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Neuroprotective and anti-inflammatory effects of mollugin via up-regulation of heme oxygenase-1 in mouse hippocampal and microglial cells
Mollugin, a bioactive phytochemical isolated from Rubia cordifolia L. (Rubiaceae), exhibits antimutagenic activity, antitumor activity, antiviral activity, and inhibitory activity in arachidonic acid- and collagen-induced platelet aggregation. In this study, we investigated the effects of mollugin a...
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| Published in: | European journal of pharmacology 2011-03, Vol.654 (3), p.226-234 |
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| container_end_page | 234 |
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| container_title | European journal of pharmacology |
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| creator | Jeong, Gil-Saeng Lee, Dong-Sung Kim, Dong-Chun Jahng, Yurngdong Son, Jong-Keun Lee, Seung-Ho Kim, Youn-Chul |
| description | Mollugin, a bioactive phytochemical isolated from
Rubia cordifolia L. (Rubiaceae), exhibits antimutagenic activity, antitumor activity, antiviral activity, and inhibitory activity in arachidonic acid- and collagen-induced platelet aggregation. In this study, we investigated the effects of mollugin as a neuroprotective agent in glutamate-induced neurotoxicity in the mouse hippocampal HT22 cell line and as an anti-inflammatory agent in lipopolysaccharide-induced microglial activation in BV2 cells. Mollugin showed potent neuroprotective effects against glutamate-induced neurotoxicity and reactive oxygen species generation in mouse hippocampal HT22 cells. In addition, the anti-inflammatory effects of mollugin were demonstrated by the suppression of pro-inflammatory mediators, including pro-inflammatory enzymes (inducible nitric oxide synthase and cyclooxygenase-2) and cytokines (tumor necrosis factor-α and interleukin-6). Furthermore, we found that the neuroprotective and anti-inflammatory effects of mollugin were linked to the up-regulation of the expression of heme oxygenase (HO)-1 and the activity of HO in HT22 and BV2 cells. In addition, the effects of mollugin resulted in the nuclear accumulation of nuclear factor-E2-related factor 2 (Nrf2) in HT22 and BV2 cells. Furthermore, mollugin also activated the p38 mitogen-activated protein kinase (MAPK) pathway both in HT22 and BV2 cells. These results suggest that mollugin may be a promising candidate for the treatment of neurodegenerative diseases related to neuroinflammation. |
| doi_str_mv | 10.1016/j.ejphar.2010.12.027 |
| format | article |
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Rubia cordifolia L. (Rubiaceae), exhibits antimutagenic activity, antitumor activity, antiviral activity, and inhibitory activity in arachidonic acid- and collagen-induced platelet aggregation. In this study, we investigated the effects of mollugin as a neuroprotective agent in glutamate-induced neurotoxicity in the mouse hippocampal HT22 cell line and as an anti-inflammatory agent in lipopolysaccharide-induced microglial activation in BV2 cells. Mollugin showed potent neuroprotective effects against glutamate-induced neurotoxicity and reactive oxygen species generation in mouse hippocampal HT22 cells. In addition, the anti-inflammatory effects of mollugin were demonstrated by the suppression of pro-inflammatory mediators, including pro-inflammatory enzymes (inducible nitric oxide synthase and cyclooxygenase-2) and cytokines (tumor necrosis factor-α and interleukin-6). Furthermore, we found that the neuroprotective and anti-inflammatory effects of mollugin were linked to the up-regulation of the expression of heme oxygenase (HO)-1 and the activity of HO in HT22 and BV2 cells. In addition, the effects of mollugin resulted in the nuclear accumulation of nuclear factor-E2-related factor 2 (Nrf2) in HT22 and BV2 cells. Furthermore, mollugin also activated the p38 mitogen-activated protein kinase (MAPK) pathway both in HT22 and BV2 cells. These results suggest that mollugin may be a promising candidate for the treatment of neurodegenerative diseases related to neuroinflammation.