Resolvin D5 Protects Female Hairless Mouse Skin from Pathological Alterations Caused by UVB Irradiation.

Resolvin D5 (RvD5) is a lipid mediator that has been reported to present anti-inflammatory and pro-resolution properties. Evidence also supports its capability to enhance reactive oxygen species (ROS) production during bacterial infections, which would be detrimental in diseases driven by ROS. The biological activity of RvD5 and mechanisms against UVB irradiation skin pathology have not been investigated so far. Female hairless mice were treated intraperitoneally with RvD5 before UVB stimulus. RvD5 reduced skin edema in a dose-dependent manner as well as oxidative stress by increasing antioxidants (endogenous tissue antioxidant scavenging of cationic radical, iron reduction, catalase activity and reduced glutathione levels) and decreasing pro-oxidants (superoxide anion and lipid peroxidation). RvD5 antioxidant activity was accompanied by enhancement of Nrf2, HO-1 and NQO1 mRNA expression. RvD5 reduced the production of IL-1ß, TNF-α, TGF-ß, and IL-10. RvD5 also reduced the inflammatory cell counts, including mast cells and neutrophils/macrophages. The reduction of oxidative stress and inflammation resulted in diminished matrix metalloproteinase 9 activity, collagen degradation, epidermal thickening and sunburn cell development. Therefore, this study demonstrates, to our knowledge, the first body of evidence that RvD5 can be used to treat UVB skin pathology and unveils, at least in part, its mechanisms of action.

Bioadhesive Polymeric Films Containing Rhamnolipids, An Innovative Antimicrobial Topical Formulation.

Acne affects most of the world's population, causing an impact on the self-esteem of adolescents and young adults. One of the causes is the presence of the bacteria Cutibacterium acnes which are part of the natural microbiota of the skin. Topical treatments consist of anti-inflammatory and antibiotics, which could select resistant strains. Alternatives to the antibiotic are biocomposites that have antimicrobial activity like biosurfactants which are produced by bacteria. An innovative way of applying these compounds is bioadhesive polymeric films that adhere to the skin and release the active principle topically. Rhamnolipids have great potential to be used in the treatment of acne because they present antimicrobial activity against C. acnes in low and safe concentrations (MIC of 15.62 µg/mL, CBM of 31.25 µg/mL and CC50 of 181.93 µg/mL). Four films with different rhamnolipids concentrations (0.0; 0.1; 0.2; and 0.3%, w/w) were obtained as to visual appearance, mass variation, thickness, density, solubility, pH, water vapor transmission, mechanical properties (folding endurance, bioadhesion strength, tensile strength, elongation at break and Young's modulus), scanning electron microscopy and infrared. The results show that these formulations had a homogeneous appearance; elastic mechanical properties; pH similar to human skin and bioadhesive. The polymeric films containing rhamnolipids were effective against C. acnes, in the in vitro test, at the three concentrations tested, the film with the highest concentration (0.3%, w/w) being the most promising for presenting the highest antimicrobial activity. Thus, the polymeric film containing rhamnolipids has the potential to be used in the treatment of acne.

Development of trans-Chalcone loaded pectin/casein biodegradable microcapsules: Efficacy improvement in the management of experimental colitis.

Improved therapies for inflammatory bowel diseases are sorely needed. Novel therapeutic agents and the development of controlled release systems for targeted tissue delivery are interesting approaches to overcome these barriers. We investigated the activity of trans-chalcone (T) in acetic acid-induced colitis in mice and developed, characterized, and determined the therapeutic effect of pectin/casein polymer microcapsules containing T (MT) in a colitis mouse model. In vitro, compound release was achieved in simulated intestinal fluid but not in the simulated gastric fluid. In vivo, since T at the dose of 3 mg/kg but not 0.3 mg/kg ameliorated colitis, we next tested the effects of MT at 0.3 mg/kg (non-effective dose). MT, but not free T at 0.3 mg/kg, significantly improved colitis outcomes such as neutrophil recruitment, antioxidant capacity, cytokine production, and NF-kB activation. This translated into reduced macro and microscopic damage in the colon. T release from the microcapsules is mediated by a pH-dependent and pectinase-regulated mechanism that provide controlled and prolonged release of T. Moreover, MT lowered the required dose for T therapeutic effect, indicating that could be a suitable pharmaceutical approach to colitis treatment. This is the first demonstration that T or MT is effective at reducing the signs of colitis.

Aspirin-Triggered Resolvin D1 (AT-RvD1) Protects Mouse Skin against UVB-Induced Inflammation and Oxidative Stress.

Intense exposure to UVB radiation incites excessive production of reactive oxygen species (ROS) and inflammation. The resolution of inflammation is an active process orchestrated by a family of lipid molecules that includes AT-RvD1, a specialized proresolving lipid mediator (SPM). AT-RvD1 is derived from omega-3, which presents anti-inflammatory activity and reduces oxidative stress markers. The present work aims to investigate the protective effect of AT-RvD1 on UVB-induced inflammation and oxidative stress in hairless mice. Animals were first treated with 30, 100, and 300 pg/animal AT-RvD1 (i.v.) and then exposed to UVB (4.14 J/cm2). The results showed that 300 pg/animal of AT-RvD1 could restrict skin edema, neutrophil and mast cell infiltration, COX-2 mRNA expression, cytokine release, and MMP-9 activity and restore skin antioxidant capacity as per FRAP and ABTS assays and control O2•- production, lipoperoxidation, epidermal thickening, and sunburn cells development. AT-RvD1 could reverse the UVB-induced downregulation of Nrf2 and its downstream targets GSH, catalase, and NOQ-1. Our results suggest that by upregulating the Nrf2 pathway, AT-RvD1 promotes the expression of ARE genes, restoring the skin's natural antioxidant defense against UVB exposition to avoid oxidative stress, inflammation, and tissue damage.

Rosmarinus officinalis extract-loaded emulgel prevents UVB irradiation damage to the skin.

UVB-irradiation increases the risk of various skin disorders, therefore leading to inflammation and oxidative stress. In this sense, antioxidant-rich herbs such as Rosmarinus officinalis may be useful in minimizing the damage promoted by reactive oxygen species. In this work, we report the efficacy of a R. officinalis hydroethanolic extract (ROe)-loaded emulgel in preventing UVB-related skin damage. Total phenols were determined using Folin-Ciocalteu assay, and the main phytocomponents in the extract were identified by UHPLC-HRMS. Moreover, in vitro sun protection factor (SPF) value of ROe was also assessed, and we investigated the in vivo protective effect of an emulgel containing ROe against UVB-induced damage in an animal model. The ROe exhibited commercially viable SPF activity (7.56 ± 0.16) and remarkable polyphenolic content (24.15 ± 0.11 mg (Eq.GA)/g). HPLC-MS and UHPLC-HRMS results showcased that the main compounds in ROe were: rosmarinic acid, carnosic acid and carnosol. The evaluation of the in vitro antioxidant activity demonstrated a dose-dependent effect of ROe against several radicals and the capacity to reduce iron. Therefore, we demonstrated that topical application of the formulation containing ROe inhibited edema formation, myeloperoxidase activity, GSH depletion and maintained ferric reducing (FRAP) and ABTS scavenging abilities of the skin after UVB exposure.

Hydroethanolic Extract of Grape Peel from Vitis labrusca Winemaking Waste: Antinociceptive and Anti-Inflammatory Activities.

