title: Pyrroloquinoline quinone (PQQ) inhibits lipopolysaccharide induced inflammation in part via downregulated NF-κB and p38/JNK activation in microglial and attenuates microglia activation in lipopolysaccharide treatment mice.
abstract: Therapeutic strategies designed to inhibit the activation of microglia may lead to significant advancement in the treatment of most neurodegenerative diseases. Pyrroloquinoline quinone (PQQ) is a naturally occurring redox cofactor that acts as an essential nutrient, antioxidant, and has been reported to exert potent immunosuppressive effects. In the present study, the anti-inflammatory effects of PQQ was investigated in LPS treated primary microglia cells. Our observations showed that pretreatment with PQQ significantly inhibited the production of NO and PGE2 and suppressed the expression of pro-inflammatory mediators such as iNOS, COX-2, TNF-a, IL-1b, IL-6, MCP-1 and MIP-1a in LPS treated primary microglia cells. The nuclear translocation of NF-κB and the phosphorylation level of p65, p38 and JNK MAP kinase pathways were also inhibited by PQQ in LPS stimulated primary microglia cells. Further a systemic LPS treatment acute inflammation murine brain model was used to study the suppressive effects of PQQ against neuroinflammation in vivo. Mice treated with PQQ demonstrated marked attenuation of neuroinflammation based on Western blotting and immunohistochemistry analysis of Iba1-against antibody in the brain tissue. Indicated that PQQ protected primary cortical neurons against microglia-mediated neurotoxicity. These results collectively suggested that PQQ might be a promising therapeutic agent for alleviating the progress of neurodegenerative diseases associated with microglia activation.
authors.affiliation: Institute of Orthopaedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Chongfei
authors.initials: C
authors.lastname: Yang
authors.affiliation: Institute of Orthopaedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Yu
authors.affiliation: Hong-Hui Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, China.
authors.forename: Lingbo
authors.initials: L
authors.lastname: Kong
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Ma
authors.affiliation: Institute of Orthopaedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Juliang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Orthopaedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Qingsheng
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Institute of Orthopaedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Jinyu
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Hong-Hui Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, China.
authors.forename: Dingjun
authors.initials: D
authors.lastname: Hao
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D004353:Drug Evaluation, Preclinical; D004789:Enzyme Activation; D005260:Female; D015870:Gene Expression; D018836:Inflammation Mediators / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D045542:PQQ Cofactor / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational; D051996:Transcription Factor RelA / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C491049:Aif1 protein, mouse; D000893:Anti-Inflammatory Agents; D002135:Calcium-Binding Proteins; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D008840:Microfilament Proteins; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D045542:PQQ Cofactor; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone