Shengji ointment accelerates diabetic foot ulcer wound healing by regulating inflammatory microenvironment

Background Diabetic foot ulcers (DFUs) represent a significant clinical challenge due to their high morbidity, infection risk, and poor healing rates. Emerging evidence highlights the therapeutic potential of Traditional Chinese Medicine in wound management. This study investigates the efficacy of Shengji Ointment (SJ)—a multi-herb formulation—in human subjects with DFUs and a diabetic rat model, specifically elucidating its modulation of the wound inflammatory microenvironment. Methods The lyophilized powder of the SJ extract was analyzed using UPLC-MS/MS to profile its chemical constituents. A single-center, prospective, randomized, controlled clinical study was conducted in patients with Wagner Grade 3 DFUs. A diabetic wound rat model was established, and proinflammatory cytokine and growth factor levels in granulation tissue were quantified at multiple time points. Results UPLC-MS/MS identified 3,552 distinct UPLC-MS/MS identified 3,552 distinct compounds in the SJ extract, predominantly flavonoids and alkaloids in the SJ extract, predominantly flavonoids and alkaloids; 10 high-abundance compounds were selected (5 at MSI Level 1). The clinical study demonstrated that SJ significantly accelerated DFU wound healing. The animal study revealed that SJ promotes wound healing by modulating the wound microenvironment. Conclusions This study demonstrated that Shengji Ointment (SJ) could inhibit excessive inflammation, promote angiogenesis and vascular maturation, and thereby markedly accelerate diabetic wound healing in both clinical settings and rat models. Such therapeutic effects may be associated with the DLL4/Notch1-VEGF/VEGFR2 signaling pathway.