Research background: Extracts from grape pomace, including the wine, show many biological effects such as antioxidant and anti-inflammatory activities. Unfortunately, winemakers discard the bagasse, so the waste is not exploited, although it contains bioactive compounds with antioxidant and anti-inflammatory properties. The work aims to analyze the hydroethanolic extract of peels from Vitis labrusca agro-industrial waste and to evaluate its antinociceptive and anti-inflammatory properties. This study is relevant for reusing a residue and adding value to the grape economic chain. Experimental approach: A representative sample of pomace was obtained and the peels were used to produce the extract. The phenolic compounds were determined by mass spectrometry in multiple reaction monitoring mode and Folin-Ciocalteu colorimetric method, using gallic acid as standard. The biological analyses were carried out using mice orally treated with crude extract at doses of 30, 100 and 300 mg/kg. We evaluated mechanical hyperalgesia by the von Frey method, thermal heat hyperalgesia using a hot plate at 55 °C, paw edema using a pachymeter, and neutrophil recruitment by measurement of myeloperoxidase activity. The nephrotoxicity and hepatotoxicity were evaluated by biochemical analyses using blood samples that were collected after the Vitis labrusca administration. Results and conclusions: In all wet winemaking residues peel mass fraction was 75%, and in dry residues 59%. We identified nine anthocyanins (3-O-glucosides: peonidin, delphinidin, petunidin and malvidin; 3-p-coumaroyl-glucosides: cyanidin, peonidin, petunidin and malvidin, and malvidin-3,5-diglucoside), five flavonoids (apigenin-7-glucoside, luteolin-7-glucoside, quercetin-3-galactoside, isorhamnetin-3-glucoside and myricetin-3-rutinoside), and mass fraction of phenolic compounds, expressed as gallic acid equivalents, was 26.62 mg/g. In vivo assays showed that Vitis labrusca extract at mass fractions 100 and 300 mg/kg reduced carrageenan-induced mechanical and thermal hyperalgesia, 50% of the paw edema, and neutrophil recruitment. In addition, there were no indications of nephrotoxicity and hepatotoxicity. Our extract obtained from winemaking residue has analgesic and anti-inflammatory properties, related at least in part to the presence of phenolic compounds, and it is not toxic to renal and hepatic tissues. Novelty and scientific contribution: This bio-product can be used as an alternative to synthetic anti-inflammatory agents with the same pharmacological potential and fewer side effects. We demonstrated that Vitis labrusca winemaking waste can be used for the production of antinociceptive and anti-inflammatory products (nutraceutical, pharmaceutical and cosmetics) without toxicity, contributing to the environmental economy.

Pimenta pseudocaryophyllus (Gomes) Landrum extract inhibits inflammatory pain in mice: targeting neutrophil recruitment, oxidative stress, and cytokine production.

Pimenta pseudocaryophyllus (Gomes) Landrum is a Brazilian native plant. The mechanisms by which it promotes analgesia are unknown. We demonstrated the analgesic effect of P. pseudocaryophyllus dried extract (3 mg/kg; i.p.) in the following models of inflammatory pain (maximal inhibition): phenyl-p-benzoquinone (89%), formalin (72% - 1st phase and 96% - 2nd phase for flinches, and 50% - 1st phase and 71% - 2nd phase for licking behavior), complete Freund's adjuvant (95% - flinches and 33% - licking behavior), and carrageenin (56% - mechanical and 85% - thermal hyperalgesia) without motor impairment. Its analgesic effect depends on inhibiting neutrophil recruitment (95% - histopathology, 83% - myeloperoxidase activity, and 80% - LysM-eGFP mice), oxidative stress (86% - GSH and 98% - superoxide anion), and cytokine production (35% - IL-33, 80% - TNF-α, and 95% - IL-1ß). The present study advances in understanding the analgesic mechanisms of P. pseudocaryophyllus.

Therapeutic Potential of Controlled Delivery Systems in Asthma: Preclinical Development of Flavonoid-Based Treatments.

