Diabetic
ulcers bring about high morbidity and mortality in patients and cause a great economic burden to society as a whole. Since existing treatments cannot fulfil patient requirements, it is urgent to find effective
therapies. In this study, the wound healing effect of topical
notoginsenoside R1 (NR1) treatment on diabetic full-thickness
wounds in type II
diabetes mellitus (T2DM) was induced by the combination of a high-fat diet and
streptozotocin (STZ) injection. NR1 significantly increased the
wound closure rate, enhanced extracellular matrix (ECM) secretion, promoted
collagen growth, increased
platelet endothelial cell adhesion molecule-1 (CD31) expression, and decreased cleaved
caspase-3 expression.
RNA-Seq analysis identified ECM remodeling and
inflammation as critical biological processes and Timp1 and Mmp3 as important targets in NR1-mediated wound healing. Further experiments showed that NR1-treated
wounds demonstrated higher expression of
tissue inhibitor of metalloproteinase 1 (TIMP1) and transforming growth factor-β1 (TGFβ1) and lower expression of matrix
metallopeptidase 9 (MMP9), matrix
metallopeptidase 3 (MMP3), interleukin-1β (IL-1β), and
interleukin-6 (IL-6) than diabetic
wounds. These investigations promote the understanding of the mechanism of NR1-mediated diabetic wound healing and provide a promising therapeutic
drug to enhance diabetic wound healing.