antioxidants Article (-)-Loliolide Isolated from Sargassum horneri Protects against Fine Dust-Induced Oxidative Stress in Human Keratinocytes Mawalle Kankanamge Hasitha Madhawa Dias 1 , Dissanayaka Mudiyanselage Dinesh Madusanka 1 , Eui Jeong Han 1 , Min Ju Kim 1 , You-Jin Jeon 2,3 , Hyun-Soo Kim 2,4 , Ilekuttige Priyan Shanura Fernando 5, * and Ginnae Ahn 1,5, * 1 Department of Food Technology and Nutrition, Chonnam National University, Yeosu 59626, Korea; 198807@jnu.ac.kr (M.K.H.M.D.); 198793@jnu.ac.kr (D.M.D.M.); iosu5772@naver.com (E.J.H.); alswn1281@nate.com (M.J.K.) 2 Department of Marine Life Science, School of Marine Biomedical Sciences, Jeju National University, Jeju 63243, Korea; youjinj@jejunu.ac.kr (Y.-J.J.); gustn783@mabik.re.kr (H.-S.K.) 3 Marine Science Institute, Jeju National University, Jeju Self-Governing Province 63333, Korea 4 National Marine Biodiversity Institute of Korea, 75, Jangsan-ro 101-gil, Janghang-eup, Seocheon 33662, Korea 5 Department of Marine Bio-Food Sciences, Chonnam National University, Yeosu 59626, Korea * Correspondence: shanura@chonnam.ac.kr (I.P.S.F.); gnahn@chonnam.ac.kr (G.A.); Tel.: +82-61-659-7213 (I.P.S.F. & G.A.) Received: 11 April 2020; Accepted: 31 May 2020; Published: 2 June 2020   Abstract: The emergence of fine dust (FD) among air pollutants has taken a toll during the past few decades, and it has provided both controversy and a platform for open conversation amongst world powers for finding sustainable solutions and effective treatments for health issues. The present study emphasizes the protective effects of (–)-loliolide (HTT) isolated from Sargassum horneri against FD-induced oxidative stress in human HaCaT keratinocytes. The purification of (–)-loliolide was carried out by centrifugal partition chromatography. HTT did not show any cytotoxicity, and it further illustrated the potential to increase cell viability by reducing the reactive oxygen species (ROS) production in FD-stimulated keratinocytes. Furthermore, HTT suppressed FD-stimulated DNA damage and the formation of apoptotic bodies, and it reduced the population of cells in the sub-G 1 apoptosis phase. FD-induced apoptosis was advancing through the mitochondria-mediated apoptosis pathway. The cytoprotective effects of the HTT against FD-stimulated oxidative damage is mediated through squaring the nuclear factor E2-related factor 2 (Nrf2)-mediated heme oxygenase-1 (HO-1) pathway, dose-dependently increasing HO-1 and NAD(P)H dehydrogenase (quinone) 1 (NQO1) levels in the cytosol while concomitantly improving the nuclear translocation of Nrf2. Future studies could implement the protective functionality of HTT in producing pharmaceuticals that utilize natural products and benefit the diseased. Keywords: Sargassum horneri; (–)-loliolide; fine dust; oxidative stress; HaCaT; apoptosis 1. Introduction Recently, air pollution has become one of the most debated environmental issues throughout the globe. A real-time air quality index has been created to alert the public regarding levels of various air quality parameters, namely temperature, humidity, pressure, and pollutants such as nitric oxide (NO 2(g) ), sulfur dioxide (SO 2(g) ), and carbon monoxide (CO (g) ) with immediate updates. This system is operational in many cities around the globe. Fine dust (FD) is one of the principal Antioxidants 2020, 9, 474; doi:10.3390/antiox9060474 www.mdpi.com/journal/antioxidants