Abstract
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.
Highlights
Chronic nonhealing wound is a serious diabetic complication, which leads to severe morbidity and mortality in diabetic population and brings a huge social and economic burden to the word [1, 2]
HB liniment and rhEGF treated rats demonstrated a stronger staining than that of the STZ group as indicated by hematoxylin and eosin (HE) staining and Masson staining (Figure 1(d)), indicating improved extracellular matrix (ECM) synthesis and collagen production by HB and rhEGF treatments. These results demonstrated that HB treatment promoted wound healing in STZ-induced diabetic rats
The activation of nuclear factor erythroid-derived 2-like 2 (Nrf2) and its downstream genes involved in glutathione system, thioredoxin system, and NADPH generation as well as other antioxidant genes were observed after HB treatment
Summary
Chronic nonhealing wound is a serious diabetic complication, which leads to severe morbidity and mortality in diabetic population and brings a huge social and economic burden to the word [1, 2]. In contrast to the typical sequential emergence of biological process of coagulation, inflammation, proliferation, and remodeling in normal tissue, the normal progression of wound healing is disturbed and delayed in diabetes, resulting in long-term of wound nonunion [3, 4]. Conventional therapies are only effective in the management of diabetic wounds to certain degree, whereas a large number of diabetic wounds still persist, deteriorate, and result in amputation [5]. A reduced efficiency in diabetic wound healing is usually accompanied with decreased blood supply, delayed extracellular matrix turnover, reduced wound contraction, repeated infections, and chronic inflammation, which hinders wound healing [4, 6]. It is urgent to develop an effective therapy to treat diabetic wounds
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
