Therapeutic effects of Glycyrrhiza glabra aqueous extract ointment on cutaneous wound healing in Sprague Dawley male rats

Diet-induced overweight rats exhibit delayed cutaneous healing; however, when receiving an obesogenic diet, some rats are susceptible to developing the overweight phenotype, whereas others are resistant. We investigated cutaneous healing in diet-induced obesity (DIO)-prone and diet-resistant (DR) rats. Male rats were fed with a standard (control) or a high-saturated fat (30 % fat, w/w) diet for 20 weeks. Then, the experimental group was subdivided into DIO (n 17) and DR (n 16) groups. An excision lesion was made, and the animals were killed 7 or 14 d later. The average body weight was 29 and 25 % higher in the DIO group compared with the C and DR groups. Retroperitoneal fat was higher in the DIO group than in the control and DR groups (518 and 92 %) and was higher in the DR group than in the control group (223 %). The DIO group presented glucose intolerance, and both the DIO and DR groups presented delayed wound contraction (50 %) and re-epithelialisation (20 %). Compared with the DR group, the DIO group displayed higher amounts of inflammatory cells as well as higher levels of lipid peroxidation (P < 0·05). Myofibroblastic differentiation and vessel remodelling were delayed in both the DIO and DR groups. Nitrite levels were lower in the DIO group (340 % less) than in the DR group. TNF-α expression was increased in the DIO group (130 %) compared with the DR group. Our results showed that DIO as well as DR rats present delays in cutaneous wound healing, even though the DR group does not have an overweight phenotype.

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RNAseq Analysis of Treatment-dependent Signaling Changes During Inflammation in a Mouse Cutaneous Wound Healing Model.

10.21203/rs.3.rs-429791/v1 ◽

2021 ◽

Author(s):

III Georges St. Laurent ◽

Ian Toma ◽

Bernd Seilheimer ◽

Konstantin Cesnulevicius ◽

Myron Schultz ◽

...

Keyword(s):

Wound Healing ◽

Placebo Control ◽

Therapeutic Effects ◽

Mrna Levels ◽

Cutaneous Wound Healing ◽

Cutaneous Wound ◽

Synthetic Pathway ◽

Cox Inhibitor ◽

Wound Healing Model ◽

Healing Model

Abstract Background: Despite proven therapeutic effects in inflammatory conditions, the specific mechanisms of phytochemical therapies are not well understood. The transcriptome effects of Tr14 (Traumeel), a multicomponent natural product, and diclofenac, a non-selective cyclooxygenase (COX) inhibitor, were compared in a mouse cutaneous wound healing model to identify both known and novel pathways for the anti-inflammatory effect of plant-derived natural products. Methods: Skin samples from abraded mice were analyzed by single-molecule, amplification-free RNAseq transcript profiling at 7 points between 12-192 hours after injury. Immediately after injury, the wounds were treated with either diclofenac, Tr14, or placebo control (n=7 per group/time). RNAseq levels were compared between treatment and control at each time point using a systems biology approach. Results: At early time points (12-36 hours), both control and Tr14-treated wounds showed marked increase in the inducible COX2 enzyme mRNA, while diclofenac-treated wounds did not. Tr14, in contrast, modulated lipoxygenase transcripts, especially ALOX12/15, and phospholipases involved in arachidonate metabolism. Notably, Tr14 modulated a group of cell-type specific markers, including the T cell receptor, that could be explained by an overarching effect on the type of cells that were recruited into the wound tissue. Conclusions: Tr14 and diclofenac had very different effects on the COX/LOX synthetic pathway after cutaneous wounding. Tr14 allowed normal autoinduction of COX2 mRNA, but suppressed mRNA levels for key enzymes in the leukotriene synthetic pathway. Tr14 appeared to have a broad ‘phytocellular’ effect on the wound transcriptome by altering the balance of cell types present in the wound.

