San Huang decoction accelerates diabetic wound healing by restraining STING signaling to attenuate inflammation and enhance angiogenesis.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic foot, primarily caused by microvascular endothelial injury, is associated with a high risk of amputation due to the lack of effective drugs. San Huang Decoction (SHD), a traditional Chinese medicine formula, has been reported to have protective effects against diabetic cardiovascular complications. However, its potential role in promoting diabetic wound healing remains unclear.

AIM OF THE STUDY: This study aims to evaluate the effects and mechanisms of SHD in accelerating wound healing and to investigate its potential in restoring endothelial dysfunction under high-glucose conditions.

MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured under high-glucose conditions to assess the influence of SHD on endothelial dysfunction. A diabetic mouse model was established via high-fat diet feeding combined with streptozotocin (STZ) injection, followed by the creation of a full-thickness skin wound on the back. SHD extract was applied to evaluate its effects on wound healing. The chemical components of SHD were analyzed using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Additionally, network pharmacology and molecular docking were employed to identify active compounds and core target proteins.

RESULTS: SHD alleviated apoptosis and senescence of HUVECs induced by 40 mM glucose, while enhancing cell proliferation, migration, and tube formation. Mechanistic studies revealed that SHD inhibited the activation of the STING/TBK1 pathway in high-glucose-cultured endothelial cells, upregulated mRNA expression of PCNA, Ki67, and VEGF-A, and suppressed the expression of P21 and pro-inflammatory mediators. In vivo experiments showed that SHD promoted granulation tissue formation, collagen deposition, and angiogenesis. Network pharmacology and molecular docking indicated that palmatine chloride, sinensetin, and tangeretin are key components of SHD, interacting with STING, TBK1, and IRF3.

CONCLUSIONS: SHD may promote diabetic wound healing by inhibiting activation of the endothelial STING/TBK1-IRF3 signaling pathway. These findings provide a theoretical basis for further clinical investigation of SHD as a potential therapeutic agent for diabetic wound.