Effect of andrographolide on wound healing in diabetes rats by regulating the Wnt/β-catenin signaling pathway

DONG Guodong; CUI Zhaowei; ZHAO Yang

doi:10.3969/j.issn.1002-7386.2025.12.013

Abstract：Objective To investigate the impacts of andrographolide on wound healing in diabetes rats by regulating the Wnt/β-catenin signaling pathway.Methods A total of 60 Sprague-Dawley(SD)rats were randomly separated into diabetes foot group,normal group,andrographolide group,Wnt/β-catenin pathway inhibitor(DKK-1)group,and andrographolide+DKK-1 group,with 12 rats in each group.In addition to the normal group,rats in other groups were fed with high-glucose and high-fat diet,injected with streptozotocin and punched with a hole maker to create a foot wound to create the diabetes foot model.After successful modeling,once daily administration was given for 4 weeks.The changes in wound healing rate,fasting insulin,and fasting blood glucose in rats were detected.The hematoxylin and eosin(H&E)staining was applied to detect pathological changes in wound tissue.The enzyme-linked immunosorbent assay(ELISA)was applied to detect levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and IL-10 in wound tissue.Immunohistochemistry was applied to detect the average optical density values of vascular endothelial growth factor(VEGF)and platelet endothelial cell adhesion molecule(CD31)in wound tissue.Western blot was applied to detect protein levels of Wnt3a and β-catenin in wound tissue.Results Compared with those in the normal group,rats in the diabetes foot group had significantly thickened epithelium of the wound,massive inflammatory cell infiltration,lower wound healing rate,relative level of IL-10 in wound tissue,average optical densities of VEGF and CD31,and protein levels of Wnt3a and β-catenin,but higher fasting insulin,fasting blood glucose and relative levels of TNF-α and IL-6 in wound tissue(P＜0.05).Compared with the diabetes foot group,rats in the andrographolide group had significantly thickened epithelium of the wound,reduced inflammatory cell infiltration,higher wound healing rate,relative level of IL-10 in wound tissue,average optical densities of VEGF and CD31,and protein levels of Wnt3a and β-catenin,but lower fasting insulin,fasting blood glucose and relative levels of TNF-α and IL-6 in wound tissue(P＜0.05).Opposite findings were detected in the DKK-1 group(P＜0.05).DKK-1 weakened the effect of andrographolide on promoting wound healing in rats with diabetes foot.Conclusion Andrographolide promotes wound healing in rats with diabetes foot by activating the Wnt/β-catenin pathway.