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
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{"title"=>"Pyrroloquinoline quinone (PQQ) inhibits lipopolysaccharide induced inflammation in part via downregulated NF-kB and p38/JNK activation in microglial and attenuates microglia activation in lipopolysaccharide treatment mice", "type"=>"journal", "authors"=>[{"first_name"=>"Chongfei", "last_name"=>"Yang", "scopus_author_id"=>"7407739739"}, {"first_name"=>"Lifeng", "last_name"=>"Yu", "scopus_author_id"=>"55652343800"}, {"first_name"=>"Lingbo", "last_name"=>"Kong", "scopus_author_id"=>"55651811000"}, {"first_name"=>"Rui", "last_name"=>"Ma", "scopus_author_id"=>"57189626595"}, {"first_name"=>"Juliang", "last_name"=>"Zhang", "scopus_author_id"=>"7601343242"}, {"first_name"=>"Qingsheng", "last_name"=>"Zhu", "scopus_author_id"=>"35083026700"}, {"first_name"=>"Jinyu", "last_name"=>"Zhu", "scopus_author_id"=>"7405690138"}, {"first_name"=>"Dingjun", "last_name"=>"Hao", "scopus_author_id"=>"55578851400"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"25314304", "doi"=>"10.1371/journal.pone.0109502", "pui"=>"600170362", "issn"=>"19326203", "sgr"=>"84908141370", "scopus"=>"2-s2.0-84908141370"}, "id"=>"d6ac07ad-28f6-35c1-9ff2-9736d46b473a", "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-kappaB 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.", "link"=>"http://www.mendeley.com/research/pyrroloquinoline-quinone-pqq-inhibits-lipopolysaccharide-induced-inflammation-part-via-downregulated", "reader_count"=>17, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>1, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>1, "Other"=>2, "Student > Master"=>1, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>1, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>1, "Other"=>2, "Student > Master"=>1, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>2, "Medicine and Dentistry"=>2, "Agricultural and Biological Sciences"=>3, "Neuroscience"=>4, "Design"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Chemistry"=>1, "Engineering"=>1}, "reader_count_by_subdiscipline"=>{"Design"=>{"Design"=>1}, "Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Neuroscience"=>{"Neuroscience"=>4}, "Chemistry"=>{"Chemistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1717230"], "description"=>"<p>Representative Western blots illustrate differences in the bands of Iba-1 (A). LPS up-regulates Iba-1 expression in brain tissue, while PQQ treatment attenuates up-regulation of Iba-1 expression at doses of 3 and 10 mg/kg administration (B). The results shown are mean ± S.E.M. (<i>n</i> = 6 in each group) of three independent experiments. <i>*p<0.05 vs. control group, #p<0.05 vs. only LPS group.</i></p>", "links"=>[], "tags"=>["mip", "lps", "Attenuates Microglia Activation", "microglia cells", "pqq", "Neurodegenerative diseases", "inflammation murine brain model", "cox", "nf", "Lipopolysaccharide Treatment Mice Therapeutic strategies", "Inhibits Lipopolysaccharide Induced Inflammation", "pge", "il", "JNK MAP kinase pathways", "mcp"], "article_id"=>1204318, "categories"=>["Biological Sciences"], "users"=>["Chongfei Yang", "Lifeng Yu", "Lingbo Kong", "Rui Ma", "Juliang Zhang", "Qingsheng Zhu", "Jinyu Zhu", "Dingjun Hao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0109502.g006", "stats"=>{"downloads"=>1, "page_views"=>30, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_PQQ_on_Iba_1_Expression_in_the_Brain_/1204318", "title"=>"Effect of PQQ on Iba-1 Expression in the Brain.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-14 03:44:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/1717174"], "description"=>"<p>Structure of pyrroloquinoline quinone (PQQ).</p>", "links"=>[], "tags"=>["mip", "lps", "Attenuates Microglia Activation", "microglia cells", "pqq", "Neurodegenerative diseases", "inflammation murine brain model", "cox", "nf", "Lipopolysaccharide Treatment Mice Therapeutic strategies", "Inhibits Lipopolysaccharide Induced Inflammation", "pge", "il", "JNK MAP kinase pathways", "mcp"], "article_id"=>1204268, "categories"=>["Biological Sciences"], "users"=>["Chongfei Yang", "Lifeng Yu", "Lingbo Kong", "Rui Ma", "Juliang Zhang", "Qingsheng Zhu", "Jinyu Zhu", "Dingjun Hao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0109502.g001", "stats"=>{"downloads"=>0, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Structure_of_pyrroloquinoline_quinone_PQQ_/1204268", "title"=>"Structure of pyrroloquinoline quinone (PQQ).