</description><identifier>ISSN: 0014-2999</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/j.ejphar.2010.12.027</identifier><identifier>PMID: 21236252</identifier><identifier>CODEN: EJPHAZ</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Active Transport, Cell Nucleus - drug effects ; Animals ; Anti-inflammation ; anti-inflammatory activity ; anti-inflammatory agents ; Anti-Inflammatory Agents - pharmacology ; anticarcinogenic activity ; antimutagenic activity ; Antioxidants - pharmacology ; antiviral properties ; Biological and medical sciences ; BV2 ; Cell Line ; Cell Nucleus - drug effects ; Cell Nucleus - metabolism ; Cytokines - metabolism ; Enzyme Induction - drug effects ; Gene Expression Regulation, Enzymologic - drug effects ; Glutamic Acid - toxicity ; heme oxygenase (biliverdin-producing) ; Heme oxygenase (HO)-1 ; Heme Oxygenase-1 - biosynthesis ; Heme Oxygenase-1 - metabolism ; Hippocampus - cytology ; Hippocampus - drug effects ; Hippocampus - enzymology ; Hippocampus - metabolism ; HT22 ; inducible nitric oxide synthase ; interleukin-6 ; Lipopolysaccharides - pharmacology ; MAP Kinase Signaling System - drug effects ; Medical sciences ; Mice ; Microglia - cytology ; Microglia - drug effects ; Microglia - enzymology ; Microglia - metabolism ; mitogen-activated protein kinase ; Mollugin ; neurodegenerative diseases ; Neuropharmacology ; Neuroprotection ; Neuroprotective agent ; Neuroprotective Agents - pharmacology ; neuroprotective effect ; neurotoxicity ; NF-E2-Related Factor 2 - metabolism ; Oxidative Stress - drug effects ; p38 Mitogen-Activated Protein Kinases - metabolism ; Pharmacology. Drug treatments ; platelet aggregation ; prostaglandin synthase ; Pyrans - pharmacology ; reactive oxygen species ; Reactive Oxygen Species - metabolism ; Rubia ; Rubia cordifolia ; Rubiaceae ; tumor necrosis factor-alpha ; Up-Regulation - drug effects</subject><ispartof>European journal of pharmacology, 2011-03, Vol.654 (3), p.226-234</ispartof><rights>2011</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011. Published by Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c513t-98fb3e8ba07bbf9f27e84ee5af649b144195c35d3ff486214251f7e806394ac93</citedby><cites>FETCH-LOGICAL-c513t-98fb3e8ba07bbf9f27e84ee5af649b144195c35d3ff486214251f7e806394ac93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23870534$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21236252$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jeong, Gil-Saeng</creatorcontrib><creatorcontrib>Lee, Dong-Sung</creatorcontrib><creatorcontrib>Kim, Dong-Chun</creatorcontrib><creatorcontrib>Jahng, Yurngdong</creatorcontrib><creatorcontrib>Son, Jong-Keun</creatorcontrib><creatorcontrib>Lee, Seung-Ho</creatorcontrib><creatorcontrib>Kim, Youn-Chul</creatorcontrib><title>Neuroprotective and anti-inflammatory effects of mollugin via up-regulation of heme oxygenase-1 in mouse hippocampal and microglial cells</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>Mollugin, a bioactive phytochemical isolated from
Rubia cordifolia L. (Rubiaceae), exhibits antimutagenic activity, antitumor activity, antiviral activity, and inhibitory activity in arachidonic acid- and collagen-induced platelet aggregation. In this study, we investigated the effects of mollugin as a neuroprotective agent in glutamate-induced neurotoxicity in the mouse hippocampal HT22 cell line and as an anti-inflammatory agent in lipopolysaccharide-induced microglial activation in BV2 cells. Mollugin showed potent neuroprotective effects against glutamate-induced neurotoxicity and reactive oxygen species generation in mouse hippocampal HT22 cells. In addition, the anti-inflammatory effects of