RESUMEN
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.
Asunto(s)
Chalcona/farmacología , Citocinas/biosíntesis , Inflamación/prevención & control , NADPH Oxidasas/metabolismo , Estrés Oxidativo/efectos de los fármacos , Piel/efectos de los fármacos , Piel/efectos de la radiación , Rayos Ultravioleta , Animales , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/farmacología , Chalcona/química , Relación Dosis-Respuesta a Droga , Edema/tratamiento farmacológico , Ensayo de Inmunoadsorción Enzimática , Inflamación/metabolismo , Masculino , Ratones , Ratones Pelados , Estructura Molecular , Estrés Oxidativo/efectos de la radiación , Piel/metabolismo , Piel/patología , Relación Estructura-ActividadRESUMEN
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-1ß, 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.
Asunto(s)
Chalconas/administración & dosificación , Hesperidina/análogos & derivados , Inflamación/prevención & control , Estrés Oxidativo/efectos de los fármacos , Piel/efectos de los fármacos , Rayos Ultravioleta , Administración Tópica , Animales , Chalconas/farmacología , Citocinas/biosíntesis , Hemo-Oxigenasa 1/genética , Hesperidina/administración & dosificación , Hesperidina/farmacología , Inflamación/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Ratones , Ratones Pelados , NADPH Oxidasa 2 , NADPH Oxidasas/genética , NADPH Oxidasas/metabolismo , Factor 2 Relacionado con NF-E2/genética , ARN Mensajero/genética , Piel/metabolismo , Superóxidos/metabolismoRESUMEN
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-1ß, 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.
Asunto(s)
Antioxidantes/farmacología , Edema/prevención & control , Flavanonas/farmacología , Estrés Oxidativo/efectos de los fármacos , Piel/efectos de los fármacos , Rayos Ultravioleta/efectos adversos , Administración Cutánea , Animales , Benzotiazoles/antagonistas & inhibidores , Benzotiazoles/metabolismo , Catalasa/genética , Catalasa/metabolismo , Edema/etiología , Edema/genética , Edema/patología , Expresión Génica/efectos de los fármacos , Glutatión/metabolismo , Glutatión Peroxidasa/genética , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/genética , Glutatión Reductasa/metabolismo , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Radical Hidroxilo/antagonistas & inhibidores , Radical Hidroxilo/metabolismo , Inflamación , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Ratones , Ratones Pelados , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Piel/metabolismo , Piel/patología , Piel/efectos de la radiación , Ácidos Sulfónicos/antagonistas & inhibidores , Ácidos Sulfónicos/metabolismo , Superóxidos/antagonistas & inhibidores , Superóxidos/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Glutatión Peroxidasa GPX1RESUMEN
Ultraviolet B (UVB) irradiation may cause inflammation- and oxidative-stress-dependent skin cancer and premature aging. Naringenin (1) has been reported to have anti-inflammatory and antioxidant properties, but its effects and mechanisms on UVB irradiation-induced inflammation and oxidative stress are still not known. Thus, the present study aimed to investigate the potential of naringenin to mitigate UVB irradiation-induced inflammation and oxidative damage in the skin of hairless mice. Skin edema, myeloperoxidase (neutrophil marker) and matrix metalloproteinase-9 (MMP-9) activity, and cytokine production were measured after UVB irradiation. Oxidative stress was evaluated by 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS) scavenging ability, ferric reducing antioxidant power (FRAP), reduced glutathione levels, catalase activity, lipid peroxidation products, superoxide anion production, and gp91phox (NADPH oxidase subunit) mRNA expression by quantitative PCR. The intraperitoneal treatment with naringenin reduced skin inflammation by inhibiting skin edema, neutrophil recruitment, MMP-9 activity, and pro-inflammatory (TNF-α, IFN-γ, IL-1ß, IL-4, IL-5, IL-6, IL-12, IL-13, IL-17, IL-22, and IL-23) and anti-inflammatory (TGF-ß and IL-10) cytokines. Naringenin also inhibited oxidative stress by reducing superoxide anion production and the mRNA expression of gp91phox. Therefore, naringenin inhibits UVB irradiation-induced skin damage and may be a promising therapeutic approach to control skin disease.
Asunto(s)
Flavanonas/farmacología , Estrés Oxidativo/efectos de los fármacos , Piel/efectos de los fármacos , Rayos Ultravioleta , Animales , Antioxidantes/farmacología , Benzotiazoles/farmacología , Flavanonas/química , Glutatión/metabolismo , Inflamación/metabolismo , Interleucina-10/metabolismo , Interleucina-12/farmacología , Interleucina-17 , Interleucina-4 , Interleucina-6/metabolismo , Interleucinas , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones , Ratones Pelados , Estructura Molecular , Estrés Oxidativo/efectos de la radiación , Piel/efectos de la radiación , Ácidos Sulfónicos/farmacología , Factor de Crecimiento Transformador beta/farmacología , Factor de Necrosis Tumoral alfa/farmacología , Interleucina-22RESUMEN
Hesperidin methyl chalcone (HMC) is a safe flavonoid used to treat chronic venous diseases, but its effects and mechanisms on UVB irradiation-induced inflammation and oxidative stress have never been described in vivo. Thus, the purpose of this study was to evaluate the effects of systemic administration of HMC in skin oxidative stress and inflammation induced by UVB irradiation. To induce skin damage, hairless mice were exposed to an acute UVB irradiation dose of 4.14 J/cm(2), and the dorsal skin samples were collected to evaluate oxidative stress and inflammatory response. The intraperitoneal treatment with HMC at the dose of 300 mg/kg inhibited UVB irradiation-induced skin edema, neutrophil recruitment, and matrix metalloproteinase-9 activity. HMC also protected the skin from UVB irradiation-induced oxidative stress by maintaining ferric reducing antioxidant power (FRAP), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS) scavenging ability and antioxidant levels (reduced glutathione and catalase). Corroborating, HMC inhibited UVB irradiation-induced superoxide anion generation and gp91phox (NADPH oxidase subunit) mRNA expression. Furthermore, the antioxidant effect of HMC resulted in lower production of inflammatory mediators, including lipid hydroperoxides and a wide range of cytokines. Taken together, these results unveil a novel applicability of HMC in the treatment of UVB irradiation-induced skin inflammation and oxidative stress.