Notoginsenoside R1 Facilitated Wound Healing in High-Fat Diet/Streptozotocin-Induced Diabetic Rats

Abstract

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.

Wound Healing Potential of Plant Secondary Metabolites: <em>In Silico</em>, <em>In Vitro,</em> and <em>In Vivo</em> Experiments

“…An interaction of AA with MMP-2 better than their natural inhibitor was also demonstrated in an in-silico study [32]. Other natural compounds such as quercetin, luteolin, vicenin-2, and notoginsenoside R1 have been associated with the downregulation of MMP-9, TNFα, IL1β, and IL6, and upregulation of antioxidant enzymes, TIMP, IL10, VEGF, TGFb1, on streptozotocin-induced diabetic rats [33][34][35]. For MMP-13 (which have essential roles in the turnover of the collagen matrix of bone) natural compounds such as curcumin, resveratrol, and epigallocatechin-3-gallate inhibit the IL-1β or advanced glycation end products-induced production of MMP-13, IL6 or TNFα by chondrocytes [36,37].…”

Targeting matrix metalloproteases in diabetic wound healing

“…More importantly, NR1 administration gives rise to the down-regulation of MMP-9, MMP-3, IL-1b, and IL-6, while up-regulation of TIMP1 as well as TGF-b1. The results of RNA-Seq technology illustrate that NR1 mainly influence ECM related processes and inflammation in diabetic wound healing by targeting TIMP-1 and MMP-3 (93). Thus, these phenomena indicate that NR1 may be a feasible candidate agent for diabetic ulcer via regulating MMP-mediated signaling pathway.…”

Pien-Tze-Huang alleviates CCl4-induced liver fibrosis through the inhibition of HSC autophagy and the TGF-β1/Smad2 pathway

“…In recent times, a variety of active compounds have been isolated and identified from PZH increasingly (Li et al, 2022b). Recently reported compounds are notoginsenoside (Cao et al, 2022), ginsenosides (Ramli et al, 2022), taurine (McGurk et al, 2022, citric acid and malic acid (Słupski et al, 2022), muscone (Fu et al, 2016) etc., which have been demonstrated to exhibit antioxidant, antiinflammatory, and anti-tumor effects (Huang et al, 2019). It has been reported that PZH perhaps heals a wide range of liver injuries and inflammation (Fu et al, 2016;Qi et al, 2017;Li et al, 2018;Zhang et al, 2018).…”