Asthma is a chronic disease with increasing prevalence and incidence, manifested by allergic inflammatory reactions, and is life-threatening for patients with severe disease. Repetitive challenges with the allergens and limitation of treatment efficacy greatly dampens successful management of asthma. The adverse events related to several drugs currently used, such as corticosteroids and ß-agonists, and the low rigorous adherence to preconized protocols likely compromises a more assertive therapy. Flavonoids represent a class of natural compounds with extraordinary antioxidant and anti-inflammatory properties, with their potential benefits already demonstrated for several diseases, including asthma. Advanced technology has been used in the pharmaceutical field to improve the efficacy and safety of drugs. Notably, there is also an increasing interest for the application of these techniques using natural products as active molecules. Flavones, flavonols, flavanones, and chalcones are examples of flavonoid compounds that were tested in controlled delivery systems for asthma treatment, and which achieved better treatment results in comparison to their free forms. This review aims to provide a comprehensive understanding of the development of novel controlled delivery systems to enhance the therapeutic potential of flavonoids as active molecules for asthma treatment.

Topical Administration of 15-Deoxy-Δ 12,14-Prostaglandin J2 Using a Nonionic Cream: Effect on UVB-Induced Skin Oxidative, Inflammatory, and Histopathological Modifications in Mice.

UVB radiation is certainly one of the most important environmental threats to which we are subjected to. This fact highlights the crucial protective role of the skin. However, the skin itself may not be capable of protecting against UVB depending on irradiation intensity and time of exposition. Sun blockers are used to protect our skin, but they fail to fully protect it against oxidative and inflammatory injuries initiated by UVB. To solve this issue, topical administration of active molecules is an option. 15-Deoxy-Δ 12,14-prostaglandin J2 (15d-PGJ2) is an arachidonic acid-derived lipid with proresolution and anti-inflammatory actions. However, as far as we are aware, there is no evidence of its therapeutic use in a topical formulation to treat the deleterious events initiated by UVB, which was the aim of the present study. We used a nonionic cream to vehiculate 15d-PGJ2 (30, 90, and 300 ng/mouse) (TFcPGJ2) in the skin of hairless mice. UVB increased skin edema, myeloperoxidase activity, metalloproteinase-9 activity, lipid peroxidation, superoxide anion production, gp91phox and COX-2 mRNA expression, cytokine production, sunburn and mast cells, thickening of the epidermis, and collagen degradation. UVB also diminished skin ability to reduce iron and scavenge free radicals, reduced glutathione (GSH), sulfhydryl proteins, and catalase activity. TFcPGJ2 inhibited all these pathological alterations in the skin caused by UVB. No activity was observed with the unloaded topical formulation. The protective outcome of TFcPGJ2 indicates it is a promising therapeutic approach against cutaneous inflammatory and oxidative pathological alterations.

Protection against UVB deleterious skin effects in a mouse model: effect of a topical emulsion containing Cordia verbenacea extract.

Cordia verbenacea DC (Boraginaceae) is a flowering shrub found along the Brazilian Atlantic Forest, Brazilian coast, and low areas of the Amazon. The crude extract of its leaves is widely used in Brazilian folk medicine as an anti-inflammatory, both topically and orally. The aim of this study is to evaluate the activity of C. verbenacea ethanolic leaves extract (CVE) against UVB-triggered cutaneous inflammation and oxidative damage in hairless mice. CVE treatment recovered cutaneous antioxidant capacity demonstrated by scavenging ABTS+ free radical and iron-reducing antioxidant potential evaluated by FRAP. CVE also controlled the following UV-triggered events in the skin: reduced glutathione (GSH) depletion, catalase activity decrease, and superoxide anion (O⋅-) build-up. Furthermore, mice treated with CVE exhibited less inflammation, shown by the reduction in COX-2 expression, TNF-α, IL-1ß, IL-6, edema, and neutrophil infiltration. CVE also regulated epidermal thickening and sunburn cells, reduced dermal mast cells, and preserved collagen integrity. The best results were obtained using 5% CVE-added emulsion. The present data demonstrate that topical administration of CVE presents photochemoprotective activity in a mouse model of UVB inflammation and oxidative stress. Because of the intricate network linking inflammation, oxidative stress, and skin cancer, these results also indicate the importance of further studies elucidating a possible role of C. verbenacea in the prevention of UVB-induced skin cancer and evaluating a potential synergy between CVE and sunscreens in topical products against UVB damaging effects to the skin.

