interleukin-8 and Hypopigmentation

UV radiation from the sun is the most common environmental stressor to damage the skin. It is now well established that photodamaged skin manifests signs of mild but chronic inflammation, termed as "inflammaging." Thus, there is an urgent need for anti-inflammatory regimes that can limit the damage caused by inflammation.. This study aimed to evaluate the possible palliative effects of a new topical nanoemulsion formulation containing tocotrienol-rich fraction (TRF) on UV-induced inflammation (erythema) of human skin.. An in vitro model was used to demonstrate the ability of TRF to alleviate photodamage via attenuation of UV-induced oxidative stress and inflammation. Two ex vivo models (skin antioxidative potential and radical sun protection factor) were used to determine the efficacy of different formulations of TRF on the skin. A UV-induced erythema protection test in 20 subjects was conducted.. In vitro studies involving HaCaT keratinocytes revealed that TRF possesses marked anti-inflammatory properties, as indicated by the attenuation of UV-induced upregulation of pro-inflammatory cytokines. A 1% TRF formulation was found to be more effective in enhancing the endogenous antioxidative protection of skin compared to 1% TRF in medium chain triglycerides because of its higher penetration kinetic profile. The clinical study showed that formulated TRF was effective in reducing skin redness after UV irradiation as early as after 6 hours of application. A significant depigmentation was also observed in TRF treatment subjects.. TRF may serve as an anti-inflammatory compound that is safe to be applied daily to protect the skin from UV-induced inflammaging.

Topics: Adult; Animals; Antioxidants; Cell Line; Cell Survival; Cyclooxygenase 2; Deoxyadenosines; Emulsions; Erythema; Humans; Hypopigmentation; Interleukin-6; Interleukin-8; Keratinocytes; Middle Aged; Nanostructures; Oxidative Stress; Radiodermatitis; Reactive Oxygen Species; Swine; Tocotrienols; Ultraviolet Rays

Rhododendrol, an inhibitor of melanin synthesis developed for lightening/whitening cosmetics, was recently reported to induce a depigmentary disorder principally at the sites of repeated chemical contact. Rhododendrol competitively inhibited mushroom tyrosinase and served as a good substrate, while it also showed cytotoxicity against cultured human melanocytes at high concentrations sufficient for inhibiting tyrosinase. The cytotoxicity was abolished by phenylthiourea, a chelator of the copper ions at the active site, and by specific knockdown of tyrosinase with siRNA. Hence, the cytotoxicity appeared to be triggered by the enzymatic conversion of rhododendrol to active product(s). No reactive oxygen species were detected in the treated melanocytes, but up-regulation of the CCAAT-enhancer-binding protein homologous protein gene responsible for apoptosis and/or autophagy and caspase-3 activation were found to be tyrosinase dependent. These results suggest that a tyrosinase-dependent accumulation of ER stress and/or activation of the apoptotic pathway may contribute to the melanocyte cytotoxicity.

Topics: Agaricales; Apoptosis; Butanols; Caspase 3; Catalytic Domain; Cell Survival; Cells, Cultured; Chelating Agents; Copper; Endoplasmic Reticulum Stress; Enhancer Elements, Genetic; Enzyme-Linked Immunosorbent Assay; Gene Expression Profiling; Gene Expression Regulation; Humans; Hypopigmentation; Inhibitory Concentration 50; Interleukin-8; Melanocytes; Monophenol Monooxygenase; Phenylthiourea; Pigmentation; Reactive Oxygen Species; RNA, Small Interfering; Skin Lightening Preparations; Up-Regulation; Vitiligo