As a serious complication of diabetes, nonhealing
skin ulcer leads to high mortality and disability in diabetic patients. However, limited
therapy is available in managing diabetic
wounds. In this study,
RNA-seq technology was used to systematically investigate the effect of
Huangbai (HB) liniment, a
traditional Chinese medicine, on the
streptozotocin- (STZ-) induced diabetic
wound. HB liniment significantly accelerated the
wound closure and enhanced the generation of extracellular matrix in diabetic rats, and oxidative stress was identified to play a vital role in HB-mediated wound healing. Importantly, HB liniment activated nuclear factor erythroid-derived 2-like 2 (Nrf2) and its downstream
antioxidant genes (e.g., genes involved in
glutathione system,
thioredoxin system, and GAPDH generation as well as other
antioxidant genes), which inhibited oxidative damage and apoptosis. By associating
drug targets of HB liniment with Nrf2 and its downstream genes, 54 components in HB liniment were screened out, and the majority was from Cortex Phellodendri and Forsythia suspensa. Additionally, HB liniment enhanced TGF-β1 and reduced MMP9 level, accelerating wound healing in diabetes. The in vitro experiment showed HB facilitated cell proliferation and inhibited oxidative damage in high
glucose-induced HaCaT cells. Our findings provided the experimental evidence for the treatment of diabetic
wound with HB, clarified the potential mechanism of HB, and improved our understanding of diabetic wound healing.