Ginkgetin, a Biflavone from Ginko biloba Leaves, Inhibits Cyclooxygenases-2 and 5-Lipoxygenase in Mouse Bone Marrow-Derived Mast Cells
Ginkgetin, a biflavone from Ginkgo biloba leaves, was previously reported to be a phospholipase A2 inhibitor and this compound showed the potent antiarthritic activity in rat adjuvant-induced arthritis as well as analgesic activity. This investigation was carried out to find effects on cyclooxygenas...
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| Veröffentlicht in: | Biological & pharmaceutical bulletin 2005, Vol.28(12), pp.2181-2184 |
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| creator | Son, Jong Keun Son, Min Jung Lee, Eunkyung Moon, Tae Chul Son, Kun Ho Kim, Cheorl-Ho Kim, Hyun Pyo Kang, Sam Sik Chang, Hyeun Wook |
| description | Ginkgetin, a biflavone from Ginkgo biloba leaves, was previously reported to be a phospholipase A2 inhibitor and this compound showed the potent antiarthritic activity in rat adjuvant-induced arthritis as well as analgesic activity. This investigation was carried out to find effects on cyclooxygenase-2 (COX-2) in vitro effect. Ginkgetin inhibits COX-2 dependent phases of prostaglandin D2 (PGD2) generation in bone marrow-derived mast cells (BMMC) in a concentration-dependent manner with IC50 values of 0.75 μM. Western blotting probed with specific anti-COX-2 antibodies showed that the decrease in quantity of the PGD2 product was accompanied by a decrease in the COX-2 protein level. In addition, this compound consistently inhibited the production of leukotriene C4 (LTC4) in a dose dependent manner, with an IC50 value of 0.33 μM. These results demonstrate that ginkgetin has a dual cyclooxygenase-2/5-lipoxygenase inhibitory activity. Furthermore, this compound also inhibited degranulation reaction in a dose dependent manner, with an IC50 value of 6.52 μM. Therefore, this compound might provide a basis for novel anti-inflammatory agents. |
| doi_str_mv | 10.1248/bpb.28.2181 |
| format | Article |
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This investigation was carried out to find effects on cyclooxygenase-2 (COX-2) in vitro effect. Ginkgetin inhibits COX-2 dependent phases of prostaglandin D2 (PGD2) generation in bone marrow-derived mast cells (BMMC) in a concentration-dependent manner with IC50 values of 0.75 μM. Western blotting probed with specific anti-COX-2 antibodies showed that the decrease in quantity of the PGD2 product was accompanied by a decrease in the COX-2 protein level. In addition, this compound consistently inhibited the production of leukotriene C4 (LTC4) in a dose dependent manner, with an IC50 value of 0.33 μM. These results demonstrate that ginkgetin has a dual cyclooxygenase-2/5-lipoxygenase inhibitory activity. Furthermore, this compound also inhibited degranulation reaction in a dose dependent manner, with an IC50 value of 6.52 μM. Therefore, this compound might provide a basis for novel anti-inflammatory agents.</description><identifier>ISSN: 0918-6158</identifier><identifier>EISSN: 1347-5215</identifier><identifier>DOI: 10.1248/bpb.28.2181</identifier><identifier>PMID: 16327145</identifier><language>eng</language><publisher>Japan: The Pharmaceutical Society of Japan</publisher><subject><![CDATA[5-lipoxygenase ; Animals ; Arachidonate 5-Lipoxygenase - metabolism ; beta-N-Acetylhexosaminidases - antagonists & inhibitors ; beta-N-Acetylhexosaminidases - metabolism ; biflavonoid ; Biflavonoids - chemistry ; Biflavonoids - isolation & purification ; Biflavonoids - pharmacology ; Bone Marrow Cells - drug effects ; Bone Marrow Cells - metabolism ; bone marrow-derived mast cell ; Cyclooxygenase 2 - genetics ; Cyclooxygenase 2 - metabolism ; Cyclooxygenase 2 Inhibitors - chemistry ; Cyclooxygenase 2 Inhibitors - pharmacology ; cyclooxygenase-2 ; Dose-Response Relationship, Drug ; Flavonoids - chemistry ; Flavonoids - isolation & purification ; Flavonoids - pharmacology ; ginkgetin ; Ginkgo biloba ; Interleukin-10 - pharmacology ; Leukotriene C4 - antagonists & inhibitors ; Leukotriene C4 - genetics ; Leukotriene C4 - metabolism ; Lipopolysaccharides - pharmacology ; Lipoxygenase Inhibitors ; Male ; Mast Cells - drug effects ; Mast Cells - metabolism ; Mast Cells - pathology ; Membrane Proteins - antagonists & inhibitors ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Mice ; Mice, Inbred BALB C ; Plant Leaves ; Prostaglandin D2 - antagonists & inhibitors ; Prostaglandin D2 - metabolism ; Up-Regulation]]></subject><ispartof>Biological and Pharmaceutical Bulletin, 2005, Vol.28(12), pp.2181-2184</ispartof><rights>2005 The Pharmaceutical Society of Japan</rights><rights>Copyright Japan Science and Technology Agency 2005</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c558t-6e79da6c6db05574b6fec985b37c6da2b5079ec962d702f56ca2a63a55e8295b3</citedby><cites>FETCH-LOGICAL-c558t-6e79da6c6db05574b6fec985b37c6da2b5079ec962d702f56ca2a63a55e8295b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1877,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16327145$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Son, Jong Keun</creatorcontrib><creatorcontrib>Son, Min Jung</creatorcontrib><creatorcontrib>Lee, Eunkyung</creatorcontrib><creatorcontrib>Moon, Tae Chul</creatorcontrib><creatorcontrib>Son, Kun Ho</creatorcontrib><creatorcontrib>Kim, Cheorl-Ho</creatorcontrib><creatorcontrib>Kim, Hyun Pyo</creatorcontrib><creatorcontrib>Kang, Sam Sik</creatorcontrib><creatorcontrib>Chang, Hyeun Wook</creatorcontrib><title>Ginkgetin, a Biflavone from Ginko biloba Leaves, Inhibits Cyclooxygenases-2 and 5-Lipoxygenase in Mouse Bone Marrow-Derived Mast Cells</title><title>Biological & pharmaceutical bulletin</title><addtitle>Biol Pharm Bull</addtitle><description>Ginkgetin, a biflavone from Ginkgo biloba leaves, was previously reported to be a phospholipase A2 inhibitor and this compound showed the potent antiarthritic activity in rat adjuvant-induced arthritis as well as analgesic activity. This investigation was carried out to find effects on cyclooxygenase-2 (COX-2) in vitro effect. Ginkgetin inhibits COX-2 dependent phases of prostaglandin D2 (PGD2) generation in bone marrow-derived mast cells (BMMC) in a concentration-dependent manner with IC50 values of 0.75 μM. Western blotting probed with specific anti-COX-2 antibodies showed that the decrease in quantity of the PGD2 product was accompanied by a decrease in the COX-2 protein level. In addition, this compound consistently inhibited the production of leukotriene C4 (LTC4) in a dose dependent manner, with an IC50 value of 0.33 μM. These results demonstrate that ginkgetin has a dual cyclooxygenase-2/5-lipoxygenase inhibitory activity. Furthermore, this compound also inhibited degranulation reaction in a dose dependent manner, with an IC50 value of 6.52 μM. Therefore, this compound might provide a basis for novel anti-inflammatory agents.</description><subject>5-lipoxygenase</subject><subject>Animals</subject><subject>Arachidonate 5-Lipoxygenase - metabolism</subject><subject>beta-N-Acetylhexosaminidases - antagonists & inhibitors</subject><subject>beta-N-Acetylhexosaminidases - metabolism</subject><subject>biflavonoid</subject><subject>Biflavonoids - chemistry</subject><subject>Biflavonoids - isolation & purification</subject><subject>Biflavonoids - pharmacology</subject><subject>Bone Marrow Cells - drug effects</subject><subject>Bone Marrow Cells - metabolism</subject><subject>bone marrow-derived mast cell</subject><subject>Cyclooxygenase 2 - genetics</subject><subject>Cyclooxygenase 2 - metabolism</subject><subject>Cyclooxygenase 2 Inhibitors - chemistry</subject><subject>Cyclooxygenase 2 Inhibitors - pharmacology</subject><subject>cyclooxygenase-2</subject><subject>Dose-Response Relationship, Drug</subject><subject>Flavonoids - chemistry</subject><subject>Flavonoids - isolation & purification</subject><subject>Flavonoids - pharmacology</subject><subject>ginkgetin</subject><subject>Ginkgo