Topical Formulation Containing Naringenin: Efficacy against Ultraviolet B Irradiation-Induced Skin Inflammation and Oxidative Stress in Mice

PLoS One. 2016 Jan 7;11(1):e0146296. doi: 10.1371/journal.pone.0146296. eCollection 2016.

Abstract

Naringenin (NGN) exhibits anti-inflammatory and antioxidant activities, but it remains undetermined its topical actions against ultraviolet B (UVB)-induced inflammation and oxidative stress in vivo. The purpose of this study was to evaluate the physicochemical and functional antioxidant stability of NGN containing formulations, and the effects of selected NGN containing formulation on UVB irradiation-induced skin inflammation and oxidative damage in hairless mice. NGN presented ferric reducing power, ability to scavenge 2,2'-azinobis (3-ethylbenzothiazoline- 6-sulfonic acid) (ABTS) and hydroxyl radical, and inhibited iron-independent and dependent lipid peroxidation. Among the three formulations containing NGN, only the F3 kept its physicochemical and functional stability over 180 days. Topical application of F3 in mice protected from UVB-induced skin damage by inhibiting edema and cytokine production (TNF-α, IL-1β, IL-6, and IL-10). Furthermore, F3 inhibited superoxide anion and lipid hydroperoxides production and maintained ferric reducing and ABTS scavenging abilities, catalase activity, and reduced glutathione levels. In addition, F3 maintained mRNA expression of cellular antioxidants glutathione peroxidase 1, glutathione reductase and transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2), and induced mRNA expression of heme oxygenase-1. In conclusion, a formulation containing NGN may be a promising approach to protecting the skin from the deleterious effects of UVB irradiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Antioxidants / pharmacology*
  • Benzothiazoles / antagonists & inhibitors
  • Benzothiazoles / metabolism
  • Catalase / genetics
  • Catalase / metabolism
  • Edema / etiology
  • Edema / genetics
  • Edema / pathology
  • Edema / prevention & control*
  • Flavanones / pharmacology*
  • Gene Expression / drug effects
  • Glutathione / metabolism
  • Glutathione Peroxidase / genetics
  • Glutathione Peroxidase / metabolism
  • Glutathione Peroxidase GPX1
  • Glutathione Reductase / genetics
  • Glutathione Reductase / metabolism
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism
  • Hydroxyl Radical / antagonists & inhibitors
  • Hydroxyl Radical / metabolism
  • Inflammation
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Lipid Peroxidation / drug effects
  • Mice
  • Mice, Hairless
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress / drug effects*
  • Skin / drug effects*
  • Skin / metabolism
  • Skin / pathology
  • Skin / radiation effects
  • Sulfonic Acids / antagonists & inhibitors
  • Sulfonic Acids / metabolism
  • Superoxides / antagonists & inhibitors
  • Superoxides / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Ultraviolet Rays / adverse effects*

Substances

  • Antioxidants
  • Benzothiazoles
  • Flavanones
  • IL10 protein, mouse
  • Interleukin-1beta
  • Interleukin-6
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Sulfonic Acids
  • Tumor Necrosis Factor-alpha
  • interleukin-6, mouse
  • Superoxides
  • Interleukin-10
  • 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid
  • Hydroxyl Radical
  • Catalase
  • Glutathione Peroxidase
  • Heme Oxygenase-1
  • Glutathione Reductase
  • Glutathione
  • naringenin
  • Glutathione Peroxidase GPX1
  • Gpx1 protein, mouse

Grants and funding

This work was supported by Brazilian grants from Coordenadoria de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Ministério da Ciência, Tecnologia e Inovação (MCTI)/Secretaria da Ciência, Tecnologia e Inovação (SETI)/Fundação Araucária, and Paraná State Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Farmacore Biotecnologia LTDA provided support in the form of salaries for authors [FTMCV], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.