title: Anti-Inflammatory Effects of Chloranthalactone B in LPS-Stimulated RAW264.7 Cells.
abstract: Chloranthalactone B (CTB), a lindenane-type sesquiterpenoid, was obtained from the Chinese medicinal herbSarcandra glabra, which is frequently used as a remedy for inflammatory diseases. However, the anti-inflammatory mechanisms of CTB have not been fully elucidated. In this study, we investigated the molecular mechanisms underlying these effects in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. CTB strongly inhibited the production of nitric oxide and pro-inflammatory mediators such as prostaglandin E₂, tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6 in RAW264.7 cells stimulated with LPS. A reverse-transcription polymerase chain reaction assay and Western blot further confirmed that CTB inhibited the expression of inducible nitric oxide synthase, cyclooxygenase-2, TNF-α, and IL-1β at the transcriptional level, and decreased the luciferase activities of activator protein (AP)-1 reporter promoters. These data suggest that inhibition occurred at the transcriptional level. In addition, CTB blocked the activation of p38 mitogen-activated protein kinase (MAPK) but not c-Jun N-terminal kinase or extracellular signal-regulated kinase 1/2. Furthermore, CTB suppressed the phosphorylation of MKK3/6 by targeting the binding sites via formation of hydrogen bonds. Our findings clearly show that CTB inhibits the production of inflammatory mediators by inhibiting the AP-1 and p38 MAPK pathways. Therefore, CTB could potentially be used as an anti-inflammatory agent.
authors.affiliation: Department of Gerontology, Huai'an First People's Hospital, Nanjing Medical University, Huaian 223300, China. doctorlixq@sina.com.
authors.forename: Xueqin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurology, Huai'an Hospital Affiliated of Xuzhou Medical College and Huai'an Second People's Hospital, Huaian 223300, China. sj30918@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Shen
authors.affiliation: Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China. yunyao86@126.com.|Shineway Pharmaceutical Group Co., Ltd., Shijiazhuang 051430, China. yunyao86@126.com.
authors.forename: Yunyao
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Huaian 223300, China. shenting1019@163.com.|Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian 223300, China. shenting1019@163.com.
authors.forename: Ting
authors.initials: T
authors.lastname: Shen
authors.affiliation: Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Huaian 223300, China. Long_YOU66@163.com.|Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian 223300, China. Long_YOU66@163.com.
authors.forename: Long
authors.initials: L
authors.lastname: You
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China. xbsun@implad.ac.cn.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Sun
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China. xdxu@implad.ac.cn.
authors.forename: Xudong
authors.initials: X
authors.lastname: Xu
authors.affiliation: Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Huaian 223300, China. hu_weicheng@163.com.|Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian 223300, China. hu_weicheng@163.com.
authors.forename: Weicheng
authors.initials: W
authors.lastname: Hu
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China. hfwu@implad.ac.cn.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Urology, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing West Road, Huaian 223300, China. wgc1955@sina.com.
authors.forename: Gongcheng
authors.initials: G
authors.lastname: Wang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005786:Gene Expression Regulation; D007249:Inflammation / Q000517:prevention & control; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D007783:Lactones / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D048371:MAP Kinase Kinase 3 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D048669:MAP Kinase Kinase 6 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D015850:Interleukin-6; D007783:Lactones; D008070:Lipopolysaccharides; D012717:Sesquiterpenes; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; C000616592:chloranthalactone B; C577686:interleukin-6, mouse; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D048031:JNK Mitogen-Activated Protein Kinases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D048371:MAP Kinase Kinase 3; D048669:MAP Kinase Kinase 6; C482531:Map2k3 protein, mouse; C482567:Map2k6 protein, mouse; D015232:Dinoprostone
keywords: Sarcandra glabra; chloranthalactone B; inflammation; sesquiterpene