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-14 03:44:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/1717280"], "description"=>"<p>Representative photographs show Iba-1 immuno-stained microglia of the mouse brain (A). LPS group shows mostly an activated-form of microglia which display an increased size, irregular shape, thickened and shortened processes and intensified Iba-1 immunostaining density, in the dentate gyrus of hippocampus (DG) and cerebral cortex (Cortex) compared to the normal group. Moreover, both PQQ treated groups show a decrease of morphological activation of microglia in all brain regions with respect to LPS group. Representative DG (a–d) and Cortex (e–h) immunostained slices are presented at ×40. High power images of Iba-1-expressed microglia in the boxed regions in (f), (g) and (h) are also shown at×200 (i–l). Arrow indicates the Iba-1-expressed microglia. The number of microglia was counted and normalized in the corresponding same area (B). LPS increases the number of Iba-1-expressed microglia in the brain. PQQ treatment significantly reduces the number of Iba-1-expressed microglia both in the cerebral cortex and DG. The results shown are mean ± S.E.M. (<i>n</i> = 6 in each group) of three independent experiments. <i>*p<0.05 vs. control group, #p<0.05 vs. only LPS group.</i></p>", "links"=>[], "tags"=>["mip", "lps", "Attenuates Microglia Activation", "microglia cells", "pqq", "Neurodegenerative diseases", "inflammation murine brain model", "cox", "nf", "Lipopolysaccharide Treatment Mice Therapeutic strategies", "Inhibits Lipopolysaccharide Induced Inflammation", "pge", "il", "JNK MAP kinase pathways", "mcp"], "article_id"=>1204367, "categories"=>["Biological Sciences"], "users"=>["Chongfei Yang", "Lifeng Yu", "Lingbo Kong", "Rui Ma", "Juliang Zhang", "Qingsheng Zhu", "Jinyu Zhu", "Dingjun Hao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0109502.g007", "stats"=>{"downloads"=>2, "page_views"=>27, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_PQQ_on_Microglia_Activation_in_the_Brain_/1204367", "title"=>"Effect of PQQ on Microglia Activation in the Brain.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-14 03:44:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/1717209"], "description"=>"<p>(A) Representative images of NF-κB p65 in microglial cells of each group. Cells were pretreated with or without PQQ for 1 h followed by 100 ng/ml LPS treatment for 2 h. Microglial cells were incubated with NF-κB p65 antibody and immunofluorescence microscopy was used to visualize the localization of NF-κB p65 (Green; a-c), boxed regions in (a-c) are also shown at×200 (j-m). Nuclei were visualized using DAPI counterstaining (Blue; d-f). (B) Cells were treated with 100 ng/m LPS for indicated time. p65 protein level was measured by western blot analysis. Non-phosphorylated p65 was used as loading control, and the expression of p-p65 was normalized to control and quantified by densitometric analysis. The results shown are mean ± S.E.M. of three independent experiments. <i>*p<0.05 vs. control group, #p<0.05 vs. only LPS group.</i></p>", "links"=>[], "tags"=>["mip", "lps", "Attenuates Microglia Activation", "microglia cells", "pqq", "Neurodegenerative diseases", "inflammation murine brain model", "cox", "nf", "Lipopolysaccharide Treatment Mice Therapeutic strategies", "Inhibits Lipopolysaccharide Induced Inflammation", "pge", "il", "JNK MAP kinase pathways", "mcp"], "article_id"=>1204299, "categories"=>["Biological Sciences"], "users"=>["Chongfei Yang", "Lifeng Yu", "Lingbo Kong", "Rui Ma", "Juliang Zhang", "Qingsheng Zhu", "Jinyu Zhu", "Dingjun Hao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0109502.g004", "stats"=>{"downloads"=>2, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_PQQ_on_LPS_induced_p65_and_NF_954_B_activity_in_microglial_cells_/1204299", "title"=>"Effects of PQQ on LPS-induced p65 and NF-κB activity in microglial cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-14 03:44:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/1717223"], "description"=>"<p>(A) Microglial cells were treated with or without PQQ 1 h prior to 4 h co-treatment with LPS. The protein expression of p-p38 and p-JNK was determined by western blot analysis. Non-phosphorylated form of each targeted protein was used as loading control. (B) Bar graph represents the average levels of p-p38 and p-JNK compared to the control. The results shown are mean ± S.E.M. of three independent experiments. <i>*p<0.05 vs. control group, #p<0.05 vs. only LPS group.