title: The antinociceptive effect and mechanism of action of SY0916.
abstract: Pain greatly affects the quality of life of people worldwide. Despite their demonstrated efficacy, currently used opioid drugs and nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently associated with several adverse events. The identification of new therapeutic targets and the development of corresponding analgesics may represent novel approaches for effectively treating pain. SY0916 is a novel compound that was designed and synthesized by the Institute of Materia Medica, Chinese Academy of Medical Sciences. As demonstrated by the hot plate test, tail-flick test and the formalin test, SY0916 exerted strong peripheral and central antinociceptive effects. Western blot, immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) results indicate that SY0916 induces its peripheral antinociceptive effect by suppressing the peripheral activity of inflammatory mediators such as prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-α) and 5-hydroxytryptamine (5-HT). Moreover, its central antinociceptive effect might be mediated by the down-regulation of PGE2 and TNF-α expression and the inhibition of p-p38 and NF-κB pathway signaling in glial cells. These findings demonstrate that SY0916 may serve as a promising analgesic candidate drug.
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Haijing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: wlq@imm.ac.cn.
authors.forename: Lianqiu
authors.initials: L
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Shanying
authors.initials: S
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: wwenj@imm.ac.cn.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Wang
mesh_terms: D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D015232:Dinoprostone / Q000097:blood / Q000378:metabolism; D005260:Female; D005557:Formaldehyde; D006358:Hot Temperature / Q000009:adverse effects; D007659:Ketones / Q000494:pharmacology* / Q000627:therapeutic use*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010146:Pain / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000097:blood / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism
chemical_list: D000700:Analgesics; D007659:Ketones; D016328:NF-kappa B; D010880:Piperidines; C550310:SY0916; D014409:Tumor Necrosis Factor-alpha; D005557:Formaldehyde; D012701:Serotonin; D020928:Mitogen-Activated Protein Kinases; D015232:Dinoprostone
keywords: Nuclear factor-kappa B; Pain; Tumor necrosis factor-alpha; p38