ABSTRACT
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.
Subject(s)
Anti-Inflammatory Agents/chemistry , Antioxidants/chemistry , Cordia/chemistry , Plant Extracts/chemistry , Plant Leaves/chemistry , Protective Agents/chemistry , Animals , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Cytokines/metabolism , Edema/metabolism , Female , Heme Oxygenase-1/metabolism , Humans , Hydrogen Peroxide/chemistry , Linoleic Acid/chemistry , Lipid Peroxidation , Mice, Hairless , NF-E2-Related Factor 2/metabolism , Oxidative Stress/drug effects , Oxidative Stress/radiation effects , Plant Extracts/pharmacology , Protective Agents/pharmacology , Quinone Reductases/metabolism , Skin/radiation effects , Superoxides/metabolism , Ultraviolet RaysABSTRACT
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.
