title: Gambogenic acid inhibits LPS-simulated inflammatory response by suppressing NF-κB and MAPK in macrophages.
abstract: Inflammation is a response of body tissues to injury and infection. Compounds that can inhibit inflammation have been shown to have potential therapeutic clinical application. Gambogenic acid (GEA) has potent antitumor and anti-inflammatory activities. Herein, the molecular mechanisms of GEA's anti-inflammatory effect were investigated in lipopolysaccharide (LPS)-stimulated macrophage cells. The results showed that pretreatment with GEA could markedly inhibit interleukin (IL)-1α, IL-1β, tumor necrosis factor-α, IFN-β, IL-12b, and IL-23a production in a dose-dependent manner in LPS-induced model. Furthermore, this drug significantly reduced the release of nitric oxide (NO), and impaired the protein level of inducible NO synthase and the cyclooxygenase 2. The finding also showed that the effect of GEA may be related to the suppression of the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathway. These results indicate that GEA could suppress LPS-simulated inflammatory response partially by attenuating NO synthesis and NF-κB and MAPK activation, suggesting that it may become a potent therapeutic agent for the treatment of inflammatory diseases.
authors.affiliation: Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, China Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Xianjun
authors.initials: X
authors.lastname: Yu
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Haiwei
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Cunxian
authors.initials: C
authors.lastname: Fan
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Xixi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China Department of Anesthesiology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Xie
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Chengxian
authors.initials: C
authors.lastname: Xu
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yongbo
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Wu
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China simonhan@hkbu.edu.hk hbzhang@sibs.ac.cn.
authors.forename: Quanbin
authors.initials: Q
authors.lastname: Han
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China simonhan@hkbu.edu.hk hbzhang@sibs.ac.cn.
authors.forename: Haibing
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D014966:Xanthenes / Q000493:pharmacokinetics*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014966:Xanthenes; D009569:Nitric Oxide; C045863:neo-gambogic acid; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2
keywords: MAPK pathway; NF-κB pathway; NO; gambogenic acid; inflammation