Protective Effects of Curcumin against Oxidative Damage on Skin Cells In Vitro: Its Implication for Wound Healing

Background: Chronic inflammation and lack of angiogenesis are the important pathological mechanisms in deep tissue injury (DTI). Curcumin is a well-known anti-inflammatory and antioxidant agent. However, curcumin is unstable under acidic and alkaline conditions, and can be rapidly metabolized and excreted in the bile, which shortens its bioactivity and efficacy. Objective: This study aimed to prepare curcumin-loaded poly (lactic-co-glycolic acid) nanoparticles (CPNPs) and to elucidate the protective effects and underlying mechanisms of wound healing in DTI models. Methods: CPNPs were evaluated for particle size, biocompatibility, in vitro drug release and their effect on in vivo wound healing. Results : The results of in vivo wound closure analysis revealed that CPNP treatments significantly improved wound contraction rates (p<0.01) at a faster rate than other three treatment groups. H&E staining revealed that CPNP treatments resulted in complete epithelialization and thick granulation tissue formation, whereas control groups resulted in a lack of compact epithelialization and persistence of inflammatory cells within the wound sites. Quantitative real-time PCR analysis showed that treatment with CPNPs suppressed IL-6 and TNF-α mRNA expression, and up-regulated TGF-β, VEGF-A and IL-10 mRNA expression. Western blot analysis showed up-regulated protein expression of TGF-β, VEGF-A and phosphorylatedSTAT3. Conclusion: Our results showed that CPNPs enhanced wound healing in DTI models, through modulation of the JAK2/STAT3 signalling pathway and subsequent upregulation of pro-healing factors.

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Combined Effects of Carotenoids and Polyphenols in Balancing the Response of Skin Cells to UV Irradiation

Molecules ◽

10.3390/molecules26071931 ◽

2021 ◽

Vol 26 (7) ◽

pp. 1931

Author(s):

Glenda Calniquer ◽

Marina Khanin ◽

Hilla Ovadia ◽

Karin Linnewiel-Hermoni ◽

David Stepensky ◽

...

Keyword(s):

Cell Damage ◽

Plasma Concentrations ◽

Dermal Fibroblasts ◽

Carnosic Acid ◽

Rosemary Extract ◽

Protective Effects ◽

Skin Cells ◽

Tomato Extract ◽

Clinical Experiments

Oral carotenoids and polyphenols have been suggested to induce photo-protective effects. The aim of the study was to test whether the combination of carotenoids and polyphenols produce greater protective effects from UV-induced damage to skin cells. Such damage is characterized by inflammation and oxidative stress; thus, the photo-protective effect can be partially explained by modulating the nuclear factor kappa B (NFκB) and antioxidant response element/Nrf2 (ARE/Nrf2) transcription systems, known as important regulators of these two processes. Indeed, it was found in keratinocytes that carotenoids and polyphenols inhibit UVB-induced NFκB activity and release of cytokine IL-6. A combination of tomato extract with rosemary extract inhibited UVB-induced release of IL-6 more than each of the compounds alone. Moreover, this combination synergistically activated ARE/Nrf2 transcription systems. Inflammatory cytokines such as IL-6 and TNFα induce the expression of matrix metalloproteinases (MMPs), which leads to collagen breakdown; thus, it is important to note that carnosic acid reduced TNFα-induced MMP-1 secretion from human dermal fibroblasts. The in vitro results suggest beneficial effects of phytonutrient combinations on skin health. To assure that clinical experiments to prove such effects in humans are feasible, the human bioavailability of carotenoids from tomato extract was tested, and nearly a twofold increase in their plasma concentrations was detected. This study demonstrates that carotenoids and polyphenols cooperate in balancing UV-induced skin cell damage, and suggests that NFκB and ARE/Nrf2 are involved in these effects.

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Strawberry and Achenes Hydroalcoholic Extracts and Their Digested Fractions Efficiently Counteract the AAPH-Induced Oxidative Damage in HepG2 Cells

International Journal of Molecular Sciences ◽

10.3390/ijms19082180 ◽

2018 ◽

Vol 19 (8) ◽

pp. 2180 ◽

Cited By ~ 5

Author(s):

María Ariza ◽

Tamara Forbes-Hernández ◽

Patricia Reboredo-Rodríguez ◽

Sadia Afrin ◽

Massimiliano Gasparrini ◽

...

Keyword(s):

Biological Activity ◽

Oxidative Damage ◽

Hepg2 Cells ◽

In Vitro Digestion ◽

Protective Effects ◽

Beneficial Effects ◽

Positive Effects ◽

Digestion Process ◽

Phytochemical Compounds

Strawberry fruits are highly appreciated by consumers worldwide due to their bright red color, typical aroma, and juicy texture. While the biological activity of the complete fruit has been widely studied, the potential beneficial effects of the achenes (commonly named seeds) remain unknown. In addition, when raw fruit and achenes are consumed, the digestion process could alter the release and absorption of their phytochemical compounds, compromising their bioactivity. In the present work, we evaluated the protective effects against oxidative damage of nondigested and digested extracts from strawberry fruit and achenes in human hepatocellular carcinoma (HepG2) cells. For that purpose, cells were treated with different concentration of the extracts prior to incubation with the stressor agent, AAPH (2,2′-azobis(2-amidinopropane) dihydrochloride). Subsequently, intracellular accumulation of reactive oxygen species (ROS) and the percentage of live, dead, and apoptotic cells were determined. Our results demonstrated that all the evaluated fractions were able to counteract the AAPH-induced damage, suggesting that the achenes also present biological activity. The positive effects of both the raw fruit and achenes were maintained after the in vitro digestion process.