mollugin were demonstrated by the suppression of pro-inflammatory mediators, including pro-inflammatory enzymes (inducible nitric oxide synthase and cyclooxygenase-2) and cytokines (tumor necrosis factor-α and interleukin-6). Furthermore, we found that the neuroprotective and anti-inflammatory effects of mollugin were linked to the up-regulation of the expression of heme oxygenase (HO)-1 and the activity of HO in HT22 and BV2 cells. In addition, the effects of mollugin resulted in the nuclear accumulation of nuclear factor-E2-related factor 2 (Nrf2) in HT22 and BV2 cells. Furthermore, mollugin also activated the p38 mitogen-activated protein kinase (MAPK) pathway both in HT22 and BV2 cells. These results suggest that mollugin may be a promising candidate for the treatment of neurodegenerative diseases related to neuroinflammation.</description><subject>Active Transport, Cell Nucleus - drug effects</subject><subject>Animals</subject><subject>Anti-inflammation</subject><subject>anti-inflammatory activity</subject><subject>anti-inflammatory agents</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>anticarcinogenic activity</subject><subject>antimutagenic activity</subject><subject>Antioxidants - pharmacology</subject><subject>antiviral properties</subject><subject>Biological and medical sciences</subject><subject>BV2</subject><subject>Cell Line</subject><subject>Cell Nucleus - drug effects</subject><subject>Cell Nucleus - metabolism</subject><subject>Cytokines - metabolism</subject><subject>Enzyme Induction - drug effects</subject><subject>Gene Expression Regulation, Enzymologic - drug effects</subject><subject>Glutamic Acid - toxicity</subject><subject>heme oxygenase (biliverdin-producing)</subject><subject>Heme oxygenase (HO)-1</subject><subject>Heme Oxygenase-1 - biosynthesis</subject><subject>Heme Oxygenase-1 - metabolism</subject><subject>Hippocampus - cytology</subject><subject>Hippocampus - drug effects</subject><subject>Hippocampus - enzymology</subject><subject>Hippocampus - metabolism</subject><subject>HT22</subject><subject>inducible nitric oxide synthase</subject><subject>interleukin-6</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Microglia - cytology</subject><subject>Microglia - drug effects</subject><subject>Microglia - enzymology</subject><subject>Microglia - metabolism</subject><subject>mitogen-activated protein kinase</subject><subject>Mollugin</subject><subject>neurodegenerative diseases</subject><subject>Neuropharmacology</subject><subject>Neuroprotection</subject><subject>Neuroprotective agent</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>neuroprotective effect</subject><subject>neurotoxicity</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>Oxidative Stress - drug effects</subject><subject>p38 Mitogen-Activated Protein Kinases - metabolism</subject><subject>Pharmacology. Drug treatments</subject><subject>platelet aggregation</subject><subject>prostaglandin synthase</subject><subject>Pyrans - pharmacology</subject><subject>reactive oxygen species</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Rubia</subject><subject>Rubia cordifolia</subject><subject>Rubiaceae</subject><subject>tumor necrosis factor-alpha</subject><subject>Up-Regulation - drug effects</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><recordid>eNp9kcuO1DAQRS0EYpqBP0CQDWKVxs8k3iCNRrykESxg1pbjlNNuOXGwkxb9Cfw1Dmlgx8Ky7Drle10XoecE7wkm1ZvjHo7TQcc9xesV3WNaP0A70tSyxDWhD9EOY8JLKqW8Qk9SOmKMhaTiMbqihLKKCrpDPz_DEsMUwwxmdico9NjlNbvSjdbrYdBziOcCrM31VARbDMH7pXdjcXK6WKYyQr94PbswrtUDDFCEH-ceRp2gJEUGh7AkKA5umoLRw6T9b5HBmRh67_LRgPfpKXpktU_w7LJfo_v3777dfizvvnz4dHtzVxpB2FzKxrYMmlbjum2ttLSGhgMIbSsuW8I5kcIw0TFreVNRwqkgNjO4YpJrI9k1er29mz_9fYE0q8Gl1YEeIRtVMg-PS0FZJvlGZqMpRbBqim7Q8awIVmsG6qi2DNSagSJU5Qxy24uLwNIO0P1t-jP0DLy6ADoZ7W3Uo3HpH8eaGgvGM_dy46wOSvcxM_dfs5LIQXKMqcjE242APLCTg6iScTAa6FzMeakuuP97_QU5TbJh</recordid><startdate>20110311</startdate><enddate>20110311</enddate><creator>Jeong, Gil-Saeng</creator><creator>Lee, Dong-Sung</creator><creator>Kim, Dong-Chun</creator><creator>Jahng, Yurngdong</creator><creator>Son, Jong-Keun</creator><creator>Lee, Seung-Ho</creator><creator>Kim, Youn-Chul</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>FBQ</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope></search><sort><creationdate>20110311</creationdate><title>Neuroprotective