Gentiolactone, a Secoiridoid Dilactone from Gentiana triflora, Inhibits TNF-α, iNOS and Cox-2 mRNA Expression and Blocks NF-κB Promoter Activity in Murine Macrophages
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{"title"=>"Gentiolactone, a secoiridoid dilactone from Gentiana triflora, inhibits TNF-α, iNOS and Cox-2 mRNA expression and blocks NF-κB promoter activity in murine macrophages", "type"=>"journal", "authors"=>[{"first_name"=>"Hidetoshi", "last_name"=>"Yamada", "scopus_author_id"=>"42462940800"}, {"first_name"=>"Sayaka", "last_name"=>"Kikuchi", "scopus_author_id"=>"26029938000"}, {"first_name"=>"Tomoki", "last_name"=>"Inui", "scopus_author_id"=>"56430510200"}, {"first_name"=>"Hideyuki", "last_name"=>"Takahashi", "scopus_author_id"=>"56843619500"}, {"first_name"=>"Ken Ichi", "last_name"=>"Kimura", "scopus_author_id"=>"56605715500"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"600596154", "doi"=>"10.1371/journal.pone.0113834", "issn"=>"19326203", "pmid"=>"25423092", "sgr"=>"84912569813", "scopus"=>"2-s2.0-84912569813"}, "id"=>"21d487cb-303b-3c2e-8cde-8d510d318938", "abstract"=>"BACKGROUND: Gentian roots have been used as a herbal medicine because of their anti-inflammatory activities. However, the molecular mechanisms of these anti-inflammatory effects remain to be completely explained.\\n\\nMETHODS AND FINDINGS: Here, we investigated anti-inflammatory effects of gentian roots and showed that root extracts from Gentiana triflora inhibited lipopolysaccharide (LPS)-induced expression of TNF-α in RAW264.7 cells. The extracts also contained swertiamarin and gentiopicroside, which are the major active compounds of gentian roots; however, neither compound had any effect on LPS-induced TNF-α production in our test system. We isolated gentiolactone as an inhibitor of TNF-α production from the extracts. Gentiolactone also inhibited LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (Cox-2) expression at the mRNA level. Moreover, gentiolactone suppressed NF-κB transcriptional activity without inhibition of IκB degradation or NF-κB nuclear transport.\\n\\nCONCLUSIONS: Our results indicate that inhibition of TNF-α, iNOS and Cox-2 expression by gentiolactone is one of the mechanisms of the anti-inflammatory properties of gentian roots.", "link"=>"http://www.mendeley.com/research/gentiolactone-secoiridoid-dilactone-gentiana-triflora-inhibits-tnf%CE%B1-inos-cox2-mrna-expression-blocks", "reader_count"=>5, "reader_count_by_academic_status"=>{"Student > Doctoral Student"=>1, "Researcher"=>1, "Student > Master"=>1, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Student > Doctoral Student"=>1, "Researcher"=>1, "Student > Master"=>1, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Agricultural and Biological Sciences"=>2, "Medicine and Dentistry"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1806400"], "description"=>"<p>RAW264.7 cells were cultured for 4 hours with LPS (100 ng/mL) and 0.1, 0.5, 2.5 or 12.5 mg/mL MeOH extract (A), or 60, 300 or 1500 µM swertiamarin or gentiopicroside (B). TNF-α mRNA levels were measured by real-time PCR. Plotted values represent the mean value ± SD from four independent cultures. *p<0.05, **p<0.01.</p>", "links"=>[], "tags"=>["lps", "Murine Macrophages BackgroundGentian roots", "inhibition", "compound", "RAW 264.7 cells", "inos", "extract", "mrna", "gentiolactone", "expression", "Gentiana triflora", "nf", "mechanism", "cox", "tnf", "gentian roots"], "article_id"=>1251348, "categories"=>["Biological Sciences"], "users"=>["Hidetoshi Yamada", "Sayaka Kikuchi", "Tomoki Inui", "Hideyuki Takahashi", "Ken-ichi Kimura"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0113834.g001", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_MeOH_extract_from_gentian_roots_inhibits_LPS_induced_TNF_945_production_/1251348", "title"=>"MeOH extract from gentian roots inhibits LPS-induced TNF-α production.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-25 02:44:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/1806401"], "description"=>"<p>A, Structure of gentiolactone. The molecular formula of gentiolactone is C<sub>10</sub>H<sub>12</sub>O<sub>5</sub> and its monoisotopic mass is 212.068. B, RAW264.7 cells were seeded in 6-well culture plates (1×10<sup>6</sup> cells/well) and cultured with gentiolactone or helenalin for 24 hours. At the end of this period, the number of living cells in each well was counted.