title: Ginkgolide A Ameliorates LPS-Induced Inflammatory Responses In Vitro and In Vivo.
abstract: Ginkgolide A (GA) is a natural compound isolated fromGinkgo bilobaand has been used to treat cardiovascular diseases and diabetic vascular complications. However, only a few studies have been conducted on the anti-inflammatory effects of GA. In particular, no related reports have been published in a common inflammation model of lipopolysaccharide (LPS)-stimulated macrophages, and the anti-inflammatory mechanisms of GA have not been fully elucidated. In the present study, we extensively investigated the anti-inflammatory potential of GA in vitro and in vivo. We showed that GA could suppress the expression of pro-inflammatory mediators (cyclooxygenase-2 (COX-2) and nitric oxide (NO) and pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β) in LPS-treated mouse peritoneal macrophages, mouse macrophage RAW264.7 cells, and differentiated human monocytes (dTHP-1) in vitro. These effects were partially carried out via downregulating Nuclear factor kappa-B (NF-κB), Mitogen-activated protein kinases (MAPKs) (p38 mitogen-activated protein kinase and extracellular signal-regulated kinase (ERK), but not c-Jun N-terminal kinase (JNK), and activating the AMP-activated protein kinase (AMPK) signaling pathway also seems to be important. Consistently, GA was also shown to inhibit the LPS-stimulated release of TNF-α and IL-6 in mice. Taken together, these findings suggest that GA can serve as an effective inflammatory inhibitor in vitro and in vivo.
authors.affiliation: Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China. liy848@nenu.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China. wuyn712@nenu.edu.cn.
authors.forename: Yannan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China. yaoxl613@nenu.edu.cn.
authors.forename: Xinlei
authors.initials: X
authors.lastname: Yao
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China. haof991@nenu.edu.cn.
authors.forename: Fang
authors.initials: F
authors.lastname: Hao
authors.affiliation: Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China. yucl885@nenu.edu.cn.
authors.forename: Chunlei
authors.initials: C
authors.lastname: Yu
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China. baoyl800@nenu.edu.cn.
authors.forename: Yongli
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China. wuy705@nenu.edu.cn.
authors.forename: Yin
authors.initials: Y
authors.lastname: Wu
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China. songzb484@nenu.edu.cn.
authors.forename: Zhenbo
authors.initials: Z
authors.lastname: Song
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China. suny040@nenu.edu.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China. zhenglh015@nenu.edu.cn.
authors.forename: Lihua
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China. wanggn258@nenu.edu.cn.
authors.forename: Guannan
authors.initials: G
authors.lastname: Wang
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China. huangyx356@nenu.edu.cn.
authors.forename: Yanxin
authors.initials: Y
authors.lastname: Huang
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China. sunlg388@nenu.edu.cn.
authors.forename: Luguo
authors.initials: L
authors.lastname: Sun
authors.affiliation: Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China. liyx486@nenu.edu.cn.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D046934:Ginkgolides / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D007783:Lactones / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016207:Cytokines; D046934:Ginkgolides; D018836:Inflammation Mediators; D007783:Lactones; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009569:Nitric Oxide; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases; C477042:ginkgolide A
keywords: AMPK; Ginkgolide A; MAPKs; NF-κB; inflammation