A topical formulation containing quercetin-loaded microcapsules protects against oxidative and inflammatory skin alterations triggered by UVB irradiation: enhancement of activity by microencapsulation.

Ultraviolet B (UVB) irradiation causes free radical production, increase inflammation and oxidative stress, thus, supporting the use of antioxidants by topical administration as therapeutic approaches. Quercetin (QC) is a flavonoid with antioxidant activity, however, high liposolubility makes it difficult to remain in the viable skin layer. Thus, this study evaluated whether microencapsulation of QC would enhance its activity in comparison with the same dose of free QC (non-active dose) and unloaded-microcapsules added in formulation for topical administration in a mouse model of UVB irradiation targeting the skin. Topical formulation containing Quercetin-loaded microcapsules (TFcQCMC) presents physico-chemical (colour, consistence, phase separation and pH) and functional antioxidant stability at 4 °C, room temperature and 40 °C for 6 months. TFcQCMC inhibited the UVB-triggered depletion of antioxidants observed by GSH (reduced glutathione), ability to reduce iron, ability to scavenge 2,2'-azinobis radical and catalase activity. TFcQCMC also inhibited markers of oxidation (lipid hydroperoxides and superoxide anion production). Concerning inflammation, TFcQCMC reduced the production of inflammatory cytokines, matrix metalloproteinase-9 activity, skin edoema, collagen fibre damage, myeloperoxidase activity/neutrophil recruitment, mast cell and sunburn cell counts. The pharmacological activity of TFcQCMC was not shared by the same pharmaceutical form containing the same dose of free QC or unloaded control microcapsules.

Protective effect of oral treatment with Cordia verbenacea extract against UVB irradiation deleterious effects in the skin of hairless mouse.

Photochemoprotection of the skin can be achieved by inhibiting inflammation and oxidative stress, which we tested using Cordia verbenacea extract, a medicinal plant known for its rich content of antioxidant molecules and anti-inflammatory activity. In vitro antioxidant evaluation of Cordia verbenacea leaves ethanolic extract (CVE) presented the following results: ferric reducing antioxidant power (886.32 µM equivalent of Trolox/g extract); IC50 of 19.128 µg/ml for scavenging 2,2-diphenyl-1-picrylhydrazyl; IC50 of 12.48 µg/mL for scavenging 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid); decrease of hydroperoxides from linoleic acid (IC50 of 10.20 µg/mL); inhibition of thiobarbituric acid reactive substances (IC50 8.90 µg/mL); iron-chelating ability in bathophenanthroline iron assay (IC50 47.35 µg/mL); chemiluminescence triggered by free radicals in the H2O2/horseradish peroxidase/luminol (IC50 0.286 µg/mL) and xanthine/xanthine oxidase/luminol (IC50 0.42 µg/mL) methods. CVE (10-100 mg per kg, 30 min before and immediately after UVB exposure) treatment was performed by gavage in hairless mice. CVE inhibited skin edema, neutrophil infiltration, and overproduction of MMP-9; reduced levels of TNF-α, IL-1ß, and IL- 6; numbers of skin mast cells, epidermal thickening, number of epidermal apoptotic keratinocytes, and collagen degradation. CVE increased the skin's natural antioxidant defenses as observed by Nrf-2, NAD(P)H quinone oxidoreductase 1, and heme oxygenase 1 mRNA expression enhancement. Furthermore, CVE inhibited lipid peroxidation and superoxide anion production and recovered antioxidant reduced glutathione, catalase activity, and ROS scavenging capacity of the skin. Concluding, CVE downregulates the skin inflammatory and oxidative damages triggered by UVB, demonstrating its potentialities as a therapeutic approach.

The Lipoxin Receptor/FPR2 Agonist BML-111 Protects Mouse Skin Against Ultraviolet B Radiation.

Excessive exposure to UV, especially UVB, is the most important risk factor for skin cancer and premature skin aging. The identification of the specialized pro-resolving lipid mediators (SPMs) challenged the preexisting paradigm of how inflammation ends. Rather than a passive process, the resolution of inflammation relies on the active production of SPMs, such as Lipoxins (Lx), Maresins, protectins, and Resolvins. LXA4 is an SPM that exerts its action through ALX/FPR2 receptor. Stable ALX/FPR2 agonists are required because SPMs can be quickly metabolized within tissues near the site of formation. BML-111 is a commercially available synthetic ALX/FPR2 receptor agonist with analgesic, antioxidant, and anti-inflammatory properties. Based on that, we aimed to determine the effect of BML-111 in a model of UVB-induced skin inflammation in hairless mice. We demonstrated that BML-111 ameliorates the signs of UVB-induced skin inflammation by reducing neutrophil recruitment and mast cell activation. Reduction of these cells by BML-111 led to lower number of sunburn cells formation, decrease in epidermal thickness, collagen degradation, cytokine production (TNF-α, IL-1ß, IL-6, TGF, and IL-10), and oxidative stress (observed by an increase in total antioxidant capacity and Nrf2 signaling pathway), indicating that BML-111 might be a promising drug to treat skin disorders.

Analgesic activity and mechanism of action of a Beta vulgaris dye enriched in betalains in inflammatory models in mice.

Evidence demonstrates the pronounced anti-inflammatory activity of a beetroot (Beta vulgaris) dye enriched in betalains obtained using precipitation with ethanol. Herein, we expand upon our previous observations and demonstrate the analgesic and antioxidant effect of betalains. Betalains [10-1000 mg/kg; intraperitoneal route (i.p.)] diminished acetic acid- and PBQ-induced abdominal contortions, and the overt pain-like behaviour induced by complete Freund`s adjuvant (CFA) and formalin (intraplantar; i.pl.) injection. Moreover, betalains (100 mg/kg) administered by various routes [i.p. or subcutaneous (s.c.)] or as a post-treatment reduced carrageenin- or CFA-induced hyperalgesia. Mechanistically, betalains mitigated carrageenin-induced tumour necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, superoxide anion levels, and lipid peroxidation. Betalains also stopped the depletion of reduced glutathione (GSH) levels and ferric reducing ability produced by carrageenin, as well as upregulated Nrf2 and Ho1 transcript expression in the plantar tissue of mice. Furthermore, betalains showed hydroxyl radical, 2,2'-azino-di-(3-ethylbenzthiazoline-6-sulphonic acid) radical (ABTS+), and 2,2-diphenyl-1-picryl-hydrazyl radical (DPPH•) scavenging ability and iron-chelating activity (bathophenantroline assay), and inhibited iron-independent and iron-dependent lipid peroxidation (LPO) in vitro. Finally, betalains-treated bone marrow-derived macrophages exhibited lower levels of cytokines (TNF-α and IL-1ß), and superoxide anion levels and nuclear factor kappa B (NF-κB) activation following lipopolysaccharide (LPS) stimulation. Therefore, this betalain-rich dye extracted using a novel precipitation approach presents prominent analgesic effect in varied models of pain by mechanisms targeting cytokines and oxidative stress.

Treatment with maresin 1, a docosahexaenoic acid-derived pro-resolution lipid, protects skin from inflammation and oxidative stress caused by UVB irradiation.

