4-Hexyl-1,3-Phenylenediol, A Nuclear Factor-Kappa B Inhibitor, Improves Photodamaged Skin And Clinical Signs Of Ageing In A Double-Blinded, Randomized Controlled Trial

Background The nuclear factor-kappa B (NF-kappa B) pathway is a key mediator of inflammation; however, few studies have examined the direct effects of NF-kappa B inhibition on the skin.Objectives To investigate NF-kappa B activity in cultured human fibroblasts and to investigate the effects of 4-hexyl-1,3-phenylenediol (an NF-kappa B inhibitor) on elastin and collagen gene expression in vitro and on the clinical appearance of photodamaged skin.Methods The amount and activity of NF-kappa B in human fibroblasts obtained from donors (17-78 years old) was measured after transfection with a NF-kappa B reporter and a luciferase promoter system. The expression of extracellular matrix (ECM) genes was determined using quantitative polymerase chain reaction. Women with moderate skin photodamage were randomized to daily treatment with a topical lotion containing 4-hexyl-1,3-phenylenediol (n = 30) or vehicle (n = 29) for 8 weeks, with clinical assessments at baseline and weeks 2, 4 and 8.Results Fibroblasts obtained from donors older than 50 years had higher NF-kappa B activity compared with cells from younger donors; inhibition of the NF-kappa B pathway with 4-hexyl-1,3-phenylenediol enhanced the expression of ECM genes. In women, treatment for 8 weeks with 4-hexyl-1,3-phenylenediol significantly improved crow's feet fine lines, cheek wrinkles, age spots, mottled pigmentation and radiance compared with both the vehicle and baseline. Furthermore, treatment with 4-hexyl-1,3-phenylenediol resulted in a twofold greater clinical improvement in overall photodamage compared with the vehicle group.Conclusions Inhibition of the proinflammatory NF-kappa B pathway resulted in increased expression of ECM proteins in vitro and significant clinical improvement in photodamaged skin.