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Quercetin and wound healing

Quercetin and wound healing

Received : 08 August The Quercetkn results confirmed that Flaxseeds is a therapeutic Wounr for helping to heal pressure ulcers. Cutaneous wound healing activity of a herbal ointment containing the leaf extract of Jatropha curcas L. College, Tamil Nadu, India, for providing the necessary facilities for the laboratory work.

Quercetin and wound healing -

Cited by. Download options Please wait Supplementary information PDF K. Article type Paper. Submitted 28 Mar Accepted 21 Apr First published 26 Apr Download Citation.

Nanoscale , , 10 , BibTex EndNote MEDLINE ProCite ReferenceManager RefWorks RIS. Request permissions. PEGylated graphene oxide-mediated quercetin-modified collagen hybrid scaffold for enhancement of MSCs differentiation potential and diabetic wound healing J. Social activity. Search articles by author Jing Chu.

Panpan Shi. Wenxia Yan. Jinping Fu. Zhi Yang. Chengmin He. Welcome to NIScPR Online Periodicals Repository You can now access full text articles from research journals published by CSIR-NIScPR! Full text facility is provided for all nineteen research journals viz.

NOPR also hosts three Popular Science Magazines viz. Show full item record. Quercetin accelerated cutaneous wound healing in rats by increasing levels of VEGF and TGF-β1.

B Cell viability of fibroblasts treated with QCT GNP or QCT GNP-Ga for 24, 48, and 72 h. C The uncovered aera and D representative images of wound-healing assay of fibroblasts treated with GNP, QCT GNP or QCT GNP-Ga. E Western blot analysis and E statistical results of COL1, ELN protein expressions in fibroblasts treated with GNP, QCT GNP or QCT GNP-Ga.

G qRT-PCR analysis of COL1, ELN mRNA expressions in fibroblasts treated with GNP, QCT GNP or QCT GNP-Ga for 48 h. Since that bacterial proliferation at the wound site is one of the major reasons for delayed healing and abnormal scarring Frykberg and Banks, ; Zhang et al.

et al. The surface of the agarose medium was coated with QCT GNP-Ga and then inoculated with S. aureus and E. coli to observe its anti-bacterial activity. After 24 h of constant temperature culture at 37°C, many bacterial colonies were observed on the culture dish in the QCT GNP group, while only a few bacterial colonies were observed in the QCT GNP-Ga group.

At 48 h, the culture dish in the QCT GNP was covered with bacterial colonies, while only a few bacterial colonies were formed in the QCT GNP-Ga group Figures 3A, B. Further statistics analysis showed that the number of bacterial colonies formed in the QCT GNP-Ga group at either 24 or 48 h was significantly smaller than that in the QCT GNP group.

The same results were obtained for S. coli Figures 3C, D. FIGURE 3. Anti-bacterial activity of QCT GNP-Ga. A, B Images and C, D statistical results of colony forming unit CFU of E.

coli and S. aureus treated with QCT GNP or QCT GNP-Ga. It has been demonstrated that a proper inflammatory response is required for skin wound repair Xu et al.

Macrophages are the most functionally diverse cells for generation and resolution of inflammation by phenotype polarization. Classically-activated macrophages M1 secrete high levels of pro-inflammatory cytokines like IL-1β, IL-6, and TNF-α to exhibit pro-inflammatory properties Koh and DiPietro, , whereas alternatively-activated macrophages M2 that secret high level IL and TGF-β and low-level IL play a role in resolution of inflammation Gensel and Zhang, High population of macrophages could lead to sustained inflammation that might delay the process of wound healing Guo et al.

Therefore, we wondered whether QCT GNP-Ga played a role in the regulation of macrophage polarization. To this end, mouse RAW Afterwards, these macrophages were treated with QCT GNP-Ga for 5 days to observe its effect on the polarization of mouse macrophages.

Flow cytometry analysis revealed that, after the induction by LPS, CD86 was highly-expressed in cells, while CD was merely expressed.

After the treatment with QCT GNP-Ga, the expression of CD86 in RAW Further ELISA assay showed that, in response to LPS stimulation, the expression of TNF-α and MCP-1 was significantly lower in the QCT GNP-Ga group than that in the GNP group and GNP-Ga group, while the expression of TGF-β3 and IL-4 was prominently increased in QCT GNP-Ga group Figure 4B.

In addition, qRT-PCR analysis showed that in response to LPS stimulation, the mRNA levels of TNF-α, MCP-1 and iNOS were significantly lower in the QCT GNP-Ga group than those in the GNP group and GNP-Ga group, while the mRNA levels of TGF-β3, IL-4 and Arg-1 were significantly higher than those in the GNP group and GNP-Ga group Figure 4C.

Similarly, immunoblotting analysis proved that the expression of Arg-1 was prominently increased after the treatment with QCT GNP-Ga Figures 4D, E. Taken together, these results demonstrated that QCT GNP-Ga could induce the phenotype switch of macrophages from M1 to M2, so that sustained inflammation could be mitigated to facilitate the process of wound healing.