and anti-inflammatory effects of mollugin via up-regulation of heme oxygenase-1 in mouse hippocampal and microglial cells</title><author>Jeong, Gil-Saeng ; Lee, Dong-Sung ; Kim, Dong-Chun ; Jahng, Yurngdong ; Son, Jong-Keun ; Lee, Seung-Ho ; Kim, Youn-Chul</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c513t-98fb3e8ba07bbf9f27e84ee5af649b144195c35d3ff486214251f7e806394ac93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Active Transport, Cell Nucleus - drug effects</topic><topic>Animals</topic><topic>Anti-inflammation</topic><topic>anti-inflammatory activity</topic><topic>anti-inflammatory agents</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>anticarcinogenic activity</topic><topic>antimutagenic activity</topic><topic>Antioxidants - pharmacology</topic><topic>antiviral properties</topic><topic>Biological and medical sciences</topic><topic>BV2</topic><topic>Cell Line</topic><topic>Cell Nucleus - drug effects</topic><topic>Cell Nucleus - metabolism</topic><topic>Cytokines - metabolism</topic><topic>Enzyme Induction - drug effects</topic><topic>Gene Expression Regulation, Enzymologic - drug effects</topic><topic>Glutamic Acid - toxicity</topic><topic>heme oxygenase (biliverdin-producing)</topic><topic>Heme oxygenase (HO)-1</topic><topic>Heme Oxygenase-1 - biosynthesis</topic><topic>Heme Oxygenase-1 - metabolism</topic><topic>Hippocampus - cytology</topic><topic>Hippocampus - drug effects</topic><topic>Hippocampus - enzymology</topic><topic>Hippocampus - metabolism</topic><topic>HT22</topic><topic>inducible nitric oxide synthase</topic><topic>interleukin-6</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Microglia - cytology</topic><topic>Microglia - drug effects</topic><topic>Microglia - enzymology</topic><topic>Microglia - metabolism</topic><topic>mitogen-activated protein kinase</topic><topic>Mollugin</topic><topic>neurodegenerative diseases</topic><topic>Neuropharmacology</topic><topic>Neuroprotection</topic><topic>Neuroprotective agent</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>neuroprotective effect</topic><topic>neurotoxicity</topic><topic>NF-E2-Related Factor 2 - metabolism</topic><topic>Oxidative Stress - drug effects</topic><topic>p38 Mitogen-Activated Protein Kinases - metabolism</topic><topic>Pharmacology. Drug treatments</topic><topic>platelet aggregation</topic><topic>prostaglandin synthase</topic><topic>Pyrans - pharmacology</topic><topic>reactive oxygen species</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Rubia</topic><topic>Rubia cordifolia</topic><topic>Rubiaceae</topic><topic>tumor necrosis factor-alpha</topic><topic>Up-Regulation - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jeong, Gil-Saeng</creatorcontrib><creatorcontrib>Lee, Dong-Sung</creatorcontrib><creatorcontrib>Kim, Dong-Chun</creatorcontrib><creatorcontrib>Jahng, Yurngdong</creatorcontrib><creatorcontrib>Son, Jong-Keun</creatorcontrib><creatorcontrib>Lee, Seung-Ho</creatorcontrib><creatorcontrib>Kim, Youn-Chul</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jeong, Gil-Saeng</au><au>Lee, Dong-Sung</au><au>Kim, Dong-Chun</au><au>Jahng, Yurngdong</au><au>Son, Jong-Keun</au><au>Lee, Seung-Ho</au><au>Kim, Youn-Chul</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neuroprotective and anti-inflammatory effects of mollugin via up-regulation of heme oxygenase-1 in mouse hippocampal and microglial cells</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2011-03-11</date><risdate>2011</risdate><volume>654</volume><issue>3</issue><spage>226</spage><epage>234</epage><pages>226-234</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><coden>EJPHAZ</coden><notes>http://dx.doi.org/10.1016/j.ejphar.2010.12.027</notes><notes>ObjectType-Article-2</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-1</notes><notes>content type line 23</notes><abstract>Mollugin, a bioactive phytochemical isolated from
