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Huangbai Liniment Accelerated Wound Healing by Activating Nrf2 Signaling in Diabetes.

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-?1 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.

SUBMITTER: Zhang J

PROVIDER: S-EPMC7271242 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Huangbai Liniment Accelerated Wound Healing by Activating Nrf2 Signaling in Diabetes.

Zhang Jingjing J Zhou Rui R Xiang Changpei C Jia Qiang Q Wu Hongwei H Yang Hongjun H

Oxidative medicine and cellular longevity 20200523

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 dia ...[more]

PMID: 32566084

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Project description:Wound healing is strongly associated with the presence of a balanced content of reactive species in which oxygen-dependent, redox-sensitive signaling represents an essential step in the healing cascade. Numerous studies have demonstrated that cold physical plasma supports wound healing due to its ability to deliver a beneficial mixture of reactive species directly to the cells. Methods: We described a preclinical proof-of-principle-concept of cold plasma use in a dermal, full-thickness wound model in immunocompetent SKH1 mice. Quantitative PCR, Western blot analysis, immunohistochemistry and immunofluorescence were perfomed to evaluate the expression and cellular translocation of essential targets of Nrf2 and p53 signaling as well as immunomodulatory and angiogenetic factors. Apoptosis and proliferation were detected using TUNEL assay and Ki67 staining, respectively. Cytokine levels in serum were measured using bead-based multiplex cytokine analysis. Epidermal keratinocytes and dermal fibroblasts were isolated from mouse skin to perform functional knockdown experiments. Intravital fluorescence analysis was used to illustrate and quantified microvascular features. Results: Plasma exerted significant effects on wound healing in mice, including the promotion of granulation and reepithelialization as a consequence of the migration of skin cells, the balance of antioxidant and inflammatory response, and the early induction of macrophage and neutrophil recruitment to the wound sites. Moreover, through an early and local plasma-induced p53 inhibition with a concomitant stimulation of proliferation, the upregulation of angiogenetic factors, and an increased outgrowth of new vessels, our findings explain why dermal skin repair is accelerated. The cellular redox homeostasis was maintained and cells were defended from damage by a strong modulation of the nuclear E2-related factor (Nrf2) pathway and redox-sensitive p53 signaling. Conclusions: Although acute wound healing is non-problematic, the pathways highlighted that mainly the activation of Nrf2 signaling is a promising strategy for the clinical use of cold plasma in chronic wound healing.

Project description:Development of natural protein-based fibrous scaffolds with tunable physical properties and biocompatibility is highly desirable to construct three-dimensional (3D), fully cellularized scaffolds for wound healing. Herein, we demonstrated a simple and effective technique to construct electrospun 3D fibrous scaffolds for accelerated wound healing using a photocrosslinkable hydrogel based on gelatin methacryloyl (GelMA). We found that the physical properties of the photocrosslinkable hydrogel including water retention, stiffness, strength, elasticity and degradation can be tailored by changing the light exposure time. We further observed that the optimized hydrogel fibrous scaffolds which were soft and elastic could support cell adhesion, proliferation and migration into the whole scaffolds, facilitating regeneration and formation of cutaneous tissues within two weeks. Such tunable characteristics of the fibrous GelMA scaffolds distinguished them from other reported substrates developed for reconstruction of wound defects including glutaraldehyde-crosslinked gelatin or poly (lactic-co-glycolic acid) (PLGA), whose physical and chemical properties were difficult to modify to allow cell infiltration into the 3D scaffolds for tissue regeneration. We anticipate that the ability to become fully cellularized will make the engineered GelMA fibrous scaffolds suitable for widespread applications as skin substitutes or wound dressings.Statement of significanceIn present study, we generate three-dimensional photocrosslinkable gelatin (GelMA)-based fibrous scaffolds with tunable physical and biological properties by using a combined photocrosslinking/electrospinning approach. The developed GelMA fibrous scaffolds can not only support cell viability and cell adhesion, but also facilitate cell migration and proliferation, accelerating regeneration and formation of cutaneous tissues. In addition, the physical properties of the engineered fibrous GelMA hydrogel including water retention capability, mechanical properties and biodegradability can be tuned to accommodate different patients' needs, making it a promising candidate for skin tissue engineering.

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Huangbai Liniment Accelerated Wound Healing by Activating Nrf2 Signaling in Diabetes.

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Huangbai Liniment Accelerated Wound Healing by Activating Nrf2 Signaling in Diabetes.

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