The high disability, mortality and morbidity of diabetic ulcers indicate the urgent need to explore effective strategies for diabetic wound repair. TrxR1 plays a vital role in regulating redox homeostasis in various pathologies. In this study, the effect of berberine (BBR) on diabetic wounds was investigated by utilizing streptozotocin (STZ)-induced diabetic rats and a high glucose-induced cell model, and the mechanism of BBR on TrxR1 was elucidated. BBR treatment remarkably accelerated wound healing and enhanced extracellular matrix synthesis and significantly inhibited high glucose-induced HaCaT cell damage. Further analysis indicated that BBR activated TrxR1, suppressed its downstream JNK signaling, thereby inhibiting oxidative stress and apoptosis, promoted cell proliferation, downregulated MMP9 and upregulated TGF-β1 and TIMP1, resulting in accelerated wound healing. Importantly, the enhancement of BBR on wound repair was further abolished by TrxR1 inhibitor. Moreover, in diabetic wounds induced by a combination of STZ injection and high fat diet, BBR significantly increased wound closure rate and TrxR1 expression, and this was reversed by TrxR1 inhibitor. These data indicated that topical BBR treatment accelerated diabetic wound healing by activating TrxR1. Targeting TrxR1 may be a novel, effective strategy for restoring redox homeostasis and promoting diabetic wound healing.

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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.

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C5ar1 (CD88) has been identified as an important potential therapeutic target for regulating inflammation in ischemic stroke. In this study, the neuroprotective effect of Guhong injection (GHI) on middle cerebral artery occlusion (MCAO)-induced reperfusion injury was assessed and the mechanism was explored by RNA-seq technology. GHI administered for 6 consecutive days significantly decreased body weight loss, infarction rate, neurological deficient scores, and neuron loss but improved rat survival percentage and regional cerebral blood flow after MCAO surgery. Furthermore, we identified inflammation as a vital process and C5AR1 as a vital target in GHI-mediated protection by using RNA-seq analysis. Further experiments confirmed that GHI decreased C5AR1, C5A, CASP3, 8-OHdG, and inflammatory factors such as IL-1β, TNF, IL6, ICAM-1, MMP9, and MCP-1, and enhanced the expression of TIMP1, JAM-A, and laminin. Furthermore, GHI and its major components hydroxysafflower yellow A (HSYA) and aceglutamide (AG) enhanced cell viability and reduced LDH level and C5AR1 expression in a C5A-induced Neuro-2a cell damage model. In general, this study elucidated the mechanism of GHI against ischemic stroke by inhibiting inflammation and highlighted the potential important role of C5AR1 in ischemic stroke. This research provided new insights into the mechanism of GHI in resisting ischemic stroke and benefits of its clinical application.