Diphlorethohydroxycarmalol Attenuates Fine Particulate Matter-Induced Subcellular Skin Dysfunction

Abstract

The skin, the largest organ in humans, is exposed to major sources of outdoor air pollution, such as fine particulate matter with a diameter ≤ 2.5 µm (PM2.5). Diphlorethohydroxycarmalol (DPHC), a marine-based compound, possesses multiple activities including antioxidant effects. In the present study, we evaluated the protective effect of DPHC on PM2.5-induced skin cell damage and elucidated the underlying mechanisms in vitro and in vivo. The results showed that DPHC blocked PM2.5-induced reactive oxygen species generation in human keratinocytes. In addition, DPHC protected cells against PM2.5-induced DNA damage, endoplasmic reticulum stress, and autophagy. HR-1 hairless mice exposed to PM2.5 showed lipid peroxidation, protein carbonylation, and increased epidermal height, which were inhibited by DPHC. Moreover, PM2.5 induced apoptosis and mitogen-activated protein kinase (MAPK) protein expression; however, these changes were attenuated by DPHC 5. MAPK inhibitors were used to elucidate the molecular mechanisms underlying these actions, and the results demonstrated that MAPK signaling pathway may play a key role in PM2.5-induced skin damage.

Protective Effect of Diphlorethohydroxycarmalol Isolated from Ishige okamurae Against Particulate Matter-Induced Skin Damage by Regulation of NF-κB, AP-1, and MAPKs Signaling Pathways In Vitro in Human Dermal Fibroblasts

“…The activated NF-κB subunits (p50 and p65) translated into the nucleus could induce the expression of pro-inflammatory cytokines and MMPs [34,41]. AP-1 could promote several MMPs expression, and it was activated by the phosphorylated MAPKs, which activate by ROS overproduction [34,37]. Thus, in the present study, the activated NF-κB, AP-1, and MAPKs were measured by Western blot assay.…”

“…Diphlorethohydroxycarmalol (DPHC, Figure 1), a phenolic compound derived from I. okamurae, which possesses the potential for skin protection [34][35][36]. Previous studies suggested that DPHC could effectively protect skins against epidermic damages induced by UVB irradiation and PM in human keratinocytes (HaCaT cells) [36,37]. In addition, the protective effect of DPHC on UVB-induced dermic damages in human dermal fibroblasts (HDF cells) has been investigated [34].…”

Seaweed Secondary Metabolites with Beneficial Health Effects: An Overview of Successes in In Vivo Studies and Clinical Trials

“…[46]. Diphlorethohydroxycarmalol 3 decreased the oxidative stress caused to the skin tissue of HR-1 hairless mice by fine particulate matter with a diameter ≤2.5 µm (PM 2.5 ), a major pollutant present in the atmosphere [44] (Table 1). Exposure to PM 2.5 caused lipid peroxidation and protein carbonylation, and increased epidermal height, which were inhibited by 3.…”

“…Exposure to PM 2.5 caused lipid peroxidation and protein carbonylation, and increased epidermal height, which were inhibited by 3. Moreover, PM 2.5 induced apoptosis and mitogen-activated protein kinase (MAPK) protein expression; however, these changes were attenuated by 3 [44].…”

“…In addition to the good results presented by phlorotannins in in vivo studies, which showed their high pharmaceutical potential, there were some studies [31,44] where there was no information about the actual amount of compound administered, which hindered their comparison with other studies, as well as the reproducibility of the results. Also, the majority of the referenced studies, particularly those using a murine model, had a small group of individuals per study group (4)(5)(6), which may not be very representative of the real effect of the compounds.…”