Fernblock® Upregulates NRF2 Antioxidant Pathway and Protects Keratinocytes from PM2.5-Induced Xenotoxic Stress.

Pablo Delgado-Wicke,Salvador González,Yoichi Honma,Azahara Rodríguez-Luna,Toshiaki Kume,María Gutierrez,Silvia Lorrio,Ángeles Juarranz,Yoshifumi Ikeyama

doi:10.1155/2020/2908108

Abstract

Humans in modern industrial and postindustrial societies face sustained challenges from environmental pollutants, which can trigger tissue damage from xenotoxic stress through different mechanisms. Thus, the identification and characterization of compounds capable of conferring antioxidant effects and protection against these xenotoxins are warranted. Here, we report that the natural extract of Polypodium leucotomos named Fernblock®, known to reduce aging and oxidative stress induced by solar radiations, upregulates the NRF2 transcription factor and its downstream antioxidant targets, and this correlates with its ability to reduce inflammation, melanogenesis, and general cell damage in cultured keratinocytes upon exposure to an experimental model of fine pollutant particles (PM2.5). Our results provide evidence for a specific molecular mechanism underpinning the protective activity of Fernblock® against environmental pollutants and potentially other sources of oxidative stress and damage-induced aging.

Highlights

Air pollution is a growing challenge to public health worldwide and constitutes an emerging focus of research and surveillance for the World Health Organization [1]
Fernblock® induced the reporter in a concentration-dependent manner, suggesting that it is capable of upregulating this protective pathway in cells (Figure 1(c)). We investigated whether this effect occurs in keratinocytes and whether it is associated with specific protection from exposure to UVB radiation. qRT-PCR assessment of mRNA levels for several bona fide targets of Nuclear factor erythroid 2-related factor 2 (NRF2) (CAT, glutathione peroxidase (GPX) 1 and 4, HO-1, and NAD(P)H Quinone Dehydrogenase 1 (NQO1)) revealed that Fernblock® induces the transcription of all these genes in human keratinocytes in a concentration-dependent manner (Figures 1(d)–1(h))
Cellular mechanisms contrasting environmental pollutants include the aryl hydrocarbon receptor (AhR) pathway, which positively regulates cyp450 detoxification systems and artemin [24]; the metal regulatory transcription factor-1 (MTF-1), which promotes the expression of antioxidant genes and metallothioneins in response to accumulation of heavy metals such as silver, cadmium, copper, or zinc [25]; and the conserved NRF2 pathway, which determines broad antioxidant and detoxifying transcriptional processes in response to different

Summary

Introduction

Air pollution is a growing challenge to public health worldwide and constitutes an emerging focus of research and surveillance for the World Health Organization [1]. Because of the role of the skin as a primary barrier against external sources of tissue damage, continuous exposure to these pollutants has a substantial negative impact on this organ and is precursory of premature skin aging, pigmentation, acne disorders, and psoriasis exacerbation, among others [2]. Air pollution, solar radiation, and tobacco smoke constitute extrinsic skin-aging factors, leading to ROS production and the subsequent activation of oxidative stress responses. Skin antioxidant defense responses are effective against these exogenous sources of damage; chronic exposure, aging, or several. Oxidative Medicine and Cellular Longevity concomitant pathologies can lead to decreased activation and increased oxidative damage, accelerating skin aging and skin cancer [6]. Understanding mechanisms by which tissues confront these sources of xenotoxic stress and potential pharmacological opportunities to leverage on them are warranted

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Conclusion