scholarly journals Skin protective effects of RM191A, a novel superoxide dismutase mimetic

2020 ◽  
Author(s):  
Artur Shariev ◽  
Alistair J. Laos ◽  
Donna Lai ◽  
Sheng Hua ◽  
Anna Zinger ◽  
...  

AbstractSuperoxide dismutase (SOD) is known to be protective against oxidative stress-mediated skin dysfunction. Here we explore the potential therapeutic activities of RM191A, a novel SOD mimetic, on skin. RM191A is a water soluble, dimeric copper (Cu2+-Cu3+)-centred polyglycine coordination complex. It displays 10-fold higher superoxide quenching activity compared to SOD as well as significant anti-inflammatory activity through beneficial modulation of several significant inflammatory pathways in cells.We tested the therapeutic potential of RM191A in a topical gel using a human skin explant model and observed that it significantly inhibits UV-induced DNA damage in the epidermis and dermis, including cyclobutane pyrimidine dimers (CPD), 8-oxo-guanine (8-oxoG) and 8-nitroguanine (8NGO). RM191A topical gel is found to be safe and non-toxic in mice following month-long daily dosing at 0.19 mL/kg body weight. Moreover, it significantly accelerates excisional wound healing, and reduces 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation in mice.HighlightsSuperoxide dismutase mimetic RM191A is a highly stable copper (Cu2+-Cu3+)-polyglycine coordination complexRM191A exhibits potent antioxidant (10-fold more than that of superoxide dismutase) properties in vitroRM191A exhibits potent anti-inflammatory properties in vitro and in vivoRM191A protects human skin explants against UV-induced oxidative stress and DNA damageRM191A is non-toxic and readily bioavailable in miceRM191A attenuates TPA-induced skin inflammation and improves wound healing in mice

2015 ◽  
Vol 18 (4) ◽  
pp. 578 ◽  
Author(s):  
Bradley S Simpson ◽  
Xianling Luo ◽  
Jiping Wang ◽  
Yunmei Song ◽  
David Claudie ◽  
...  

Purpose: We have previously reported that the Australian Northern Kaanju (Kuuku I’yu) medicinal plant Dodonaea polyandra has anti-inflammatory activity. This is attributed largely to the presence of clerodane diterpenoids contained within the leaf resin. We envisaged developing a topical preparation to treat indications relating to skin inflammation. However, it was unknown whether the resin could be incorporated into a suitable dosage form while retaining the therapeutic value demonstrated in previous work. Therefore, the following study was undertaken to assess parameters of safety and efficacy for a prototype formulation containing the leaf resin extracted from D. polyandra. Methods: Using the assessment criteria of optimum appearance, tactile feeling, spreadability and odour, 78 different formulations were developed. Formulation stability was assessed using a centrifugal test with preparations displaying phase separation further modified or re-formulated. A prototype formulation containing 5% w/w plant resin was selected and subjected to in vitro release studies. This was quantified through HPLC analysis using two major bioactive diterpenoids as reference. The prototype formulation was tested for efficacy in a TPA-induced acute murine skin inflammation model as well as a 3D human skin model for irritancy/toxicity (Epiderm™). Results: The prototype resin cream was a chartreuse-coloured homogenous semisolid preparation that was readily spreadable upon contact with skin with no sensation of tackiness, residual greasiness, or irritation. The optimized cream showed no phase separation after 30 min centrifugation at 825 g. In the TPA-induced inflammation model, the resin formulation significantly reduced ear thickness and interleukin-1 beta levels in mouse ear tissue. The 5% w/w resin cream formulation showed no irritancy in a 3D human skin model. Conclusions: Our results demonstrate that bioactive resin from D. polyandra can be formulated into a stable and non-irritant semi-solid dosage form and reduce parameters of acute skin inflammation in vivo. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.


2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Anca D. Farcaș ◽  
Augustin C. Moț ◽  
Alina E. Pârvu ◽  
Vlad Al. Toma ◽  
Mirel A. Popa ◽  
...  

Known for centuries throughout the world, Plantago species have long been used as traditional herbal remedies for many diseases related to inflammatory conditions of the skin, respiratory and digestive tract, or even malignancy. This study is aimed first at investigating the in vitro antioxidant and regenerative effects of Plantago sempervirens Crantz hydroalcoholic extract followed by an in vivo experiment using a turpentine oil-induced inflammation model. The in vitro evaluation for antioxidant activity was performed using classical assays such as DPPH and TEAC scavenging assays but also EPR, and the total phenolic content was determined using the Folin-Ciocalteu reagent. The wound healing assay was performed on human cells (Human EA.hy926). Besides, the prooxidant activity was determined using a method which involves in situ free radical generation by laccase and the oxidation of haemoglobin. On turpentine oil-induced inflammation in rats, the in vivo effects of three doses of P. sempervirens extracts (100%, 50%, and 25%) were assessed by measuring oxidative stress (MDA, TOS, OSI, NO, CAT, and SOD) and inflammatory (CRP, WBC, and NEU) parameters. Having a rich polyphenolic content, the xerophyte P. sempervirens exhibited a strong in vitro antioxidant activity by scavenging radicals, enhancing cell regeneration, and reducing oxidative stress markers. Diluted P. sempervirens extract (25%) exhibited the best antioxidant, wound healing, and anti-inflammatory activity.


