3-Hydroxy-5,6-epoxy-β-ionone isolated from Sargassum horneri, inhibits fine dust induced inflammation through TLR/MyD88 mediated anti-inflammatory pathway and Nrf2/HO-1 mediated antioxidant pathways

Abstract

In East-Asia region (China, Korea, and Japan) fine dust (FD) have become a major threat of air pollutions and causing negative health effects on human skin, respiratory system, and digestive system. Specifically, the extensive arid or semiarid highlands of northern China and Mongolia (Gobi Desert, Hunshdak Sandy Lands, Loess Plateau, and Taklimakan desert) are considering as the major sources of dust in Asia region. However, coal-burning power plants, rapid developments in industrialization, numerous petroleum vehicles, and large-scale mining operations have contributed to increase the FD concentration in the urban areas located in East-Asia region. Continuous exposure to air pollution such as FD can induce oxidative stress, inflammation, and poses a serious risk to human health. Alveolar macrophages, who lives in lower respiratory tract are capable to phagocyte FD particles reach the lower respiratory. However, depending on the size and particle composition, exposed macrophages may produce inflammatory responses. Recently, several studies reported that, the exposure of FD to macrophages led to inflammatory responses in macrophages including RAW 264.7 cells. According to the recent studies, the exposure of macrophages to FD triggers inflammatory responses in macrophages via altering multiple cell signaling pathways. The endotoxins presented in FD particles found to induce the toll-like receptor-4 mediated inflammation, and reactive oxygen species induce pro-inflammatory cytokine production in macrophages. The continuous/uncontrolled inflammatory activities leading to develop chronic inflammatory responses and end up with the pathogenesis of catastrophic disease conditions like cancer and immunomodulatory diseases. In addition, dust particles inside of the lungs attacked/consumed by alveolar macrophages, and then activated cells removed by lysosomes. Thus, number of healthy macrophages decrease and which might affect to the immune system that further results in less immunity in our body. Therefore, it is very important to down-regulate inflammation induced by FD particles to reduce health concerns associated with FD. Besides the respiratory system, FD also has a possibility to damage digestive system as some part of inhaled dust moved to the digestive system and directly going to the digestive tract with FD contaminated foods. Thus, effect of FD to digestive system cannot neglect and require in-depth studies to expose it effects on a digestive system like inflammation and oxidative stress. According to the statistics cancer incidents reported from colon and rectum were nearly doubled from 1999 to 2012 period, where lung cancer levels were remaining constant in that period. Other than the bad food habits FD also might responsible for this increased levels of colon and rectum cancers. Therefore, author also attempted to evaluate effect of fine dust using digestive tract epithelial cells. CMT-93 is an epithelial cell line separated from a 19 months old male mouse rectum. Recent studies carried out with CMT-93 reported the exposure of CMT-93 to LPS, triggers the inflammatory responses in CMT-93 cells. Therefore, CMT-93 cell model is a promising model to evaluate complication associated with the inflammation in digestive system. However, use of in vitro results for the development of functional materials have limited possibility as the culture cells were maintained in artificial conditions. Therefore, to validate in vitro results it is compulsory to use in vivo research models. Recently, zebrafish (Danio rerio) has been recognized as a promising in vivo model to use in research areas such as cancer, stem cell research and immunology and infectious diseases research due to its morphological and physiological similarity to the mammals, transparency, easy to handle, and less maintenance cost. Other than that, the optical transparency of zebrafish embryos allows for non-destructive and live imaging of the inflammatory responses developed in embryos. Due to these specific morphological and physiological features of zebrafish models provide great opportunities to accelerate the process of drug discovery including target identification, disease modelling, lead discovery, and toxicology. Taken together, during this study author attempted to screen seaweeds with potential anti-inflammatory compounds to develop as a functional ingredient to act against FD induced inflammatory complications. For preliminary screening author used 4 seaweeds (Ecklonia cava, Ishige okamurae, Sargassum horneri, and Porphyra yezoensis). According to the results, Sargassum horneri and Ecklonia cava had strong anti-inflammatory properties against FD-induced inflammation in macrophage cells. Moreover, our results reviled that the treatment of 3-Hydroxy-5,6-epoxy-β-ionone, the active compound isolated from S. horneri blocked the FD-induced inflammation via inhibiting NF-κB, MAPK, and NRF2/HO-1 signal pathways. The evidence in this study providing solid information's to develop functional materials from S. horneri against dust induced inflammation.