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The effect of local hyperglycemia on skin cells in vitro and on wound healing in euglycemic rats

Journal of Surgical Research ◽

10.1016/j.jss.2016.08.060 ◽

2016 ◽

Vol 206 (2) ◽

pp. 418-426 ◽

Cited By ~ 10

Author(s):

Carla R. Kruse ◽

Mansher Singh ◽

Jens A. Sørensen ◽

Elof Eriksson ◽

Kristo Nuutila

Keyword(s):

Wound Healing ◽

Skin Cells

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Salivary Trefoil Factor Family (TFF) Peptides and Their Roles in Oral and Esophageal Protection: Therapeutic Potential

International Journal of Molecular Sciences ◽

10.3390/ijms222212221 ◽

2021 ◽

Vol 22 (22) ◽

pp. 12221

Author(s):

Werner Hoffmann

Keyword(s):

Wound Healing ◽

Therapeutic Potential ◽

Artificial Saliva ◽

Human Saliva ◽

Immune Defense ◽

Protective Effects ◽

Trefoil Factor Family ◽

Tff Peptides ◽

Antimicrobial Barrier

Human saliva is a complex body fluid with more than 3000 different identified proteins. Besides rheological and lubricating properties, saliva supports wound healing and acts as an antimicrobial barrier. TFF peptides are secreted from the mucous acini of the major and minor salivary glands and are typical constituents of normal saliva; TFF3 being the predominant peptide compared with TFF1 and TFF2. Only TFF3 is easily detectable by Western blotting. It occurs in two forms, a disulfide-linked homodimer (Mr: 13k) and a high-molecular-mass heterodimer with IgG Fc binding protein (FCGBP). TFF peptides are secretory lectins known for their protective effects in mucous epithelia; the TFF3 dimer probably has wound-healing properties due to its weak motogenic effect. There are multiple indications that FCGBP and TFF3-FCGBP play a key role in the innate immune defense of mucous epithelia. In addition, homodimeric TFF3 interacts in vitro with the salivary agglutinin DMBT1gp340. Here, the protective roles of TFF peptides, FCGBP, and DMBT1gp340 in saliva are discussed. TFF peptides are also used to reduce radiotherapy- or chemotherapy-induced oral mucositis. Thus, TFF peptides, FCGBP, and DMBT1gp340 are promising candidates for better formulations of artificial saliva, particularly improving wound healing and antimicrobial effects even in the esophagus.

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In vitro protective effects of resveratrol against oxidative damage in human erythrocytes

Biochimica et Biophysica Acta (BBA) - Biomembranes ◽

10.1016/j.bbamem.2014.09.009 ◽

2015 ◽

Vol 1848 (1) ◽

pp. 76-82 ◽

Cited By ~ 23

Author(s):

M. Suwalsky ◽

F.Villena ◽

M.J. Gallardo

Keyword(s):

Oxidative Damage ◽

Human Erythrocytes ◽

Protective Effects

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After In Vitro Digestion, Jackfruit Flake Affords Protection against Acrylamide-Induced Oxidative Damage

Molecules ◽

10.3390/molecules24183322 ◽

2019 ◽

Vol 24 (18) ◽

pp. 3322 ◽

Cited By ~ 1

Author(s):

Daofeng Qu ◽

Chu Liu ◽

Mengxue Jiang ◽

Lifang Feng ◽

Yuewen Chen ◽

...

Keyword(s):

Oxidative Stress ◽

Oxidative Damage ◽

High Performance ◽

In Vitro Digestion ◽

Protective Effects ◽

Physical Damage ◽

Before And After ◽

High Content Analysis ◽

High Level

Some studies have demonstrated that acrylamide (AA) was correlated with oxidative stress, resulting in physical damage. The jackfruit flake was an immature pulp that contained a high level of antioxidant activity. This study aimed to assess the defensive efficacy of jackfruit flake in AA-induced oxidative stress before and after simulated gastrointestinal digestion. Our results indicate that the total polyphenol content of Jackfruit flake digest (Digestive products of jackfruit flake after gastrointestinal, JFG) was diminished; however, JFG had raised the relative antioxidant capacity compared to Jackfruit flake extract (JFE). Additionally, the results of High Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS) implied that a proportion of compounds were degraded/converted into other unknown and/or undetected metabolites. Further, by high content analysis (HCA) techniques, JFG markedly reduced cytotoxicity and excessive production of reactive oxygen species (ROS) in cells, thereby alleviating mitochondrial disorders. In this study, it may be converted active compounds after digestion that had preferable protective effects against AA-induced oxidative damage.

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Huangbai Liniment Accelerated Wound Healing by Activating Nrf2 Signaling in Diabetes

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/4951820 ◽

2020 ◽

Vol 2020 ◽

pp. 1-20

Author(s):

Jingjing Zhang ◽

Rui Zhou ◽

Changpei Xiang ◽

Qiang Jia ◽

Hongwei Wu ◽

...

Keyword(s):

Wound Healing ◽

Oxidative Damage ◽

Drug Targets ◽

Diabetic Rats ◽

Diabetic Patients ◽

Diabetic Wound ◽

Antioxidant Genes ◽

Thioredoxin System ◽

Forsythia Suspensa

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-β1 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.

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