Nanomedicine ◽  
2020 ◽  
Vol 15 (17) ◽  
pp. 1671-1685 ◽  
Author(s):  
Mohamad Allaw ◽  
Maria Pleguezuelos-Villa ◽  
Maria Letizia Manca ◽  
Carla Caddeo ◽  
Matteo Aroffu ◽  
...  

Aim: The moisturizing properties of glycerol, the penetration enhancing capability of propylene glycol and the bioadhesive properties of mucin were combined to improve the carrier capabilities of transfersomes and the efficacy of mangiferin in the treatment of skin lesions. Materials & methods: Mangiferin was incorporated in transfersomes and glycoltransfersomes, which were also modified with mucin. The physico–chemical features were assessed, along with the efficacy against oxidative stress and skin wounds in vitro and in vivo. Results: Glycoltransfersomes promoted the deposition of mangiferin in epidermis and dermis, protected fibroblasts from oxidative stress and stimulated their proliferation. The wound healing and anti-inflammatory efficacy of glycoltransfersomes were confirmed in vivo. Conclusion: Results confirmed the potential of glycoltransfersomes in preventing/treating of skin lesions.


Author(s):  
Hoda Keshmiri Neghab ◽  
Mohammad Hasan Soheilifar ◽  
Gholamreza Esmaeeli Djavid

Abstract. Wound healing consists of a series of highly orderly overlapping processes characterized by hemostasis, inflammation, proliferation, and remodeling. Prolongation or interruption in each phase can lead to delayed wound healing or a non-healing chronic wound. Vitamin A is a crucial nutrient that is most beneficial for the health of the skin. The present study was undertaken to determine the effect of vitamin A on regeneration, angiogenesis, and inflammation characteristics in an in vitro model system during wound healing. For this purpose, mouse skin normal fibroblast (L929), human umbilical vein endothelial cell (HUVEC), and monocyte/macrophage-like cell line (RAW 264.7) were considered to evaluate proliferation, angiogenesis, and anti-inflammatory responses, respectively. Vitamin A (0.1–5 μM) increased cellular proliferation of L929 and HUVEC (p < 0.05). Similarly, it stimulated angiogenesis by promoting endothelial cell migration up to approximately 4 fold and interestingly tube formation up to 8.5 fold (p < 0.01). Furthermore, vitamin A treatment was shown to decrease the level of nitric oxide production in a dose-dependent effect (p < 0.05), exhibiting the anti-inflammatory property of vitamin A in accelerating wound healing. These results may reveal the therapeutic potential of vitamin A in diabetic wound healing by stimulating regeneration, angiogenesis, and anti-inflammation responses.


Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
F Epifano ◽  
S Genovese ◽  
L Zhao ◽  
V Dang La ◽  
D Grenier

Author(s):  
Kiptiyah Kiptiyah ◽  
Widodo Widodo ◽  
Gatot Ciptadi ◽  
Aulanni’am Aulanni’Am ◽  
Mohammad A. Widodo ◽  
...  

AbstractBackgroundWe investigated whether 10-gingerol is able to induce oxidative stress in cumulus cells.MethodsFor the in-vitro research, we used a cumulus cell culture in M199, containing 10-gingerol in various concentrations (0, 12, 16, and 20 µM), and detected oxidative stress through superoxide dismutase (SOD) activity and malondialdehyde (MDA) concentrations, with incubation periods of 24, 48, 72, and 96 h. The obtained results were confirmed by in-silico studies.ResultsThe in-vitro data revealed that SOD activity and MDA concentration increased with increasing incubation periods: SOD activity at 0 µM (1.39 ± 0.24i), 12 µM (16.42 ± 0.35ab), 16 µM (17.28 ± 0.55ab), 20 µM (17.81 ± 0.12a), with a contribution of 71.1%. MDA concentration at 0 µM (17.82 ± 1.39 l), 12 µM (72.99 ± 0.31c), 16 µM (79.77 ± 4.19b), 20 µM (85.07 ± 2.57a), with a contribution of 73.1%. Based on this, the in-silico data uncovered that 10˗gingerol induces oxidative stress in cumulus cells by inhibiting HTR1A functions and inactivating GSK3B and AKT˗1.Conclusions10-gingerol induces oxidative stress in cumulus cells through enhancing SOD activity and MDA concentration by inhibiting HTR1A functions and inactivating GSK3B and AKT˗1.


