Aucubin suppresses lipopolysaccharide-induced pro-inflammatory responses by blocking the NF-κB translocation signaling pathways in activated microglial cells |
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| Institution: | 1. College of Pharmacy, Kyungsung University, Busan 48434, Republic of Korea;2. Department of Biological Sciences, University of University of Maryland, Baltimore County, Baltimore, MD 21250, USA;3. Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA;4. College of Korean Medicine, Gachon University, Seongnam-si, Gyeonggi-do 13120, Republic of Korea;1. State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences; Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming 650201, People''s Republic of China;2. School of Life Sciences, Yunnan University, Kunming 650500, People''s Republic of China;1. Hubei Key Laboratory of Natural Products Research and Development, Key Laboratory of Functional Yeast (China National Light Industry), College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang, PR China;2. Hubei Hongyu New Packing Materials Co., Ltd., Yichang, PR China;1. Department of Food Science, Tunghai University, No. 1727, Sec. 4, Taiwan Boulevard, Xitun District, Taichung, 40704, Taiwan;2. Department of Radiation Oncology, Taichung Veterans General Hospital, No. 1650, Sec. 4, Taiwan Boulevard, Xitun District, Taichung, 40705, Taiwan;1. Faculty of Engineering, University of Miyazaki, Gakuen-Kibanadai, Miyazaki, 889-2192, Japan;2. Center for Collaborative Research and Community Cooperation, University of Miyazaki, Gakuen-Kibanadai, Miyazaki, 889-2192, Japan;3. Sunao Pharma Inc., Miyazaki, 880-0866, Japan |
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| Abstract: | Aucubin is an iridoid glycoside with demonstrable hepatoprotective and anti-osteoporotic effects. Herein, using microglial cells and lipopolysaccharide (LPS) to induce inflammatory responses, we studied the signaling pathways involved in the anti-inflammatory action of aucubin and their influence on the expression of several genes known to be involved in inflammation. Aucubin inhibited LPS-stimulated pro-inflammatory responses by suppressing the production of nitric oxide and prostaglandin E2. Furthermore, aucubin inhibited inducible nitric oxide synthase and cyclooxygenase-2 at both the protein and mRNA levels. In addition, aucubin inhibited pro-inflammatory cytokine production in LPS-stimulated BV-2 microglial cells. Subsequent mechanistic studies revealed that aucubin inhibited the LPS-induced activation of nuclear factor-kappa B (NF-κB) translocation and phosphorylation of phosphatidylinositol 3-kinases (PI3K)/Akt as well as of mitogen-activated protein kinases (MAPKs), which are upstream molecules responsible for controlling inflammatory reactions. These results suggest that aucubin may exert anti-neuroinflammatory responses by suppressing the LPS-induced expression of pro-inflammatory mediators by blocking the activation of NF-κB, PI3K/Akt, and MAPK signaling pathways in microglial cells. |
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| Keywords: | Aucubin Lipopolysaccharide Pro-inflammatory responses Nuclear factor-kappa B Microglial cells |
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