</p>", "links"=>[], "tags"=>["lps", "Murine Macrophages BackgroundGentian roots", "inhibition", "compound", "RAW 264.7 cells", "inos", "extract", "mrna", "gentiolactone", "expression", "Gentiana triflora", "nf", "mechanism", "cox", "tnf", "gentian roots"], "article_id"=>1251349, "categories"=>["Biological Sciences"], "users"=>["Hidetoshi Yamada", "Sayaka Kikuchi", "Tomoki Inui", "Hideyuki Takahashi", "Ken-ichi Kimura"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0113834.g002", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gentiolactone_and_cytotoxicity_of_gentiolactone_/1251349", "title"=>"Gentiolactone and cytotoxicity of gentiolactone.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-25 02:44:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/1806407"], "description"=>"<p>RAW264.7 cells were cultured for 4 hours with LPS (100 ng/mL) and 100, 500 or 1000 µM gentiolactone. The mRNA levels of TNF-α (A), iNOS (B) and Cox-2 (C) were measured by real-time PCR. (D) TNF-α protein levels were measured with an ELISA assay. Plotted values represent the mean value ± SD from four independent cultures. *p<0.05, **p<0.01. Helenalin was used as a positive control.</p>", "links"=>[], "tags"=>["lps", "Murine Macrophages BackgroundGentian roots", "inhibition", "compound", "RAW 264.7 cells", "inos", "extract", "mrna", "gentiolactone", "expression", "Gentiana triflora", "nf", "mechanism", "cox", "tnf", "gentian roots"], "article_id"=>1251351, "categories"=>["Biological Sciences"], "users"=>["Hidetoshi Yamada", "Sayaka Kikuchi", "Tomoki Inui", "Hideyuki Takahashi", "Ken-ichi Kimura"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0113834.g003", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gentiolactone_inhibits_LPS_induced_TNF_945_mRNA_expression_/1251351", "title"=>"Gentiolactone inhibits LPS-induced TNF-α mRNA expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-25 02:44:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/1806410"], "description"=>"<p>RAW264.7 cells were transfected with reporter plasmids and cultured with LPS (1 µg/mL) and gentiolactone (500 µM). At 12 hours after LPS stimulation, luciferase activity was measured. Plotted values represent the mean value ± SD from five independent cultures. Helenalin was used as a positive control.</p>", "links"=>[], "tags"=>["lps", "Murine Macrophages BackgroundGentian roots", "inhibition", "compound", "RAW 264.7 cells", "inos", "extract", "mrna", "gentiolactone", "expression", "Gentiana triflora", "nf", "mechanism", "cox", "tnf", "gentian roots"], "article_id"=>1251352, "categories"=>["Biological Sciences"], "users"=>["Hidetoshi Yamada", "Sayaka Kikuchi", "Tomoki Inui", "Hideyuki Takahashi", "Ken-ichi Kimura"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0113834.g004", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gentiolactone_suppresses_transcriptional_activity_of_NF_954_B_/1251352", "title"=>"Gentiolactone suppresses transcriptional activity of NF-κB.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-25 02:44:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/1806411"], "description"=>"<p>RAW264.7 cells were cultured with LPS (100 ng/mL) and gentiolactone (500 µM) for the indicated periods. Cell extracts from each group were examined by immunoblotting analysis using anti-IκBα antibody. Plotted values represent the mean value ± SD from four independent cultures. Helenalin was used as a positive control.</p>", "links"=>[], "tags"=>["lps", "Murine Macrophages BackgroundGentian roots", "inhibition", "compound", "RAW 264.7 cells", "inos", "extract", "mrna", "gentiolactone", "expression", "Gentiana triflora", "nf", "mechanism", "cox", "tnf", "gentian roots"], "article_id"=>1251353, "categories"=>["Biological Sciences"], "users"=>["Hidetoshi Yamada", "Sayaka Kikuchi", "Tomoki Inui", "Hideyuki Takahashi", "Ken-ichi Kimura"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0113834.g005", "stats"=>{"downloads"=>3, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gentiolactone_does_not_inhibit_I_954_B_degradation_induced_by_LPS_stimulation_/1251353", "title"=>"Gentiolactone does not inhibit IκB degradation induced by LPS stimulation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-25 02:44:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/1806413"], "description"=>"<p>RAW264.7 cells were cultured for 1 hour with LPS (1 µg/mL) and gentiolactone (500 µM). The cytoplasmic or nuclear extracts were examined by immunoblotting analysis using anti-p65/NF-κB, anti-α-Tubulin or anti-Lamin B1 antibodies. Plotted values represent the mean value ± SD from four independent cultures. Helenalin was used as a positive control.</p>", "links"=>[], "tags"=>["lps", "Murine Macrophages BackgroundGentian roots", "inhibition", "compound", "RAW 264.7 cells", "inos", "extract", "mrna", "gentiolactone", "expression", "Gentiana triflora", "nf", "mechanism", "cox", "tnf", "gentian roots"], "article_id"=>1251355, "categories"=>["Biological Sciences"], "users"=>["Hidetoshi Yamada", "Sayaka Kikuchi", "Tomoki Inui", "Hideyuki Takahashi", "Ken-ichi Kimura"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0113834.g006", "stats"=>{"downloads"=>3, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gentiolactone_does_not_inhibit_nuclear_transport_of_NF_954_B_/1251355", "title"=>"Gentiolactone does not inhibit nuclear transport of NF-κB.