</i></p>", "links"=>[], "tags"=>["mip", "lps", "Attenuates Microglia Activation", "microglia cells", "pqq", "Neurodegenerative diseases", "inflammation murine brain model", "cox", "nf", "Lipopolysaccharide Treatment Mice Therapeutic strategies", "Inhibits Lipopolysaccharide Induced Inflammation", "pge", "il", "JNK MAP kinase pathways", "mcp"], "article_id"=>1204311, "categories"=>["Biological Sciences"], "users"=>["Chongfei Yang", "Lifeng Yu", "Lingbo Kong", "Rui Ma", "Juliang Zhang", "Qingsheng Zhu", "Jinyu Zhu", "Dingjun Hao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0109502.g005", "stats"=>{"downloads"=>0, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_PQQ_on_LPS_induced_MAP_kinases_activity_in_microglial_cells_/1204311", "title"=>"Effects of PQQ on LPS-induced MAP kinases activity in microglial cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-14 03:44:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/1717181"], "description"=>"<p>Primary microglia were pretreated with or without PQQ for 1 h followed by LPS (100 ng/ml) treatment for indicated durations. Culture supernatants were collected 24 h later, the released NO in primary microglia (A) was determined by the Griess assay, total mRNA was harvested 6 h later, and the mRNA level of iNOS (B) and COX-2 (D) was measured by real-time PCR. (C) Concentrations of PGE2 in the culture supernatants of primary microglia were determined by ELISA. (E) 24 h later, the protein level of iNOS and COX-2 were detected by western blot analysis in primary microglia cells. The results presented as mean ± S.E.M. of at least three independent experiments, <i>*p<0.05 vs. control group, #p<0.05 vs. only LPS group.</i></p>", "links"=>[], "tags"=>["mip", "lps", "Attenuates Microglia Activation", "microglia cells", "pqq", "Neurodegenerative diseases", "inflammation murine brain model", "cox", "nf", "Lipopolysaccharide Treatment Mice Therapeutic strategies", "Inhibits Lipopolysaccharide Induced Inflammation", "pge", "il", "JNK MAP kinase pathways", "mcp"], "article_id"=>1204275, "categories"=>["Biological Sciences"], "users"=>["Chongfei Yang", "Lifeng Yu", "Lingbo Kong", "Rui Ma", "Juliang Zhang", "Qingsheng Zhu", "Jinyu Zhu", "Dingjun Hao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0109502.g002", "stats"=>{"downloads"=>2, "page_views"=>102, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_PQQ_on_LPS_induced_NO_PGE2_production_and_iNOS_COX_2_expression_in_microglia_cells_/1204275", "title"=>"Effects of PQQ on LPS-induced NO, PGE2 production and iNOS, COX-2 expression in microglia cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-14 03:44:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/1717197"], "description"=>"<p>Cells were treated with the indicated concentrations of PQQ 1 h prior to 6 h co-treatment of LPS (100 ng/ml). Primary microglia were harvested and total RNA was prepared. The mRNA expression of pro-inflammatory mediators: TNF-a, IL-1β, IL-6, COX-2, MCP-1 and MIP-1α was measured by real-time PCR. GAPDH was used as an internal control. The results shown are mean ± S.E.M. of three independent experiments. <i>*p<0.05 vs. control group, #p<0.05 vs. only LPS group.</i></p>", "links"=>[], "tags"=>["mip", "lps", "Attenuates Microglia Activation", "microglia cells", "pqq", "Neurodegenerative diseases", "inflammation murine brain model", "cox", "nf", "Lipopolysaccharide Treatment Mice Therapeutic strategies", "Inhibits Lipopolysaccharide Induced Inflammation", "pge", "il", "JNK MAP kinase pathways", "mcp"], "article_id"=>1204287, "categories"=>["Biological Sciences"], "users"=>["Chongfei Yang", "Lifeng Yu", "Lingbo Kong", "Rui Ma", "Juliang Zhang", "Qingsheng Zhu", "Jinyu Zhu", "Dingjun Hao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0109502.g003", "stats"=>{"downloads"=>1, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_PQQ_on_LPS_stimulated_expression_of_pro_inflammatory_mediators_in_microglial_cells_/1204287", "title"=>"Effects of PQQ on LPS-stimulated expression of pro-inflammatory mediators in microglial cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-14 03:44:38"}

PMC Usage Stats | Further Information

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Relative Metric

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