biloba</subject><subject>Interleukin-10 - pharmacology</subject><subject>Leukotriene C4 - antagonists & inhibitors</subject><subject>Leukotriene C4 - genetics</subject><subject>Leukotriene C4 - metabolism</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>Lipoxygenase Inhibitors</subject><subject>Male</subject><subject>Mast Cells - drug effects</subject><subject>Mast Cells - metabolism</subject><subject>Mast Cells - pathology</subject><subject>Membrane Proteins - antagonists & inhibitors</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Plant Leaves</subject><subject>Prostaglandin D2 - antagonists & inhibitors</subject><subject>Prostaglandin D2 - metabolism</subject><subject>Up-Regulation</subject><issn>0918-6158</issn><issn>1347-5215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc1uEzEUhS0EomlhxR5ZQmLTTvDP2ONZNgFKpVRsYG3Znjupw8QO9iSQF-C5cZQ0SGxs33M_HR3rIPSGkilltfpgN3bK1JRRRZ-hCeV1UwlGxXM0IS1VlaRCXaDLnFeEkIYw_hJdUMlZQ2sxQX_ufPixhNGHG2zwzPeD2cUAuE9xjQ-7iK0fojV4AWYH-Qbfh0dv_ZjxfO-GGH_vlxBMhlwxbEKHRbXwm7OKfcAPcVses4Prg0kp_qo-QvI76MqYRzyHYciv0IveDBlen-4r9P3zp2_zL9Xi6939_HZROSHUWElo2s5IJztLhGhqK3twrRKWN0UzzArStEWRrCs_7YV0hhnJjRCgWFuwK_T-6LtJ8ecW8qjXPruSwAQoMbVUStS8bQr47j9wFbcplGya1nXLheKKFur6SLkUc07Q603ya5P2mhJ9KEeXcjRT-lBOod-ePLd2Dd0_9tRGAWZHYJVHs4QzYNLo3QBPZpQ9ncX1vHSPJmkI_C_vq6HT</recordid><startdate>20051201</startdate><enddate>20051201</enddate><creator>Son, Jong Keun</creator><creator>Son, Min Jung</creator><creator>Lee, Eunkyung</creator><creator>Moon, Tae Chul</creator><creator>Son, Kun Ho</creator><creator>Kim, Cheorl-Ho</creator><creator>Kim, Hyun Pyo</creator><creator>Kang, Sam Sik</creator><creator>Chang, Hyeun Wook</creator><general>The Pharmaceutical Society of Japan</general><general>Japan Science and Technology Agency</general><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>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20051201</creationdate><title>Ginkgetin, a Biflavone from Ginko biloba Leaves, Inhibits Cyclooxygenases-2 and 5-Lipoxygenase in Mouse Bone Marrow-Derived Mast Cells</title><author>Son, Jong Keun ; Son, Min Jung ; Lee, Eunkyung ; Moon, Tae Chul ; Son, Kun Ho ; Kim, Cheorl-Ho ; Kim, Hyun Pyo ; Kang, Sam Sik ; Chang, Hyeun Wook</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c558t-6e79da6c6db05574b6fec985b37c6da2b5079ec962d702f56ca2a63a55e8295b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>5-lipoxygenase</topic><topic>Animals</topic><topic>Arachidonate 5-Lipoxygenase - metabolism</topic><topic>beta-N-Acetylhexosaminidases - antagonists & inhibitors</topic><topic>beta-N-Acetylhexosaminidases - metabolism</topic><topic>biflavonoid</topic><topic>Biflavonoids - chemistry</topic><topic>Biflavonoids - isolation & purification</topic><topic>Biflavonoids - pharmacology</topic><topic>Bone Marrow Cells - drug effects</topic><topic>Bone Marrow Cells - metabolism</topic><topic>bone marrow-derived mast cell</topic><topic>Cyclooxygenase 2 - genetics</topic><topic>Cyclooxygenase 2 - metabolism</topic><topic>Cyclooxygenase 2 Inhibitors - chemistry</topic><topic>Cyclooxygenase 2 Inhibitors - pharmacology</topic><topic>cyclooxygenase-2</topic><topic>Dose-Response Relationship, Drug</topic><topic>Flavonoids - chemistry</topic><topic>Flavonoids - isolation & purification</topic><topic>Flavonoids - pharmacology</topic><topic>ginkgetin</topic><topic>Ginkgo biloba</topic><topic>Interleukin-10 - pharmacology</topic><topic>Leukotriene C4 - antagonists & inhibitors</topic><topic>Leukotriene C4 - genetics</topic><topic>Leukotriene C4 - metabolism</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>Lipoxygenase Inhibitors</topic><topic>Male</topic><topic>Mast Cells - drug effects</topic><topic>Mast Cells - metabolism</topic><topic>Mast Cells - pathology</topic><topic>Membrane Proteins - antagonists & inhibitors</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Plant Leaves</topic><topic>Prostaglandin D2 - antagonists & inhibitors</topic><topic>Prostaglandin D2 - metabolism</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Son, Jong Keun</creatorcontrib><creatorcontrib>Son, Min Jung</creatorcontrib><creatorcontrib>Lee, Eunkyung</creatorcontrib><creatorcontrib>Moon, Tae Chul</creatorcontrib><creatorcontrib>Son, Kun Ho</creatorcontrib><creatorcontrib>Kim, Cheorl-Ho</creatorcontrib><creatorcontrib>Kim, Hyun Pyo</creatorcontrib><creatorcontrib>Kang, Sam Sik</creatorcontrib><creatorcontrib>Chang, Hyeun Wook</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biological & pharmaceutical bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Son, Jong Keun</au><au>Son, Min Jung</au><au>Lee, Eunkyung</au><au>Moon, Tae Chul</au><au>Son, Kun Ho</au><au>Kim, Cheorl-Ho</au><au>Kim, Hyun Pyo</au><au>Kang, Sam Sik</au><au>Chang, Hyeun Wook</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ginkgetin, a Biflavone from Ginko biloba Leaves, Inhibits Cyclooxygenases-2 and 5-Lipoxygenase in Mouse Bone Marrow-Derived Mast Cells</atitle><jtitle>Biological & pharmaceutical bulletin</jtitle><addtitle>Biol Pharm Bull</addtitle><date>2005-12-01</date><risdate>2005</risdate><volume>28</volume><issue>12</issue><spage>2181</spage><epage>2184</epage><pages>2181-2184</pages><issn>0918-6158</issn><eissn>1347-5215</eissn><abstract>Ginkgetin, a biflavone from Ginkgo biloba leaves, was previously reported to be a phospholipase A2 inhibitor and this compound showed the potent antiarthritic activity in rat adjuvant-induced arthritis as well as analgesic activity. This investigation was carried out to find effects on cyclooxygenase-2 (COX-2) in vitro effect. Ginkgetin inhibits COX-2 dependent phases of prostaglandin D2 (PGD2) generation in bone marrow-derived mast cells (BMMC) in a concentration-dependent manner with IC50 values of 0.75 μM. Western blotting probed with specific anti-COX-2 antibodies showed that the decrease in quantity of the PGD2 product was accompanied by a decrease in the COX-2 protein level. In addition, this compound consistently inhibited the production of leukotriene C4 (LTC4) in a dose dependent manner, with an IC50 value of 0.33 μM. These results demonstrate that ginkgetin has a dual cyclooxygenase-2/5-lipoxygenase inhibitory activity. Furthermore, this compound also inhibited degranulation reaction in a dose dependent manner, with an IC50 value of 6.52 μM. Therefore, this compound might provide a basis for novel anti-inflammatory agents.</abstract><cop>Japan</cop><pub>The Pharmaceutical Society of Japan</pub><pmid>16327145</pmid><doi>10.1248/bpb.28.2181</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 5-lipoxygenase Animals Arachidonate 5-Lipoxygenase - metabolism beta-N-Acetylhexosaminidases - antagonists & inhibitors beta-N-Acetylhexosaminidases - metabolism biflavonoid Biflavonoids - chemistry Biflavonoids - isolation & purification Biflavonoids - pharmacology Bone Marrow Cells - drug effects Bone Marrow Cells - metabolism bone marrow-derived mast cell Cyclooxygenase 2 - genetics Cyclooxygenase 2 - metabolism Cyclooxygenase 2 Inhibitors - chemistry Cyclooxygenase 2 Inhibitors - pharmacology cyclooxygenase-2 Dose-Response Relationship, Drug Flavonoids - chemistry Flavonoids - isolation & purification Flavonoids - pharmacology ginkgetin Ginkgo biloba Interleukin-10 - pharmacology Leukotriene C4 - antagonists & inhibitors Leukotriene C4 - genetics Leukotriene C4 - metabolism Lipopolysaccharides - pharmacology Lipoxygenase Inhibitors Male Mast Cells - drug effects Mast Cells - metabolism Mast Cells - pathology Membrane Proteins - antagonists & inhibitors Membrane Proteins - genetics Membrane Proteins - metabolism Mice Mice, Inbred BALB C Plant Leaves Prostaglandin D2 - antagonists & inhibitors Prostaglandin D2 - metabolism Up-Regulation |
| title | Ginkgetin, a Biflavone from Ginko biloba Leaves, Inhibits Cyclooxygenases-2 and 5-Lipoxygenase in Mouse Bone Marrow-Derived Mast Cells |
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