FIGURE 4. Induction of macrophages from M1 to M2 phenotype by QCT GNP-Ga. A Representative images of FCM analysis of LPS induced RAW B EILSA analysis of TNF-α, MCP-1, TGF-β3, and IL-4 protein expressions in LPS induced RAW C qPCR analysis of TNF-α, MCP-1, iNOS, TGF-β3, IL-4, Arg-1 mRNA expressions in LPS induced RAW D Western blot analysis and E statistical results of ARG1 protein expressions in LPS induced RAW Thereafter, we went on to elucidate the mechanism underlying the role of QCT GNP-Ga in the regulation of macrophages polarization.

To this end, QCT GNP-Ga was added to the medium of the RAW It was found that the protein expression of TGFβR2 was increased after the treatment with QCT GNP-Ga compared with control GNP group Figures 5A, B. In consistent, immunofluorescence staining analysis also showed that the expression of TGFβR2 was enhanced after the treatment with QCT GNP-Ga Figure 5C.

In line with the upregulation of TGFβR2 after QCT GNP-Ga treatment, the phosphorylation of Smad2 was also increased, indicating the activation of TGFβ-Smad signaling by QCT GNP-Ga, and this effect could be effectively blocked by TGFβR2 inhibitor LY Figures 5D, E.

Flow cytometry analysis revealed that the expression of CD in cells increased after the treatment with QCT GNP-Ga, while its expression was significantly reduced by the inhibitor LY Figure 5F. In addition, while QCT GNP-Ga treatment induced prominent downregulation of the expression and secretion of TNF-α and MCP-1, as well as the upregulation of the expression and secretion of TGF-β3 and IL-4, co-treatment with TGFβR2 inhibitor LY was capable of reversing this alteration trend Figures 5G, H.

FIGURE 5. A Western blot analysis, B statistical results, and C immunofluorescent staining analysis of TGFβR2 protein expressions in RAW D Western blot analysis and E statistical results of TGFβR2, p-Smad2, and Smad2 protein expressions in RAW F Representative images of FCM analysis of RAW G, H Relative expression and secretion of TNF-α, MCP-1, TGF-β3 and IL-4 after the treatment with GNP or QCT GNP-Ga or with LY in LPS-stimulated macrophage.

Given that QCT GNP-Ga could simultaneously potentiate fibroblast function, exert anti-bacterial property, and induce macrophages polarization from M1 to M2 to suppress sustained inflammation, we proposed that QCT GNP-Ga might play a cardinal role in facilitating wound healing and restraining scar formation in vivo.

A skin wound model was established on the back skin of SD rats, and then the injectable material for repairing skin wound prepared with the gelatin hydrogel loaded with QCT GNP-Ga.

After 14 days of injection, the average rates of wound healing in both the GNP-Ga group and the QCT GNP-Ga groups were higher than that in the GNP group Figures 6A, D. The results of HE staining showed that many fibrous scars were formed at wound locations in the GNP group, and local fibrocytes proliferated and were arranged in a compact and disordered manner.

In contrary, the scar tissues in the GNP-Ga group were partially reduced, and were further reduced in the QCT GNP-Ga group Figure 6B. Concurrent immunohistochemical staining analysis showed that the TNFα-positive cells in the control group were distributed in scar tissues, while the TNFα-positive cells in the QCT GNP-Ga group were significantly reduced Figures 6C, E , indicating that the reduction of scar tissues was associated with the inhibition of inflammatory reactions.

Taken together, QCT GNP-Ga exerts great potential in facilitating wound healing and restraining scar formation in pre-clinical rat model. FIGURE 6. In vivo repair effect of QCT GNP-Ga on rat skin wounds. A Representative images of wound healing covered by GNP, GNP-Ga or QCT GNP-Ga from 0 to 14 days and D quantitative results.

In case of an open skin wound, it is often accompanied with bacterial attachment, causing wound infection and resultant severe scars Leng et al.

In addition, the impaired wound-healing function of fibroblast and sustained inflammatory reactions also restrain the process of wound closure and increase the incidence or severity of scar Morris et al.

In the present study, a novel anti-bacterial drug-loaded hydrogel nanoparticle was developed, which could effectively facilitate wound closure, inhibit bacterial proliferation, and ameliorate scar formation, which was related to its role in regulating macrophage polarization, providing a promising choice for the treatment of wound.

Since that nanoparticles have multiple advantages including high drug loading capacity, good biocompatibility, and the ability of the controlling drug release, they have been widely employed in investigations on tissue repair.

As a drug carrier or antibacterial active substance, nanoparticles are applied to skin damage repair by mixing with hydrogel to form composite hydrogel Sun et al.

Silver particles, titanium oxide, gentamicin-containing nanoparticles, curcumin-containing nanoparticles, and other composite hydrogels have been confirmed to have anti-bacterial and wound healing-promoting effects Javanmardi et al.

In recent years, gallium ion has been found to be advantageous in the field of antibacterial materials Vinuesa and McConnell, Due to the unique anti-microbial mechanism of gallium, it can overcome the problem of resistance to traditional antibiotics, such as the prevention of drug absorption due to the permeability of bacterial cell wall.