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Apoptotic bodies derived from mesenchymal stem cells promote cutaneous wound healing via regulating the functions of macrophages

Stem Cell Research & Therapy ◽

10.1186/s13287-020-02014-w ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Jin Liu ◽

Xinyu Qiu ◽

Yajie Lv ◽

Chenxi Zheng ◽

Yan Dong ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Mesenchymal Stem Cells ◽

Mouse Skin ◽

Skin Wound ◽

Therapeutic Effects ◽

Cutaneous Wound Healing ◽

Apoptotic Bodies ◽

Skin Wound Healing ◽

Cutaneous Wound

Abstract Background As the major interface between the body and the external environment, the skin is liable to various injuries. Skin injuries often lead to severe disability, and the exploration of promising therapeutic strategies is of great importance. Exogenous mesenchymal stem cell (MSC)-based therapy is a potential strategy due to the apparent therapeutic effects, while the underlying mechanism is still elusive. Interestingly, we observed the extensive apoptosis of exogenous bone marrow mesenchymal stem cells (BMMSCs) in a short time after transplantation in mouse skin wound healing models. Considering the roles of extracellular vesicles (EVs) in intercellular communication, we hypothesized that the numerous apoptotic bodies (ABs) released during apoptosis may partially contribute to the therapeutic effects. Methods ABs derived from MSCs were extracted, characterized, and applied in mouse skin wound healing models, and the therapeutic effects were evaluated. Then, the target cells of ABs were explored, and the effects of ABs on macrophages were investigated in vitro. Results We found ABs derived from MSCs promoted cutaneous wound healing via triggering the polarization of macrophages towards M2 phenotype. In addition, the functional converted macrophages further enhanced the migration and proliferation abilities of fibroblasts, which together facilitated the wound healing process. Conclusions Collectively, our study demonstrated that transplanted MSCs promoted cutaneous wound healing partially through releasing apoptotic bodies which could convert the macrophages towards an anti-inflammatory phenotype that plays a crucial role in the tissue repair process.

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MSC-Derived Exosome Promotes M2 Polarization and Enhances Cutaneous Wound Healing

Stem Cells International ◽

10.1155/2019/7132708 ◽

2019 ◽

Vol 2019 ◽

pp. 1-16 ◽

Cited By ~ 20

Author(s):

Xiaoning He ◽

Zhiwei Dong ◽

Yina Cao ◽

Han Wang ◽

Shiyu Liu ◽

...

Keyword(s):

Bone Marrow ◽

Wound Healing ◽

Wound Repair ◽

Macrophage Polarization ◽

Therapeutic Effects ◽

Cutaneous Wound Healing ◽

Bone Marrow Mscs ◽

Wound Site ◽

Cutaneous Wound ◽

M2 Polarization

Mesenchymal stem cell transplantation (MSCT) promotes cutaneous wound healing. Numerous studies have shown that the therapeutic effects of MSCT appear to be mediated by paracrine signaling. However, the cell-cell interaction during MSCT between MSCs and macrophages in the region of cutaneous wound healing is still unknown. In this study, early depletion of macrophages delayed the wound repair with MSC injection, which suggested that MSC-mediated wound healing required macrophages. Moreover, we demonstrated that systemically infused bone marrow MSCs (BMMSCs) and jaw bone marrow MSCs (JMMSCs) could translocate to the wound site, promote macrophages toward M2 polarization, and enhance wound healing.In vitrococulture of MSCs with macrophages enhanced their M2 polarization. Mechanistically, we found that exosomes derived from MSCs induced macrophage polarization and depletion of exosomes of MSCs reduced the M2 phenotype of macrophages. Infusing MSCs without exosomes led to lower number of M2 macrophages at the wound site along with delayed wound repair. We further showed that the miR-223, derived from exosomes of MSCs, regulated macrophage polarization by targeting pknox1. These findings provided the evidence that MSCT elicits M2 polarization of macrophages and may accelerate wound healing by transferring exosome-derived microRNA.

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