Acute exposure to UVB irradiation causes skin inflammation and oxidative stress, and long-term exposure to UVB irradiation may lead to carcinogenesis. Our organism has endogenous mechanisms to actively limit inflammation. Maresin 1 (MaR1; 7R,14S-dihydroxy-docosa-4Z,8E,10E,12Z,16Z,19Z-hexaenoic acid) is a pro-resolution lipid mediator derived from the docosahexaenoic acid, which presents anti-inflammatory and pro-resolution effects. However, it remains to be determined if treatment with MaR1 can inhibit inflammatory and oxidative alterations in the skin triggered by UVB. The treatment with MaR1 (0.1-10 ng/mice at -10 min relative to the UVB irradiation protocol) reduced UVB-induced skin edema, neutrophil recruitment (MPO; myeloperoxidase activity, and migration of LysM-eGFP+ cells), cytokine production, matrix metalloproteinase-9 activity, keratinocyte apoptosis, epidermal thickening, mast cells counts and degradation of skin collagen in hairless mice. UVB irradiation caused a decrease of GSH (reduced glutathione) levels, activity of the enzyme catalase, ferric reducing ability (FRAP), and ABTS radical scavenging capacity as well as induced lipid hydroperoxide, superoxide anion production, and gp91phox mRNA expression. These parameters that indicate oxidative stress were inhibited by MaR1 treatment. Therefore, these data suggest MaR1 as a promising pharmacological tool in controlling the deleterious effects related to UVB irradiation.

The Lipid Mediator Resolvin D1 Reduces the Skin Inflammation and Oxidative Stress Induced by UV Irradiation in Hairless Mice.

UV irradiation-induced oxidative stress and inflammation contribute to the development of skin diseases. Therefore, targeting oxidative stress and inflammation might contribute to reduce skin diseases. Resolvin D1 (RvD1) is a bioactive metabolite generated during inflammation to actively orchestrate the resolution of inflammation. However, the therapeutic potential of RvD1 in UVB skin inflammation remains undetermined, which was, therefore, the aim of the present study. The intraperitoneal treatment with RvD1 (3-100 ng/mouse) reduced UVB irradiation-induced skin edema, myeloperoxidase activity, matrix metalloproteinase 9 activity, and reduced glutathione depletion with consistent effects observed with the dose of 30 ng/mouse, which was selected to the following experiments. RvD1 inhibited UVB reduction of catalase activity, and hydroperoxide formation, superoxide anion production, and gp91phox mRNA expression. RvD1 also increased the Nrf2 and its downstream targets NQO1 and HO-1 mRNA expression. Regarding cytokines, RvD1 inhibited UVB-induced production of IL-1ß, IL-6, IL-33, TNF-α, TGF-ß, and IL-10. These immuno-biochemical alterations by RvD1 treatment had as consequence the reduction of UVB-induced epidermal thickness, sunburn and mast cell counts, and collagen degradation. Therefore, RvD1 inhibited UVB-induced skin oxidative stress and inflammation, rendering this resolving lipid mediator as a promising therapeutic agent.

Topical emulsion containing pyrrolidine dithiocarbamate: effectiveness against ultraviolet B irradiation-induced injury of hairless mouse skin.

OBJECTIVES: To evaluate the effects of a topical emulsion containing pyrrolidine dithiocarbamate (PDTC) (EcPDTC) in skin oxidative stress and inflammation triggered by ultraviolet B (UVB) irradiation (dose of 4.14 J/cm2 ). METHODS: Hairless mouse received treatment with 0.5 g of EcPDTC or control emulsion (CTRLE) on the dorsal surface skin 12 h, 6 h and 5 min before and 6 h after the irradiation. Oxidative stress was evaluated by ferric reducing antioxidant power (FRAP), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS) scavenging capacity, reduced glutathione quantitation, catalase activity, superoxide anion production and lipid peroxidation products. Inflammation parameters were as follows: skin oedema, myeloperoxidase activity (neutrophil marker), matrix metalloproteinase-9 activity, collagen fibre damage, mast cell and sunburn cell counts, and cytokine production. KEY FINDINGS: Topical treatment with EcPDTC protected from UVB-induced skin injury by maintaining the antioxidant capacity levels similar to non-irradiated control group. Furthermore, EcPDTC inhibited UVB irradiation-induced superoxide anion production, lipid peroxidation and reduced skin inflammation by inhibiting skin oedema, neutrophil recruitment, metalloproteinase-9 activity, collagen fibre damage, mast cell and sunburn cell counts, and cytokine (TNF-α and IL-1ß) production. CONCLUSIONS: Topical treatment with EcPDTC improves antioxidant systems and inhibits inflammation, protecting the skin from the damaging effects of UVB irradiation.