2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Andra-Diana Andreicut ◽  
Alina Elena Pârvu ◽  
Augustin Cătălin Mot ◽  
Marcel Pârvu ◽  
Eva Fischer Fodor ◽  
...  

Oxidative stress and inflammation are interlinked processes. The aim of the study was to perform a phytochemical analysis and to evaluate the antioxidant and anti-inflammatory activities of ethanolic Mahonia aquifolium flower (MF), green fruit (MGF), and ripe fruit (MRF) extracts. Plant extract chemical composition was evaluated by HLPC. A DPPH test was used for the in vitro antioxidant activity. The in vivo antioxidant effects and the anti-inflammatory potential were tested on a rat turpentine oil-induced inflammation, by measuring serum nitric oxide (NOx) and TNF-alpha, total oxidative status (TOS), total antioxidant reactivity (TAR), oxidative stress index (OSI), 3-nitrothyrosine (3NT), malondialdehyde (MDA), and total thiols (SH). Extracts were administrated orally in three dilutions (100%, 50%, and 25%) for seven days prior to inflammation. The effects were compared to diclofenac. The HPLC polyphenol and alkaloid analysis revealed chlorogenic acid as the most abundant compound. All extracts had a good in vitro antioxidant activity, decreased NOx, TOS, and 3NT, and increased SH. TNF-alpha was reduced, and TAR increased only by MF and MGF. MDA was not influenced. Our findings suggest that M. aquifolium has anti-inflammatory and antioxidant effects that support the use in primary prevention of the inflammatory processes.


Author(s):  
Daisy Liu

Snow fungus, Tremella fuciformis, has been demonstrated to have numerous health benefits including purported chemopreventive properties due to free radical-scavenging ability. Protective effects derived from snow fungus polysaccharides are evaluated on Chinese hamster lung fibroblasts (CCL-39) exposed to carcinogen benzo[a]pyrene known to cause free radical formation and oxidative stress to cells. In this experiment, it was hypothesized that the naturally occurring polysaccharides in snow fungus are able to protect against or reduce oxidative stress-induced DNA damage. Polysaccharides were isolated through an alkaline extraction and in-vitro digestion. DNA damage was measured using the single-cell gel electrophoresis comet assay after exposure to benzo[a]pyrene and polysaccharide extract to lung fibroblasts. Results were calculated using the mean and standard deviation data of tail length and area, respectively. Each damaged cell was measured and analyzed through ImageJ Editing Software. The results indicate a promising trend which depict snow fungus polysaccharides yielding lower levels of DNA damage compared to cells exposed to benzo[a]pyrene and compared to the negative control (phosphate buffered saline and Dulbecco’s cell medium). This study suggests polysaccharides from Tremella fuciformis could truly prevent cellular DNA damage by protecting against oxidative stress.


2018 ◽  
Author(s):  
Ilias Marmouzi ◽  
El Mostafa Karym ◽  
Rachid Alami ◽  
Meryem El Jemli ◽  
Mourad Kharbach ◽  
...  

AbstractBackgroundTherapy combination is defined as disease treatment with two or more medication to acheive efficacy with lower doses or lower toxicity. Regarding its reported toxicities and efficacy, the Essential Oils (EOs) from Syzygium aromaticum (SA) and Pelargonium graveolens (PG) were combined for in vitro and in vivo assays and toxicities.MethodsThe Essential Oils and mixture were tested for in vivo/in vitro antioxidant and anti-inflammatory activities. The assays included the animal model of acute inflammation (carrageenan model), the protective effect on H2O2/Sodium nitroprissude induced stress in Tetrahymena pyriformis, and the in vitro antioxidant assays.ResultsThe chemical analysis of the investigated Oils has lead to the identification of Eugenol (74.06%), Caryophyllene (11.52%) and Carvacrol acetate (7.82%) as the major element in SA; while PG was much higher in Citronellol (30.77%), 10-epi-γ-Eudesmol (22.59%), and Geraniol (13.95%). In our pharmacological screening of samples, both Oils demonstrated good antioxidant effects. In vivo investigation of the antioxidant activity in the protozoa model (T. pyriformis) demonstrated a lesser toxic effect of EOs mixture with no significant differences when oxidative stress markers and antioxidant enzymes (MDA, SOD and CAT) were evaluated. On the other hand the in vivo model of inflammatory response to carrageenan demonstrated a good inhibitory potential of both EOs. The EOs Mixture demonstrated equivalent bioactivity with lower toxic effect and minimal risk for each compound.ConclusionsThe results from this study indicate that EOs mixture from SA and PG demonstrated promising modulatory antioxidant/anti-inflammatory effect, which suggest an efficient association for therapy.


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