Yinzhilan Formula Ameliorates Healing Delay in Diabetic Ulcer by Inhibiting PARP1 Activation and Regulating Macrophage Polarization

Introduction: Yinzhilan formula (YZL) is an effective prescription for diabetic ulcers (DU) with clinical efficacy. This study aimed to explore the mechanism of YZL in ameliorating the healing delay of DU through network pharmacology and experimental validation. Methods: Network pharmacology integrated with bioinformatics to screen the chemical composition of YZL, as well as its protein targets and disease targets. A mouse model of DU was established, and the efficacy of YZL was evaluated according to ulcer size and histopathological examination. The levels of inflammatory factors were detected by ELISA, and the changes in macrophage polarization were detected by immunofluorescence and flow cytometry. Results: Network pharmacology identified 291 potential targets in YZL, which synergistically targeted PARP1 and STAT3 to exert their role in promoting wound healing. In vivo experiments showed that YZL accelerated wound closure, regulated the levels of inflammatory factors and macrophage polarization, and suppressed the mRNA and protein expression levels of PARP1 and STAT3. Discussion: Bioinformatics studies suggested that HSP90AA1, IL6, PARP1, and STAT3 may be potential targets of YZL in the treatment of DU. Immune infiltration analysis suggested that macrophages may be related to the mechanism of action. Conclusion: YZL may accelerate DU healing by inhibiting PARP1 and STAT3 and reprogramming macrophage polarization towards the M2 phenotype.