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4‐Hexyl‐1,3‐phenylenediol, a nuclear factor‐κB inhibitor, improves photodamaged skin and clinical signs of ageing in a double‐blinded, randomized controlled trial
Author(s) -
Kaur S.,
Kizoulis M.,
Fantasia J.,
Oddos T.,
Bigot N.,
Galera P.,
TuckerSamaras S.,
Leyden J.J.,
Southall M.D.
Publication year - 2015
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.13747
Subject(s) - proinflammatory cytokine , extracellular matrix , medicine , microbiology and biotechnology , inflammation , chemistry , pharmacology , immunology , biology , biochemistry
Summary Background The nuclear factor‐κB ( NF ‐κB) pathway is a key mediator of inflammation; however, few studies have examined the direct effects of NF ‐κB inhibition on the skin. Objectives To investigate NF ‐κB activity in cultured human fibroblasts and to investigate the effects of 4‐hexyl‐1,3‐phenylenediol (an NF ‐κB inhibitor) on elastin and collagen gene expression in vitro and on the clinical appearance of photodamaged skin. Methods The amount and activity of NF ‐κB in human fibroblasts obtained from donors (17–78 years old) was measured after transfection with a NF ‐κB 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 ‐κB activity compared with cells from younger donors; inhibition of the NF ‐κB 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 ‐κB pathway resulted in increased expression of ECM proteins in vitro and significant clinical improvement in photodamaged skin.