Effects of Tiger Tail Sea Cucumber Bohadschia argus on Wound Healing In Vitro and In Vivo Using an Acute Rat Model Infected with Staphylococcus aureus

Abstract Infectious wounds caused by Staphylococcus aureus remain a significant clinical challenge due to delayed healing and increasing antimicrobial resistance, necessitating alternative therapeutic strategies. This study aimed to evaluate the wound-healing potential of the ethanol extract of the tiger tail sea cucumber Bohadschia argus (EEBA) through integrated in vitro, in vivo, and in silico approaches. Phytochemical profiling using LC-HRMS identified 260 metabolites, and 12 prioritized compounds were selected for molecular docking analysis. EEBA demonstrated concentration-dependent antioxidant activity in the nitric oxide scavenging assay and inhibitory effects on protein denaturation, indicating anti-inflammatory potential, although differences compared to controls were not statistically significant (p > 0.05). In an excisional wound model in Staphylococcus aureus-infected Wistar rats, topical application of 1% EEBA accelerated wound contraction and improved macroscopic healing compared to the negative control. Histopathological evaluation revealed reduced inflammatory cell infiltration, enhanced fibroblast proliferation, increased angiogenesis, and improved collagen organization across the inflammatory, proliferative, and maturation phases. Hemolysis testing confirmed good biocompatibility with negligible erythrocyte lysis (<5%). Molecular docking demonstrated favorable binding affinities of selected compounds toward key inflammatory targets, including TNF-α, NF-κB, and FLAP, as well as antibacterial targets relevant to Staphylococcus aureus, namely, DNA gyrase-B, dihydrofolate reductase, and penicillin-binding protein. These findings provide preliminary mechanistic insights into the potential wound-healing and antibacterial activities of EEBA. Overall, EEBA exhibits promising wound-healing activity in an infected wound model through modulation of oxidative stress and inflammatory pathways, with selected metabolites also showing potential interactions with bacterial targets associated with S. aureus infection. These findings support the potential development of EEBA as a natural therapeutic candidate for infected wound management.