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-25 02:44:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/1806414"], "description"=>"<p>RAW264.7 cells were cultured for 1 hour with LPS (1 µg/mL) and gentiolactone (250, 500, 1000 µM). Nuclear proteins were extracted and incubated with biotinylated oligonucleotides containing a binding site for NF-κB. Resultant complexes were analyzed by EMSA. The bands indicated by the arrow were quantified. Plotted values represent the mean value ± SD from three independent cultures. Helenalin was used as a positive control.</p>", "links"=>[], "tags"=>["lps", "Murine Macrophages BackgroundGentian roots", "inhibition", "compound", "RAW 264.7 cells", "inos", "extract", "mrna", "gentiolactone", "expression", "Gentiana triflora", "nf", "mechanism", "cox", "tnf", "gentian roots"], "article_id"=>1251356, "categories"=>["Biological Sciences"], "users"=>["Hidetoshi Yamada", "Sayaka Kikuchi", "Tomoki Inui", "Hideyuki Takahashi", "Ken-ichi Kimura"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0113834.g007", "stats"=>{"downloads"=>4, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gentiolactone_does_not_inhibit_DNA_binding_of_NF_954_B_/1251356", "title"=>"Gentiolactone does not inhibit DNA binding of NF-κB.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-25 02:44:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/1806416", "https://ndownloader.figshare.com/files/1806417"], "description"=>"<div><p>Background</p><p>Gentian roots have been used as a herbal medicine because of their anti-inflammatory activities. However, the molecular mechanisms of these anti-inflammatory effects remain to be completely explained.</p><p>Methods and Findings</p><p>Here, we investigated anti-inflammatory effects of gentian roots and showed that root extracts from <i>Gentiana triflora</i> inhibited lipopolysaccharide (LPS)-induced expression of TNF-α in RAW264.7 cells. The extracts also contained swertiamarin and gentiopicroside, which are the major active compounds of gentian roots; however, neither compound had any effect on LPS-induced TNF-α production in our test system. We isolated gentiolactone as an inhibitor of TNF-α production from the extracts. Gentiolactone also inhibited LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (Cox-2) expression at the mRNA level. Moreover, gentiolactone suppressed NF-κB transcriptional activity without inhibition of IκB degradation or NF-κB nuclear transport.</p><p>Conclusions</p><p>Our results indicate that inhibition of TNF-α, iNOS and Cox-2 expression by gentiolactone is one of the mechanisms of the anti-inflammatory properties of gentian roots.</p></div>", "links"=>[], "tags"=>["lps", "Murine Macrophages BackgroundGentian roots", "inhibition", "compound", "RAW 264.7 cells", "inos", "extract", "mrna", "gentiolactone", "expression", "Gentiana triflora", "nf", "mechanism", "cox", "tnf", "gentian roots"], "article_id"=>1251358, "categories"=>["Biological Sciences"], "users"=>["Hidetoshi Yamada", "Sayaka Kikuchi", "Tomoki Inui", "Hideyuki Takahashi", "Ken-ichi Kimura"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0113834.s001", "https://dx.doi.org/10.1371/journal.pone.0113834.s002"], "stats"=>{"downloads"=>10, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Gentiolactone_a_Secoiridoid_Dilactone_from_Gentiana_triflora_Inhibits_TNF_iNOS_and_Cox_2_mRNA_Expression_and_Blocks_NF_B_Promoter_Activity_in_Murine_Macrophages/1251358", "title"=>"Gentiolactone, a Secoiridoid Dilactone from <i>Gentiana triflora</i>, Inhibits TNF-α, iNOS and Cox-2 mRNA Expression and Blocks NF-κB Promoter Activity in Murine Macrophages", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-11-25 02:44:48"}

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Relative Metric

{"start_date"=>"2014-01-01T00:00:00Z", "end_date"=>"2014-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Biochemistry", "average_usage"=>[282]}, {"subject_area"=>"/Biology and life sciences/Molecular biology", "average_usage"=>[292, 461]}, {"subject_area"=>"/Biology and life sciences/Organisms", "average_usage"=>[310]}, {"subject_area"=>"/Medicine and health sciences/Inflammatory diseases", "average_usage"=>[261, 415]}, {"subject_area"=>"/Medicine and health sciences/Pain management", "average_usage"=>[277, 451]}, {"subject_area"=>"/Physical sciences", "average_usage"=>[271]}]}
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