title: Ampelopsin attenuates lipopolysaccharide-induced inflammatory response through the inhibition of the NF-κB and JAK2/STAT3 signaling pathways in microglia.
abstract: Increasing evidence suggests that microglia are a major cellular contributor to neuroinflammation. The present study investigated whether Ampelopsin (Amp), a type of flavanonol derivative from Ampelopsis grossedentata, may exert an anti-inflammatory effect on lipopolysaccharide (LPS)-induced BV2 and primary microglia cells. We found that pre-treatment of microglia cells with Amp before LPS with a non-cytotoxic concentration range decreased the production of nitric oxide (NO) and prostaglandin E2 (PGE2). Amp also suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the mRNA and protein levels. In addition, LPS-induced production of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) was obviously reduced by Amp. Our mechanistic study indicated that Amp suppressed LPS-induced activation of the IκB/NF-κB inflammation pathway without affecting changes in the phosphorylation levels of mitogen-activated protein kinases (MAPKs) in BV2 cells. Further studies revealed that Amp markedly reduced the phosphorylation levels of JAK2-STAT3 and STAT3 nuclear translocation. Overall, our data suggest that Amp can suppress the LPS-induced inflammatory response of microglial cells, indicating that Amp has potential for the treatment of inflammation-mediated neurodegenerative diseases.
authors.affiliation: Department of Neurology, Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, PR China.
authors.forename: Leihua
authors.initials: L
authors.lastname: Weng
authors.affiliation: Department of Neurology, Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, PR China.
authors.forename: He
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, PR China.
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurology, Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhan
authors.affiliation: Department of Neurology, Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, PR China.
authors.forename: Fan
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Neurology, Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, PR China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Neurology, Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, PR China; Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, Nanjing, Jiangsu 210008, PR China. Electronic address: xuyun20042001@aliyun.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Neurology, Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, PR China; Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, Nanjing, Jiangsu 210008, PR China. Electronic address: xiangcao1988@163.com.
authors.forename: Xiang
authors.initials: X
authors.lastname: Cao
mesh_terms: D032421:Ampelopsis / Q000276:immunology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D053614:Janus Kinase 2 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects* / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism*; D020078:Neurogenic Inflammation / Q000188:drug therapy* / Q000276:immunology; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005419:Flavonoids; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C106407:ampelopsin; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2; D015232:Dinoprostone
keywords: Ampelopsin·microglia·neuroinflammation·lipopolysaccharide·NF-κB·JAK2/STAT3