Optimization of ultrasound-assisted extraction of grape-seed oil to enhance process yield and minimize free radical formation.

BACKGROUND: Grape seeds are a relatively abundant source of oil and bioactive compounds. To use this byproduct, the current work aimed to optimize the ultrasound-assisted extraction (UAE) of grape-seed oil to obtain greater process yield and minimize free radical formation in the oil. RESULTS: The optimal condition was 15 °C with an ultrasonic wave amplitude of 42 µm, leading to a process yield of 82.9% and content of free radicals of 14.7 × 1017 kg-1 and 3.4 × 1018 kg-1 for samples stored for 7 and 30 days, respectively. No significant differences in fatty acid composition and acidity and iodine values were observed between samples. The oil obtained by ultrasound had greater phenolic compound content and antioxidant activity by ferric reduction than the control sample (without ultrasound application). However, higher content of free radicals and peroxide value was observed. CONCLUSION: Sonication improved extraction yield when compared to the process without ultrasound application. Moreover, UAE favored the extraction of phenolic compounds. As it enhanced process yield with the minimum formation of free radicals, UAE is a promising oil-extraction technology. © 2018 Society of Chemical Industry.

Quercetin attenuates zymosan-induced arthritis in mice.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by articular lesions, recruitment of inflammatory cells and increased levels of pro-inflammatory cytokine. The intra-articular administration of zymosan is an experimental model that promotes inflammatory parameters resembling RA. Therefore, this model was used to investigate the efficacy of quercetin as a treatment of articular inflammation. Treatment with quercetin dose-dependently reduced zymosan-induced hyperalgesia, articular edema and the recruitment of neutrophils to the knee joint cavity. Histological analysis confirmed that quercetin inhibited zymosan-induced arthritis. The treatment with quercetin also inhibited zymosan-induced depletion of reduced glutathione (GSH) levels, TNFα and IL-1ß production, and gp91phox, prepro-endothelin-1 (preproET-1), and cyclooxygenase-2 mRNA expression. These molecular effects of quercetin were related to the inhibition of the nuclear factor kappa-B and induction of Nuclear factor erythroid 2- related factor (Nrf2)/home oxygenase (HO-1) pathway. Thus, quercetin exerted anti-inflammatory, analgesic and antioxidant effects in experimental arthritis, suggesting quercetin is a possible candidate for arthritis treatment.

trans-Chalcone, a flavonoid precursor, inhibits UV-induced skin inflammation and oxidative stress in mice by targeting NADPH oxidase and cytokine production.

trans-Chalcone is a plant flavonoid precursor, which lacks broad investigation on its biological activity in inflammatory processes. In the present study, anti-inflammatory and antioxidant mechanisms of systemic administration with trans-chalcone, a flavonoid precursor, on ultraviolet (UV) irradiation-induced skin inflammation and oxidative stress in hairless mice were investigated by the following parameters: skin edema, myeloperoxidase activity (neutrophil marker), matrix metalloproteinase-9 activity, reduced glutathione levels, catalase activity, lipid peroxidation products, superoxide anion production, gp91phox (NADPH oxidase subunit) mRNA expression by quantitative PCR and cytokine production by ELISA. Systemic treatment with trans-chalcone inhibited skin inflammation by reducing skin edema and neutrophil recruitment, and also inhibited matrix metalloproteinase-9 activity. trans-Chalcone also inhibited oxidative stress, gp91phox mRNA expression, and the production of a wide range of pro-inflammatory cytokines, while it did not affect anti-inflammatory cytokines induced by UV irradiation. However, trans-chalcone did not prevent oxidative stress in vitro, suggesting that its in vivo effect is more related to anti-inflammatory properties rather than a direct antioxidant effect. In conclusion, treatment with trans-chalcone inhibited UV-induced skin inflammation resulting in oxidative stress inhibition in vivo. Therefore, systemic supplementation with this compound may represent an important therapeutic approach in inflammatory skin diseases induced by UV irradiation.