title: Pinocembrin protects human brain microvascular endothelial cells against fibrillar amyloid-β(1-40) injury by suppressing the MAPK/NF-κB inflammatory pathways.
abstract: Cerebrovascular accumulation of amyloid-β (Aβ) peptides in Alzheimer's disease (AD) may contribute to disease progression through Aβ-induced microvascular endothelial pathogenesis. Pinocembrin has been shown to have therapeutic effects in AD models. These effects correlate with preservation of microvascular function, but the effect on endothelial cells under Aβ-damaged conditions is unclear. The present study focuses on the in vitro protective effect of pinocembrin on fibrillar Aβ(1-40) (fAβ(1-40)) injured human brain microvascular endothelial cells (hBMECs) and explores potential mechanisms. The results demonstrate that fAβ(1-40)-induced cytotoxicity in hBMECs can be rescued by pinocembrin treatment. Pinocembrin increases cell viability, reduces the release of LDH, and relieves nuclear condensation. The mechanisms of this reversal from Aβ may be associated with the inhibition of inflammatory response, involving inhibition of MAPK activation, downregulation of phosphor-IKK level, relief of IκBα degradation, blockage of NF-κB p65 nuclear translocation, and reduction of the release of proinflammatory cytokines. Pinocembrin does not show obvious effects on regulating the redox imbalance after exposure to fAβ(1-40). Together, the suppression of MAPK and the NF-κB signaling pathways play a significant role in the anti-inflammation of pinocembrin in hBMECs subjected to fAβ(1-40). This may serve as a therapeutic agent for BMEC protection in Alzheimer's-related deficits.
authors.affiliation: Beijing Key Laboratory of Drug Target and Screening Research, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Rui
authors.identifier: 0000-0003-2233-125X
authors.initials: R
authors.lastname: Liu
authors.affiliation: Beijing Key Laboratory of Drug Target and Screening Research, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Jin-ze
authors.initials: JZ
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory of Drug Target and Screening Research, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Jun-ke
authors.initials: JK
authors.lastname: Song
authors.affiliation: Beijing Key Laboratory of Drug Target and Screening Research, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China ; Pharmacy Department, the Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, China.
authors.forename: Jia-lin
authors.initials: JL
authors.lastname: Sun
authors.affiliation: Beijing Key Laboratory of Drug Target and Screening Research, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Yong-jie
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory of Drug Target and Screening Research, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Si-bai
authors.initials: SB
authors.lastname: Zhou
authors.affiliation: Beijing Key Laboratory of Drug Target and Screening Research, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Tian-tai
authors.identifier: 0000-0001-5804-5293
authors.initials: TT
authors.lastname: Zhang
authors.affiliation: Beijing Key Laboratory of Drug Target and Screening Research, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Guan-hua
authors.initials: GH
authors.lastname: Du
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D001921:Brain / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D055806:Microvessels / Q000187:drug effects / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D016207:Cytokines; D044950:Flavanones; D018836:Inflammation Mediators; D016328:NF-kappa B; D018696:Neuroprotective Agents; C016063:pinocembrin; D020928:Mitogen-Activated Protein Kinases