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Wound Healing Effects of Dracontomelon dao on Bacterial Infection Wounds in Rats and Its Potential Mechanisms under Simulated Space Environment.

ABSTRACT: Dracontomelon dao (D. dao) is the leaves of Dracontomelon duperreanum Pierre (D. dao auct. non (Blanco) Merr. and Rolfe; D. sinense Stopf.). As a valuable traditional Chinese medicine from Anacardiaceae, D. dao has a long history of treating bedsores, skin ulcers, and other infection diseases. In addition, the volatile oil from D. dao leaves exhibits antitumor effects. However, these reported studies only focused on evaluating the antimicrobial efficacy on model strains in vitro, without paying attention to the antimicrobial activity and anti-inflammatory effects in vivo. This study was aimed to provide evidence of antimicrobial activity and anti-inflammatory and proangiogenesis activities of Dracontomelon dao (D. dao) on the skin of rats under simulated space environment. The weightlessness model of rats in space environment was established. Then, rats were given D. dao for 15 days. Wound healing effects of D. dao on histopathology and inflammatory cytokines in E. coli-induced wound infection in weightless rats were analyzed. Furthermore, the molecular biology technology was performed to evaluate the wound healing effects of D. dao on the relative protein level of NF-κB as well as PI3K/Akt signaling pathways. Immunohistochemistry was used for the protein expression of VEGFA. The wound healing effects of D. dao on bacterially infected wounds in rats were manifested by lowering the size of the wound and significantly increasing the shrinkage rate of the wound. D. dao had effect on alleviating histological damage of skin tissue and downregulation inflammatory cytokines level. In addition, the results indicated that D. dao has a regulatory effect on inflammation and angiogenesis and could regulate the relative protein level of MAPK/NF-κB as well as PI3K/AKT signaling pathways. The current study highlighted the crucial role of D. dao in relieving skin tissue injury in E. coli-induced wound infection in weightless rats by regulating the MAPK/NF-κB as well as PI3K/AKT signaling pathways. This study could provide a new agent for the treatment of bacterial infected wounds in simulated space environment.

SUBMITTER: Wen J

PROVIDER: S-EPMC9249481 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundWe recently reported the clinical safety profile of RJX, a well-defined intravenous GMP-grade pharmaceutical formulation of anti-oxidant and anti-inflammatory vitamins as active ingredients, in a Phase 1 study in healthy volunteers (ClinicalTrials.gov Identifier: NCT03680105) (Uckun et al., Front. Pharmacol. 11, 594321. 10.3389/fphar.2020.594321). The primary objective of the present study was to examine the effects of GMP-grade RJX on wound and burn injury healing in diabetic rats.MethodsIn the present study, a rat model of T2DM was used that employs HFD in combination with a single injection of STZ intraperitoneally (i.p) at a moderate dose level (45 mg/kg). Anesthetized diabetic rats underwent full-thickness skin excision on the back or were subjected to burn injury via a heated brass probe and then started on treatments with normal saline (NS = vehicle) or RJX administered via intraperitoneal injections for three weeks.FindingsNotably, diabetic rats treated with the 1.25 mL/kg or 2.5 mL/kg RJX (DM+RJX groups) rapidly healed their wounds as fast as non-diabetic control rats. Inflammatory cell infiltration in the dermis along with fibrin and cell debris on the epithelial layer persisted for up to 14 days in the DM+NS group but not in RJX-treated groups. The histopathological score of wound healing on days 7 and 14 was better in diabetic rats treated with RJX than diabetic rats treated with NS and comparable to the scores for non-diabetic healthy rats consistent with an accelerated healing process. The residual wound area of RJX-treated rats was significantly smaller than that of NS-treated diabetic rats at each evaluation time point (P<0.001). The accelerating effect of RJX on diabetic wound healing was dose-dependent. We obtained similar results in the burn injury model. Our results demonstrate that RJX - at a dose level >10-fold lower than its clinical maximum tolerated dose (MTD) - accelerates the healing of excision wounds as well burn injury in diabetic rats.

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Wound Healing Effects of Dracontomelon dao on Bacterial Infection Wounds in Rats and Its Potential Mechanisms under Simulated Space Environment.

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