(-)-Loliolide Isolated from Sargassum horneri Suppressed Oxidative Stress and Inflammation by Activating Nrf2/HO-1 Signaling in IFN-γ/TNF-α-Stimulated HaCaT Keratinocytes.

Eui-Jeong Han,Dae-Sung Lee,Ilekuttige Priyan Shanura Fernando,Ginnae Ahn,Young-Heun Jee,You-Jin Jeon,Min-Jeong Seo,Hyun-Soo Kim,Areum Kim,Seo-Young Kim,Jun-Geon Je

doi:10.3390/antiox10060856

Abstract

The present study evaluated the effects of (–)-loliolide isolated from Sargassum horneri (S. horneri) against oxidative stress and inflammation, and its biological mechanism in interferon (IFN)-γ/tumor necrosis factor (TNF)-α-stimulated HaCaT keratinocytes. The results showed that (–)-loliolide improved the cell viability by reducing the production of intracellular reactive oxygen species (ROS) in IFN-γ/TNF-α-stimulated HaCaT keratinocytes. In addition, (–)-loliolide effectively decreased the expression of inflammatory cytokines (interleukin (IL)-4 IL-6, IL-13, IFN-γ and TNF-α) and chemokines (CCL11 (Eotaxin), macrophage-derived chemokine (MDC), regulated on activation, normal T cell expressed and secreted (RANTES), and thymus and activation-regulated chemokine (TARC)), by downregulating the expression of epidermal-derived initial cytokines (IL-25, IL-33 and thymic stromal lymphopoietin (TSLP)). Furthermore, (–)-loliolide suppressed the activation of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling, whereas it activated nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling. Interestingly, the cytoprotective effects of (–)-loliolide against IFN-γ/TNF-α stimulation were significantly blocked upon inhibition of HO-1. Taken together, these results suggest that (–)-loliolide effectively suppressed the oxidative stress and inflammation by activating the Nrf2/HO-1 signaling in IFN-γ/TNF-α-stimulated HaCaT keratinocytes.

Highlights

The incidence of various inflammatory diseases has increased due to many factors, such as diet, stress, and environmental factors [1]
We investigated the effects of (–)-loliolide on the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling, known as an antioxidant system in IFN-γ/tumor necrosis factor (TNF)-α in HaCaT keratinocytes
They are significantly abolabolished by the pretreatment of zinc protoporphyrin (ZnPP), a HO-1 inhibitor (Figure 5B,C). These results ished by the pretreatment of ZnPP, a HO-1 inhibitor (Figure 5B,C). These results suggest that the activation of HO-1 is required for the cytoprotective effects of (–)-loliolide in IFNγ/TNF-α-stimulated HaCaT keratinocytes

Summary

Introduction

The incidence of various inflammatory diseases has increased due to many factors, such as diet, stress, and environmental factors [1]. Antioxidants 2021, 10, 856 against irritants [2]. Recent studies have reported that epidermal initial stimulating factors (interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP)) are the first to be involved in inflammatory reactions in keratinocytes [5]. These cytokines activate other inflammatory cytokines (IL-4, IL-6, IL-13, TNF-α and IFN-γ) and chemokines (CCL11 (Eotaxin), macrophagederived chemokine (MDC), regulated on activation normal T cell expressed and secreted (RANTES), thymus and activation-regulated chemokine (TARC)), thereby leading to more severe inflammation [6]

Methods

Discussion

Conclusion