title: Topical formulation containing hesperidin methyl chalcone inhibits skin oxidative stress and inflammation induced by ultraviolet B irradiation.
abstract: Skin exposure to ultraviolet B (UVB) irradiation has increased significantly in recent years due to ozone depletion, and it represents the main cause of many skin diseases. Hesperidin methyl chalcone (HMC) is a compound used to treat vascular diseases that has demonstrated anti-inflammatory activities in pre-clinical studies. Herein, we tested the antioxidant activity of HMC in cell free systems and the in vivo effects of a stable topical formulation containing HMC in a mouse model of skin oxidative stress and inflammation induced by UVB irradiation. HMC presented ferric reducing power, neutralized 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and hydroxyl free radicals, and inhibited lipid peroxidation. In hairless mice, a topical formulation containing HMC inhibited UVB irradiation-induced skin edema, depletion of antioxidant capacity (ferric and ABTS reducing abilities and catalase activity), lipid peroxidation, superoxide anion production and mRNA expression of gp91phox (nicotinamide adenine dinucleotide phosphate [NADPH] oxidase 2 sub-unity). In addition, HMC inhibited UVB irradiation-induced depletion of reduced glutathione levels by maintaining glutathione peroxidase-1 and glutathione reductase mRNA expression, prevented down-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA expression and increased heme oxygenase-1 mRNA expression. Finally, we demonstrated that topical application of the formulation containing HMC inhibited cytokine (TNF-α, IL-1β, IL-6, and IL-10) production induced by UVB irradiation. Therefore, this topical formulation containing HMC is a promising new therapeutic approach to protecting the skin from the deleterious effects of UVB irradiation.
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Estadual de Londrina, Avenida Robert Koch, 60, Hospital Universitário, 86039-440 Londrina, Paraná, Brazil. rubiacasa@yahoo.com.br.
authors.forename: Renata M
authors.initials: RM
authors.lastname: Martinez
authors.forename: Felipe A
authors.initials: FA
authors.lastname: Pinho-Ribeiro
authors.forename: Vinicius S
authors.initials: VS
authors.lastname: Steffen
authors.forename: Carla V
authors.initials: CV
authors.lastname: Caviglione
authors.forename: Danilo
authors.initials: D
authors.lastname: Pala
authors.forename: Marcela M
authors.initials: MM
authors.lastname: Baracat
authors.forename: Sandra R
authors.initials: SR
authors.lastname: Georgetti
authors.forename: Waldiceu A
authors.initials: WA
authors.lastname: Verri
authors.forename: Rubia
authors.initials: R
authors.lastname: Casagrande
mesh_terms: D000287:Administration, Topical; D000818:Animals; D047188:Chalcones / Q000008:administration & dosage* / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D051547:Heme Oxygenase-1 / Q000235:genetics; D006569:Hesperidin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008812:Mice, Hairless; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D047188:Chalcones; D016207:Cytokines; D008562:Membrane Glycoproteins; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D012333:RNA, Messenger; D013481:Superoxides; C033022:hesperidin methylchalcone; D006569:Hesperidin; D051547:Heme Oxygenase-1; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases