Fucoxanthin-Containing Cream Prevents Epidermal Hyperplasia and UVB-Induced Skin Erythema in Mice

Abstract

Microalgae represent a source of bio-active compounds such as carotenoids with potent anti-inflammatory and antioxidant properties. We aimed to investigate the effects of fucoxanthin (FX) in both in vitro and in vivo skin models. Firstly, its anti-inflammatory activity was evaluated in LPS-stimulated THP-1 macrophages and TNF-α-stimulated HaCaT keratinocytes, and its antioxidant activity in UVB-irradiated HaCaT cells. Next, in vitro and ex vivo permeation studies were developed to determine the most suitable formulation for in vivo FX topical application. Then, we evaluated the effects of a FX-containing cream on TPA-induced epidermal hyperplasia in mice, as well as on UVB-induced acute erythema in hairless mice. Our results confirmed the in vitro reduction of TNF-α, IL-6, ROS and LDH production. Since the permeation results showed that cream was the most favourable vehicle, FX-cream was elaborated. This formulation effectively ameliorated TPA-induced hyperplasia, by reducing skin edema, epidermal thickness, MPO activity and COX-2 expression. Moreover, FX-cream reduced UVB-induced erythema through down-regulation of COX-2 and iNOS as well as up-regulation of HO-1 protein via Nrf-2 pathway. In conclusion, FX, administered in a topical formulation, could be a novel natural adjuvant for preventing exacerbations associated with skin inflammatory pathologies as well as protecting skin against UV radiation.

Fucoxanthin for Topical Administration, a Phototoxic vs. Photoprotective Potential in a Tiered Strategy Assessed by In Vitro Methods

“…Our study corroborates those reported before [48], which employed the HaCat cell line and hairless mice to study the UVB protective effects of commercial all-trans-fucoxanthin (Sigma). They observed that fucoxanthin has anti-inflammatory activity by downregulating Cyclooxygenase-2 (COX-2) expression after UVB irradiation (mice) and a photoprotective effect against oxidative stress that is caused by UVB exposure via an increase of nuclear factor E2-related factor 2 (Nrf2) expression.…”

“…They observed that fucoxanthin has anti-inflammatory activity by downregulating Cyclooxygenase-2 (COX-2) expression after UVB irradiation (mice) and a photoprotective effect against oxidative stress that is caused by UVB exposure via an increase of nuclear factor E2-related factor 2 (Nrf2) expression. Thus, although Rodríguez-Luna et al [48] obtained valuable information from hairless mice, it is well known that human adverse events cannot always be detected in animals, due to inherent genetic and physiological differences between species and that skin model constructed with human cells and physiologic relevant microarchitecture contributes to the better prediction of human effects. In the previous study of our group, commercial fucoxanthin at the same concentration, presented an absence of irritation, absence of morphological changes in the histology, and no significant dysregulation on homeostasis, metabolism, and in the inflammatory genes studied after following the OECD protocol for skin irritation [49].…”

Epigenetic treatment of dermatologic disorders

“…Nrf2‐activating compounds are becoming staple ingredients in topically applied skin‐conditioning creams and other formulations that mitigate skin damage (Ahmed, ; Ben‐Nun, ; Braidy et al, ; Burke, ; Davinelli, Nielsen, & Scapagnini, ; Gorini et al, ; Huang, Wang, Yang, Chou, & Fang, ; Kocot, Kiełczykowska, Luchowska‐Kocot, Kurzepa, & Musik, ; Kunnumakkara et al, ; Lephart, ; Ríos, Giner, Marín, & Recio, ; Rodríguez‐Luna et al, ; Simitzis, ; Vega et al, , ; Vollmer et al, ; Yang et al, ; Yokota, Yahagi, & Masaki, ), promote skin repair (Bellot et al, ; Davinelli, Nielsen, & Scapagnini, ; Ferreira & Gomes, ; Kim et al, ; Yang et al, ), and enhance diabetic‐associated wound healing (Bellot et al, ; Ben‐Nun, ; Cuadrado et al, ; Ferreira & Gomes, ; Gorini et al, ; Huang et al, ; Kim et al, ; Kocot et al, ; Kunnumakkara et al, ; Panahi et al, ; Ríos et al, ; Sanchez, Lancel, Boulanger, & Neviere, ; Vega et al, ; Vega et al, ; Vollmer et al, ). With respect to the latter, almost a third of the world's population is considered to be overweight or obese (González‐Muniesa et al, ) and the percentage is rising to epidemic proportions (Blaszczak et al, ; Severin, Sabbahi, Mahmoud, Arena, & Phillips, ).…”

“…Nrf2-activating compounds are becoming staple ingredients in topically applied skin-conditioning creams and other formulations that mitigate skin damage (Ahmed, 2019;Ben-Nun, 2018;Braidy et al, 2019;Burke, 2018;Davinelli, Nielsen, & Scapagnini, 2018;Gorini et al, 2019;Huang, Wang, Yang, Chou, & Fang, 2018;Kocot, Kiełczykowska, Luchowska-Kocot, Kurzepa, & Musik, 2018;Kunnumakkara et al, 2017;Lephart, 2018;Ríos, Giner, Marín, & Recio, 2018;Rodríguez-Luna et al, 2018;Simitzis, 2018;Vega et al, 2017Vega et al, , 2018Vollmer et al, 2018;Yokota, Yahagi, & Masaki, 2018), promote skin repair (Bellot et al, 2019;Davinelli, Nielsen, & Scapagnini, 2018;Ferreira & Gomes, 2018;, and enhance diabeticassociated wound healing (Bellot et al, 2019;Ben-Nun, 2018;Cuadrado et al, 2019;Ferreira & Gomes, 2018;Gorini et al, 2019;Huang et al, 2018;Kocot et al, 2018;Kunnumakkara et al, 2017;Panahi et al, 2019;Ríos et al, 2018;Sanchez, Lancel, Boulanger, & Neviere, 2018;Vega et al, 2017;Vega et al, 2018;Vollmer et al, 2018).…”

Xanthigen® reduces lipid deposition and improves stress resistance in Caenorhabditis elegans

“…The effects of Xanthigen® are explained by the combination of properties of these two components. Many studies have shown anti-oxidant, anti-inflammatory, and anticancer activities of fucoxanthin 8,9 . In addition, it has been shown that fucoxanthin stimulated lipolysis and inhibited lipogenesis by increasing Uncoupling Protein 1 (UCP1) expression in both white and brown adipose tissue 10 .…”