The wound-healing effect of 7,3′,4′-trimethoxyflavone through increased levels of prostaglandin E2 by 15-hydroxyprostaglandin dehydrogenase inhibition
Objective To find an inhibitor of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) that rapidly metabolises Prostaglandin E 2 (PGE 2 ) as a mediator of wound healing, we examined seven flavonoids for this role. Results 7,3′,4′-Trimethoxyflavone (TMF) had the lowest IC 50 value of 0.34 µM for 15-PGDH...
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Veröffentlicht in: | Biotechnology letters 2017-10, Vol.39 (10), p.1575-1582 |
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creator | Sun, Kyung Hoon Karna, Sandeep Moon, Young-Sook Cho, Hoon Choi, Cheol-Hee |
description | Objective
To find an inhibitor of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) that rapidly metabolises Prostaglandin E
2
(PGE
2
) as a mediator of wound healing, we examined seven flavonoids for this role.
Results
7,3′,4′-Trimethoxyflavone (TMF) had the lowest IC
50
value of 0.34 µM for 15-PGDH inhibition but >400 µM for cytotoxicity, indicating a high therapeutic index. TMF elevated PGE
2
levels in a concentration-dependent manner in both A549 lung cancer and HaCaT cells. It also significantly increased mRNA expression of multidrug resistance-associated protein 4 (MRP4) and of prostaglandin transporter (PGT) slightly in HaCaT cells. In addition, TMF facilitated in vitro wound healing in a HaCaT scratch model, which was completely inhibited by adding both 15-PGDH and NAD
+
as cofactor, confirming the involvement of PGE
2
in its wound healing effect.
Conclusion
TMF with a high therapeutic index can facilitate wound healing through PGE
2
elevation by 15-PGDH inhibition. |
doi_str_mv | 10.1007/s10529-017-2386-2 |
format | Article |
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To find an inhibitor of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) that rapidly metabolises Prostaglandin E
2
(PGE
2
) as a mediator of wound healing, we examined seven flavonoids for this role.
Results
7,3′,4′-Trimethoxyflavone (TMF) had the lowest IC
50
value of 0.34 µM for 15-PGDH inhibition but >400 µM for cytotoxicity, indicating a high therapeutic index. TMF elevated PGE
2
levels in a concentration-dependent manner in both A549 lung cancer and HaCaT cells. It also significantly increased mRNA expression of multidrug resistance-associated protein 4 (MRP4) and of prostaglandin transporter (PGT) slightly in HaCaT cells. In addition, TMF facilitated in vitro wound healing in a HaCaT scratch model, which was completely inhibited by adding both 15-PGDH and NAD
+
as cofactor, confirming the involvement of PGE
2
in its wound healing effect.
Conclusion
TMF with a high therapeutic index can facilitate wound healing through PGE
2
elevation by 15-PGDH inhibition.</description><identifier>ISSN: 0141-5492</identifier><identifier>EISSN: 1573-6776</identifier><identifier>DOI: 10.1007/s10529-017-2386-2</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Applied Microbiology ; Biochemistry ; Biomedical and Life Sciences ; Biotechnology ; cytotoxicity ; flavonoids ; gene expression ; Life Sciences ; lung neoplasms ; Microbiology ; Original Research Paper ; oxidoreductases ; prostaglandins ; therapeutics</subject><ispartof>Biotechnology letters, 2017-10, Vol.39 (10), p.1575-1582</ispartof><rights>Springer Science+Business Media B.V. 2017</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c354t-f3a69c653a696e703f5ced3506346a63b93a1623a92649bfd165721e43124ac73</citedby><cites>FETCH-LOGICAL-c354t-f3a69c653a696e703f5ced3506346a63b93a1623a92649bfd165721e43124ac73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10529-017-2386-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10529-017-2386-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids></links><search><creatorcontrib>Sun, Kyung Hoon</creatorcontrib><creatorcontrib>Karna, Sandeep</creatorcontrib><creatorcontrib>Moon, Young-Sook</creatorcontrib><creatorcontrib>Cho, Hoon</creatorcontrib><creatorcontrib>Choi, Cheol-Hee</creatorcontrib><title>The wound-healing effect of 7,3′,4′-trimethoxyflavone through increased levels of prostaglandin E2 by 15-hydroxyprostaglandin dehydrogenase inhibition</title><title>Biotechnology letters</title><addtitle>Biotechnol Lett</addtitle><description>Objective
To find an inhibitor of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) that rapidly metabolises Prostaglandin E
2
(PGE
2
) as a mediator of wound healing, we examined seven flavonoids for this role.
Results
7,3′,4′-Trimethoxyflavone (TMF) had the lowest IC
50
value of 0.34 µM for 15-PGDH inhibition but >400 µM for cytotoxicity, indicating a high therapeutic index. TMF elevated PGE
2
levels in a concentration-dependent manner in both A549 lung cancer and HaCaT cells. It also significantly increased mRNA expression of multidrug resistance-associated protein 4 (MRP4) and of prostaglandin transporter (PGT) slightly in HaCaT cells. In addition, TMF facilitated in vitro wound healing in a HaCaT scratch model, which was completely inhibited by adding both 15-PGDH and NAD
+
as cofactor, confirming the involvement of PGE
2
in its wound healing effect.
