Eupatilin Inhibits Reactive Oxygen Species Generation via Akt/NF-κB/MAPK Signaling Pathways in Particulate Matter-Exposed Human Bronchial Epithelial Cells

Abstract

Background: Eupatilin is an active flavon extracted from the Artemisia species and has properties such as antioxidant, anti-inflammatory, and anti-cancer. We examined the effect of eupatilin using fine particulate matter (FPM) and human bronchial epithelial cell line (BEAS-2B) to confirm the potential of eupatilin as a therapeutic agent for respiratory diseases caused by FPM. Methods: Reactive oxygen species (ROS) levels were checked by flow cytometry to identify if FPM and eupatilin affect ROS production. Western blotting was performed to identify the mechanism of action of eupatilin in FPM-exposed BEAS-2B cells. Results: When cells were exposed to FPM above 12.5 μg/mL concentration for 24 h, ROS production increased significantly compared to the control. When eupatilin was added to cells exposed to FPM, the ROS level decreased proportionally with the eupatilin dose. The phosphorylation of Akt, NF-κB p65, and p38 MAPK induced by FPM was significantly reduced by eupatilin, respectively. Conclusion: FPM cause respiratory disease by producing ROS in bronchial epithelial cells. Eupatilin has been shown to inhibit ROS production through altering signaling pathways. The ROS inhibiting property of eupatilin can be exploited in FPM induced respiratory disorders.

Pretreatment with Eupatilin Attenuates Inflammation and Coagulation in Sepsis by Suppressing JAK2/STAT3 Signaling Pathway

“…In addition, Eupatilin may also play a role in other pathways, such as PI3K/AKT, NF-κB, MAPK and Nrf2 pathways. 24,61 Thus, whether these pathways also play a role in regulating inflammation and coagulation in sepsis needs further investigation. According to one study, Eupatilin can lower the expression of inflammatory mediators by inhibiting the NF-κB signaling pathway in endotoxin-stimulated macrophages.…”

Ameliorative Effect of Citrus junos Tanaka Waste (By-Product) Water Extract on Particulate Matter 10-Induced Lung Damage

“…ROS are generated by various endotoxins (e.g., PM10 and LPS) to activate downstream signaling pathways in order to regulate the inflammatory response. Several studies have demonstrated that PM can trigger several signaling pathways to regulate PM10-induced inflammatory responses, including the AKT, ERK, JNK, and NF-κB signaling pathways [ 14 , 41 ]. The PI3K/AKT signaling pathway is known to play an important role in cell inflammation, apoptosis, angiogenesis, and metastasis.…”

“…PM10 (PM with an aerodynamic diameter of under 10 μm) can easily be inhaled and deposited throughout the airways, which harms the human respiratory and circulatory systems [ 12 , 13 ]. As it is mainly absorbed through respiration, many studies related to pulmonary inflammation have been conducted, while reactive oxygen species (ROS)-mediated redox responsive signaling pathways, including phosphoinositide 3-kinase (P13K)/AKT, mitogen-activated protein kinase (MAPK), and nuclear κappa B (NF-κB), have been identified as major mechanisms of action explaining its toxicity [ 14 , 15 , 16 ]. In addition, PM10-induced pulmonary oxidative stress is associated with the release of various cytokines, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β), which can promote lung damage [ 17 , 18 , 19 ].…”