K29 residue with consequent nuclear sequestration, and suppressed IκBα proteolysis and NF-κB p65 phosphorylation. These protective effects were reversed by the SIRT1 inhibitor EX527. Conclusions: By activating SIRT1, DOP promotes K29 deacetylation of HMGB1 and retains this alarmin in the nucleus. The resulting suppression of NF-κB reduces inflammatory injury and counteracts the adverse effects of bacterial infection on wound repair. These findings provide an experimental basis for the potential application of DOP in the management of infected wounds.