Gallium ions can imitate the metabolic pathway of iron ions to promote cell absorption, whereas cannot be reduced like iron ions Kurtuldu et al. Therefore, the proliferation of bacteria is inhibited when the oxidation-reduction process necessary for the synthesis of the DNA and protein of bacteria is interrupted.

In addition to the recognized broad-spectrum bactericidal activity of gallium ions, small doses of gallium ions can also suppress inflammatory reactions Ma and Fu, ; Goss et al. Besides, some studies have demonstrated that gallium ions can also promote collagen synthesis and cell migration, thus facilitating the process of wound healing Kircheva and Dudev, ; Castilla-Amoros et al.

In this study, our data proved that the gallium ion-modified gelatin nanoparticles were efficient in promoting the wound-healing function of fibroblast, suppressing bacterial proliferation and inhibiting inflammatory reactions, providing an experimental foundation for wound treatment.

Quercetin is flavonoid rich in a variety of foods and has multiple biological characteristics, including anti-inflammatory reaction, anti-oxidative and some other properties Liu et al.

Some studies have pointed out that quercetin can reduce the generation of TNF-α, IL-6 and IL-1 in mononuclear U cells induced by LPS Okoko and Oruambo, In addition, quercetin can inhibit the expressions of inflammation-related genes in RAW The study by Gupta et al.

Moreover, Guan et al. Supplementary to these previous reports, our data for the first time proved that quercetin was also effective in inhibiting the inflammatory reactions during skin scar formation.

Inflammatory response participates in wound healing and scar formation, and macrophages that undergo phenotypic and functional changes play a critical role. The persistent existence of pro-inflammatory M1 macrophage in regional skin could prominently delay would healing Ishida et al.

To suppress the infiltration of pro-inflammatory macrophage and induce macrophage polarization from M1 to M2 type in late phase is beneficial for wound healing and reduced scar formation. In the present study, a new gallium ion-modified drug-loaded hydrogel nanoparticle was developed aiming to ameliorate infection and scar formation during the process of wound healing.

Our data demonstrated that gallium-modified gelatin nanoparticles loaded with quercetin could promote skin wound healing via the regulation of bacterial proliferation and macrophage polarization, and this preparation might be a promising choice to treat wound and suppress scar formation simultaneously, which needs further confirmation by clinical trial in the future.

The raw data supporting the conclusion of this article will be made available by the authors, without undue reservation. The animal study was reviewed and approved by Laboratory Animal Welfare and Ethics Committee of Fourth Military Medical University.

NY: Methodology, investigation, formal analysis, writing—Original draft. NS: Methodology, investigation, writing—Original draft. ZY: Conceptualization, resources, methodology. HL: Conceptualization, supervision, resources, funding acquisition.

WG: Conceptualization, writing—Original draft, writing—Review and editing, supervision, funding acquisition. This work was supported by Natural Science Foundation of China , Natural Science Foundation of Shaanxi Province JQ , Natural Science Foundation of Jiangsu Province BK , and Postdoctoral Science Foundation of China M The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The handling editor, KL, declared a shared affiliation with the authors NS and HL at the time of review. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Alster, T. Laser scar revision: Comparison study of nm pulsed dye laser with and without intralesional corticosteroids.

Dermatol Surg. PubMed Abstract CrossRef Full Text Google Scholar. Atiyeh, B. Nonsurgical management of hypertrophic scars: Evidence-based therapies, standard practices, and emerging methods. Aesthetic Plast. Bui, V. Dissolving microneedles for long-term storage and transdermal delivery of extracellular vesicles.

Biomaterials , Burdusel, A. Inorganic nanoparticles in bone healing applications. Pharmaceutics 14 4 , Castilla-Amoros, L.

Exploring the chemical reactivity of gallium liquid metal nanoparticles in galvanic replacement. Chanjitwiriya, K. PLoS One 15 8 , e Clarkin, O.

Novel injectable gallium-based self-setting glass-alginate hydrogel composite for cardiovascular tissue engineering.

Nanotechnology based platforms have gained hdaling insights into the development of effective modes of woumd delivery systems for Querxetin wounds Quercetin and wound healing related pathologies. Wlund Quercetin and wound healing in nanodimensioned materials or nanoparticles Quuercetin Quercetin and wound healing a znd attractive and Brain-boosting nutrients strategy for the Carbs and sports hydration of optimized pharmaceutical formulations. The in vivo acute dermal toxicity study did not produce any overt indications of toxicity as compared with control rats. Furthermore, the restoration of biomarkers hydroxyproline and hexosamine content significantly proved increased re-epithelialization and collagen formation. The histopathological investigations on wounds treated with drug-loaded gel demonstrated efficient healing, as evidenced by the deficit of inflammation, established fibrous tissues, well-organized fibroblasts, and blood capillaries. This is a preview of subscription content, log in via an institution to check access. Rent this article via DeepDyve. Quercetin and wound healing

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