title: Deoxysappanone B, a homoisoflavone from the Chinese medicinal plant Caesalpinia sappan L., protects neurons from microglia-mediated inflammatory injuries via inhibition of IκB kinase (IKK)-NF-κB and p38/ERK MAPK pathways.
abstract: Caesalpinia sappan L. (Lignum Sappan) is a Chinese medicinal plant for treating ischemic cerebral apoplexy. Deoxysappanone B (DSB), a homoisoflavone compound isolated from C. sappan L. (Lignum Sappan), was studied for anti-neuroinflammatory and neuroprotective properties using lipopolysaccharide (LPS)-induced BV-2 microglia neuroinflammation model and LPS-induced microglia-neuron co-culture system. Our findings showed that DSB effectively inhibited BV-2 microglia-mediated neuroinflammatory mediators׳ release including NO, PGE₂, TNF-α, IL-6 and reactive oxygen species. Moreover, DSB markedly protected neurons against inflammatory microglia-mediated neurotoxicity in a microglia-neuron co-culture system. Mechanism study revealed that DSB blocked two major neuroinflammation-related signaling pathways including IKK-IκB-nuclear factor kappaB (NF-κB) and p38/ERK mitogen-activated protein kinase (MAPK) cascades, further leading to the inhibition of neuroinflammatory mediators׳ production. The present study provides evidence that the anti-neuroinflammatory and neuroprotective effect of DSB are due to the suppression of neuroinflammatory mediators׳ production as well as inflammation-induced neurotoxicity through regulation of multi-targets. Therefore, DSB may serve as a neuroprotective agent for the treatment of neuroinflammatory disorders and inflammation-related neuronal injury.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Ke-Wu
authors.initials: KW
authors.lastname: Zeng
authors.affiliation: Research Studio of Integration of Traditional and Western Medicine, First Hospital, Peking University, Beijing 100034, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Research Studio of Integration of Traditional and Western Medicine, First Hospital, Peking University, Beijing 100034, China.
authors.forename: Fang-Jiao
authors.initials: FJ
authors.lastname: Song
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Li-Xi
authors.initials: LX
authors.lastname: Liao
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Ming-Bo
authors.initials: MB
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address: pengfeitu@vip.163.com.
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Tu
mesh_terms: D000818:Animals; D029911:Caesalpinia / Q000737:chemistry*; D002460:Cell Line; D015232:Dinoprostone / Q000096:biosynthesis; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015850:Interleukin-6 / Q000096:biosynthesis; D007529:Isoflavones / Q000494:pharmacology* / Q000627:therapeutic use; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009569:Nitric Oxide / Q000096:biosynthesis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D059748:Proteolysis / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D015850:Interleukin-6; D007529:Isoflavones; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018696:Neuroprotective Agents; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C000601539:deoxysappanone B; D009569:Nitric Oxide; D051550:I-kappa B Kinase; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone
keywords: Deoxysappanone B; Deoxysappanone B (PubChem CID: 57396358); MAPK; Microglia; NF-κB; Neuroinflammation