title: 15-O-Acetyl-3-O-benzoylcharaciol and helioscopinolide A, two diterpenes isolated from Euphorbia helioscopia suppress microglia activation.
abstract: Microglia activation plays an important role in the pathogenesis of various neurodegenerative diseases by producing neurotoxic factors. In the present study, we found that two diterpenes isolated from Euphorbia helioscopia, 15-O-Acetyl-3-O-benzoylcharaciol and helioscopinolide A suppressed NO and PGE2 production by inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in lipopolysaccharide (LPS)-stimulated BV2 microglia cells. The diterpenes also inhibited the production of ROS and proinflammatory cytokines including interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α, the mechanism involved the NF-κB but not Akt and mitogen-activated protein kinase (MAPK) pathway. Moreover, the two diterpenes also attenuate microglia activation-mediated neuronal death. These results suggest that 15-O-Acetyl-3-O-benzoylcharaciol and helioscopinolide A may provide potential therapeutic strategy for various neuroinflammatory diseases.
authors.affiliation: College of Pharmacy, Nankai University, Tianjin 300071, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Medicine, Nankai University, Tianjin 300071, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, School of Medicine, Nankai University, Tianjin 300071, China.
authors.forename: Jingling
authors.initials: J
authors.lastname: Zhang
authors.affiliation: College of Pharmacy, Nankai University, Tianjin 300071, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: School of Basic Medical Science, Yanbian University, Yanji 133000, China.
authors.forename: Chun-Ai
authors.initials: CA
authors.lastname: Cui
authors.affiliation: College of Pharmacy, Nankai University, Tianjin 300071, China. Electronic address: victgyq@163.com.
authors.forename: Yuanqiang
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Pharmacology, School of Medicine, Nankai University, Tianjin 300071, China. Electronic address: dqjin@nankai.edu.cn.
authors.forename: Da-Qing
authors.initials: DQ
authors.lastname: Jin
mesh_terms: D045784:Abietanes / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001565:Benzoates / Q000302:isolation & purification / Q000494:pharmacology*; D016923:Cell Death; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D028481:Euphorbia / Q000737:chemistry*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism
chemical_list: C000608596:15-O-acetyl-3-O-benzoylcharaciol; D045784:Abietanes; D000893:Anti-Inflammatory Agents; D001565:Benzoates; D016207:Cytokines; D004224:Diterpenes; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; C487257:helioscopinolide A; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2
keywords: COX-2; Cytokine; Euphorbia helioscopia; Microglia; NF-κB; iNOS