Conclusion
TMF with a high therapeutic index can facilitate wound healing through PGE
2
elevation by 15-PGDH inhibition.</description><subject>Applied Microbiology</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biotechnology</subject><subject>cytotoxicity</subject><subject>flavonoids</subject><subject>gene expression</subject><subject>Life Sciences</subject><subject>lung neoplasms</subject><subject>Microbiology</subject><subject>Original Research Paper</subject><subject>oxidoreductases</subject><subject>prostaglandins</subject><subject>therapeutics</subject><issn>0141-5492</issn><issn>1573-6776</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNqFUctuFDEQtBBILAsfwM1HDjFx-7k-oigEpEhcwtnyzrRnJprYwZ4J7C3fwWfwSXwJXpYLF7h0S91VpeouQl4Dfwuc2_MKXAvHOFgm5M4w8YRsQFvJjLXmKdlwUMC0cuI5eVHrLefcWW435PvNiPRrXlPPRgzzlAaKMWK30BypPZM_H3-cqVbYUqY7XMb87RDn8JAT0mUseR1GOqWuYKjY0xkfcK5H5n3JdQnDHFI_JXop6P5AQbPx0Jem8Pe2x9_jAVMTaWrjtJ-WKaeX5FkMc8VXf_qWfH5_eXPxgV1_uvp48e6adVKrhUUZjOuMPjaDlsuoO-yl5kYqE4zcOxnACBmcMMrtYw9GWwGoJAgVOiu35M1Jt9n6smJd_N1UO5ybPcxr9aI9Syuz0-6_UHCgpRIgdw0KJ2jXjq0Fo79vHwzl4IH7Y2T-FJlvkfljZK1siThxasOmAYu_zWtJ7fh_kH4Bq7Cc7g</recordid><startdate>20171001</startdate><enddate>20171001</enddate><creator>Sun, Kyung Hoon</creator><creator>Karna, Sandeep</creator><creator>Moon, Young-Sook</creator><creator>Cho, Hoon</creator><creator>Choi, Cheol-Hee</creator><general>Springer Netherlands</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope></search><sort><creationdate>20171001</creationdate><title>The wound-healing effect of 7,3′,4′-trimethoxyflavone through increased levels of prostaglandin E2 by 15-hydroxyprostaglandin dehydrogenase inhibition</title><author>Sun, Kyung Hoon ; Karna, Sandeep ; Moon, Young-Sook ; Cho, Hoon ; Choi, Cheol-Hee</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c354t-f3a69c653a696e703f5ced3506346a63b93a1623a92649bfd165721e43124ac73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Applied Microbiology</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biotechnology</topic><topic>cytotoxicity</topic><topic>flavonoids</topic><topic>gene expression</topic><topic>Life Sciences</topic><topic>lung neoplasms</topic><topic>Microbiology</topic><topic>Original Research Paper</topic><topic>oxidoreductases</topic><topic>prostaglandins</topic><topic>therapeutics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sun, Kyung Hoon</creatorcontrib><creatorcontrib>Karna, Sandeep</creatorcontrib><creatorcontrib>Moon, Young-Sook</creatorcontrib><creatorcontrib>Cho, Hoon</creatorcontrib><creatorcontrib>Choi, Cheol-Hee</creatorcontrib><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Biotechnology letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sun, Kyung Hoon</au><au>Karna, Sandeep</au><au>Moon, Young-Sook</au><au>Cho, Hoon</au><au>Choi, Cheol-Hee</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The wound-healing effect of 7,3′,4′-trimethoxyflavone through increased levels of prostaglandin E2 by 15-hydroxyprostaglandin dehydrogenase inhibition</atitle><jtitle>Biotechnology letters</jtitle><stitle>Biotechnol Lett</stitle><date>2017-10-01</date><risdate>2017</risdate><volume>39</volume><issue>10</issue><spage>1575</spage><epage>1582</epage><pages>1575-1582</pages><issn>0141-5492</issn><eissn>1573-6776</eissn><abstract>Objective
To find an inhibitor of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) that rapidly metabolises Prostaglandin E
2
(PGE
2
) as a mediator of wound healing, we examined seven flavonoids for this role.
Results
7,3′,4′-Trimethoxyflavone (TMF) had the lowest IC
50
value of 0.34 µM for 15-PGDH inhibition but >400 µM for cytotoxicity, indicating a high therapeutic index. TMF elevated PGE
2
levels in a concentration-dependent manner in both A549 lung cancer and HaCaT cells. It also significantly increased mRNA expression of multidrug resistance-associated protein 4 (MRP4) and of prostaglandin transporter (PGT) slightly in HaCaT cells. In addition, TMF facilitated in vitro wound healing in a HaCaT scratch model, which was completely inhibited by adding both 15-PGDH and NAD
+
as cofactor, confirming the involvement of PGE
2
in its wound healing effect.
Conclusion
TMF with a high therapeutic index can facilitate wound healing through PGE
2
elevation by 15-PGDH inhibition.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><doi>10.1007/s10529-017-2386-2</doi><tpages>8</tpages></addata></record> |
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source | Springer Nature - Complete Springer Journals |
subjects | Applied Microbiology Biochemistry Biomedical and Life Sciences Biotechnology cytotoxicity flavonoids gene expression Life Sciences lung neoplasms Microbiology Original Research Paper oxidoreductases prostaglandins therapeutics |
title | The wound-healing effect of 7,3′,4′-trimethoxyflavone through increased levels of prostaglandin E2 by 15-hydroxyprostaglandin dehydrogenase inhibition |
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