Rubia cordifolia L. (Rubiaceae), exhibits antimutagenic activity, antitumor activity, antiviral activity, and inhibitory activity in arachidonic acid- and collagen-induced platelet aggregation. In this study, we investigated the effects of mollugin as a neuroprotective agent in glutamate-induced neurotoxicity in the mouse hippocampal HT22 cell line and as an anti-inflammatory agent in lipopolysaccharide-induced microglial activation in BV2 cells. Mollugin showed potent neuroprotective effects against glutamate-induced neurotoxicity and reactive oxygen species generation in mouse hippocampal HT22 cells. In addition, the anti-inflammatory effects of mollugin were demonstrated by the suppression of pro-inflammatory mediators, including pro-inflammatory enzymes (inducible nitric oxide synthase and cyclooxygenase-2) and cytokines (tumor necrosis factor-α and interleukin-6). Furthermore, we found that the neuroprotective and anti-inflammatory effects of mollugin were linked to the up-regulation of the expression of heme oxygenase (HO)-1 and the activity of HO in HT22 and BV2 cells. In addition, the effects of mollugin resulted in the nuclear accumulation of nuclear factor-E2-related factor 2 (Nrf2) in HT22 and BV2 cells. Furthermore, mollugin also activated the p38 mitogen-activated protein kinase (MAPK) pathway both in HT22 and BV2 cells. These results suggest that mollugin may be a promising candidate for the treatment of neurodegenerative diseases related to neuroinflammation.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>21236252</pmid><doi>10.1016/j.ejphar.2010.12.027</doi><tpages>9</tpages></addata></record> |
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| ispartof | European journal of pharmacology, 2011-03, Vol.654 (3), p.226-234 |
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| subjects | Active Transport, Cell Nucleus - drug effects Animals Anti-inflammation anti-inflammatory activity anti-inflammatory agents Anti-Inflammatory Agents - pharmacology anticarcinogenic activity antimutagenic activity Antioxidants - pharmacology antiviral properties Biological and medical sciences BV2 Cell Line Cell Nucleus - drug effects Cell Nucleus - metabolism Cytokines - metabolism Enzyme Induction - drug effects Gene Expression Regulation, Enzymologic - drug effects Glutamic Acid - toxicity heme oxygenase (biliverdin-producing) Heme oxygenase (HO)-1 Heme Oxygenase-1 - biosynthesis Heme Oxygenase-1 - metabolism Hippocampus - cytology Hippocampus - drug effects Hippocampus - enzymology Hippocampus - metabolism HT22 inducible nitric oxide synthase interleukin-6 Lipopolysaccharides - pharmacology MAP Kinase Signaling System - drug effects Medical sciences Mice Microglia - cytology Microglia - drug effects Microglia - enzymology Microglia - metabolism mitogen-activated protein kinase Mollugin neurodegenerative diseases Neuropharmacology Neuroprotection Neuroprotective agent Neuroprotective Agents - pharmacology neuroprotective effect neurotoxicity NF-E2-Related Factor 2 - metabolism Oxidative Stress - drug effects p38 Mitogen-Activated Protein Kinases - metabolism Pharmacology. Drug treatments platelet aggregation prostaglandin synthase Pyrans - pharmacology reactive oxygen species Reactive Oxygen Species - metabolism Rubia Rubia cordifolia Rubiaceae tumor necrosis factor-alpha Up-Regulation - drug effects |
| title | Neuroprotective and anti-inflammatory effects of mollugin via up-regulation of heme oxygenase-1 in mouse hippocampal and microglial cells |
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