Effect and Comparison of Luteolin and Its Derivative Sodium Luteolin-4′-sulfonate on Adipogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells through AMPK-Mediated PPARγ Signaling
Luteolin is a common phytochemical from the flavonoid family with a flavone structure. Studies reported several bioactivities for luteolin and similar flavones. Attenuating the increased adipogenesis of bone marrow cells (hBM-MSCs) has been regarded as a therapeutic target against osteoporotic bone...
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| creator | Jang, Mi-Soon Seo, Youngwan Lee, Jung Im Karadeniz, Fatih Oh, Jung Hwan Kong, Chang-Suk |
| description | Luteolin is a common phytochemical from the flavonoid family with a flavone structure. Studies reported several bioactivities for luteolin and similar flavones. Attenuating the increased adipogenesis of bone marrow cells (hBM-MSCs) has been regarded as a therapeutic target against osteoporotic bone disorders. In the present study, the potential roles of luteolin and its sulfonic acid derivative luteolin-OSO3Na in regulating adipogenic differentiation of hBM-MSCs were investigated. Adipo-induced cells were treated with or without compounds, and their effect on adipogenesis was evaluated by adipogenic marker levels such as lipid accumulation and PPARγ pathway activation. Luteolin hindered the adipogenic lipid accumulation in adipo-induced hBM-MSCs. Immunoblotting and reverse transcription-polymerase chain reaction analysis results indicated that luteolin downregulated PPARγ and downstream factors of C/EBPα and SREBP1c expression which resulted in inhibition of adipogenesis. Luteolin-OSO3Na showed similar effects; however, it was significantly less effective compared to luteolin. Investigating p38, JNK, and ERK MAPKs and AMPK activation indicated that luteolin suppressed the MAPK phosphorylation while stimulating AMPK phosphorylation. On the other hand, luteolin-OSO3Na was not able to notably affect the MAPK and AMPK activation. In conclusion, this study suggested that luteolin inhibited adipogenic differentiation of hBM-MSCs via upregulating AMPK activation. Replacing its 4′-hydroxyl group with sulfonic acid sodium salt diminished its antiadipogenic effect indicating its role in regulating AMPK activation. The general significance is that luteolin is a common phytochemical with various health-beneficial effects. The current study suggested that luteolin may serve as a lead compound for developing antiosteoporotic substances with antiadipogenic properties. |
| doi_str_mv | 10.1155/2020/8894910 |
| format | Article |
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Studies reported several bioactivities for luteolin and similar flavones. Attenuating the increased adipogenesis of bone marrow cells (hBM-MSCs) has been regarded as a therapeutic target against osteoporotic bone disorders. In the present study, the potential roles of luteolin and its sulfonic acid derivative luteolin-OSO3Na in regulating adipogenic differentiation of hBM-MSCs were investigated. Adipo-induced cells were treated with or without compounds, and their effect on adipogenesis was evaluated by adipogenic marker levels such as lipid accumulation and PPARγ pathway activation. Luteolin hindered the adipogenic lipid accumulation in adipo-induced hBM-MSCs. Immunoblotting and reverse transcription-polymerase chain reaction analysis results indicated that luteolin downregulated PPARγ and downstream factors of C/EBPα and SREBP1c expression which resulted in inhibition of adipogenesis. Luteolin-OSO3Na showed similar effects; however, it was significantly less effective compared to luteolin. Investigating p38, JNK, and ERK MAPKs and AMPK activation indicated that luteolin suppressed the MAPK phosphorylation while stimulating AMPK phosphorylation. On the other hand, luteolin-OSO3Na was not able to notably affect the MAPK and AMPK activation. In conclusion, this study suggested that luteolin inhibited adipogenic differentiation of hBM-MSCs via upregulating AMPK activation. Replacing its 4′-hydroxyl group with sulfonic acid sodium salt diminished its antiadipogenic effect indicating its role in regulating AMPK activation. The general significance is that luteolin is a common phytochemical with various health-beneficial effects. The current study suggested that luteolin may serve as a lead compound for developing antiosteoporotic substances with antiadipogenic properties.</description><identifier>ISSN: 1741-427X</identifier><identifier>EISSN: 1741-4288</identifier><identifier>DOI: 10.1155/2020/8894910</identifier><identifier>PMID: 33178328</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Publishing Corporation</publisher><subject>Adipocytes ; Adipogenesis ; Bone diseases ; Bone marrow ; Cancer ; Chemistry ; Diabetes ; Drug therapy ; Flavones ; Flavonoids ; Food ; Gene expression ; Immunoblotting ; Kinases ; MAP kinase ; Mesenchymal stem cells ; Obesity ; Osteoporosis ; Phosphorylation ; Polymerase chain reaction ; Reverse transcription ; Stem cells ; Sulfonic acid ; Thermogenesis</subject><ispartof>Evidence-based complementary and alternative medicine, 2020, Vol.2020 (2020), p.1-8</ispartof><rights>Copyright © 2020 Jung Hwan Oh et al.</rights><rights>Copyright © 2020 Jung Hwan Oh et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0</rights><rights>Copyright © 2020 Jung Hwan Oh et al. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c401t-aab77d25596f853c2e6de58b0cb10f7d7fe929e97cefb78fde07fa6d8fb5b6103</citedby><cites>FETCH-LOGICAL-c401t-aab77d25596f853c2e6de58b0cb10f7d7fe929e97cefb78fde07fa6d8fb5b6103</cites><orcidid>0000-0002-2304-9304</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644305/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644305/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,4024,27923,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33178328$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Yu, Zhilong</contributor><contributor>Zhilong Yu</contributor><creatorcontrib>Jang, Mi-Soon</creatorcontrib><creatorcontrib>Seo, Youngwan</creatorcontrib><creatorcontrib>Lee, Jung Im</creatorcontrib><creatorcontrib>Karadeniz, Fatih</creatorcontrib><creatorcontrib>Oh, Jung Hwan</creatorcontrib><creatorcontrib>Kong, Chang-Suk</creatorcontrib><title>Effect and Comparison of Luteolin and Its Derivative Sodium Luteolin-4′-sulfonate on Adipogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells through AMPK-Mediated PPARγ Signaling</title><title>Evidence-based complementary and alternative medicine</title><addtitle>Evid Based Complement Alternat Med</addtitle><description>Luteolin is a common phytochemical from the flavonoid family with a flavone structure. Studies reported several bioactivities for luteolin and similar flavones. Attenuating the increased adipogenesis of bone marrow cells (hBM-MSCs) has been regarded as a therapeutic target against osteoporotic bone disorders. In the present study, the potential roles of luteolin and its sulfonic acid derivative luteolin-OSO3Na in regulating adipogenic differentiation of hBM-MSCs were investigated. Adipo-induced cells were treated with or without compounds, and their effect on adipogenesis was evaluated by adipogenic marker levels such as lipid accumulation and PPARγ pathway activation. Luteolin hindered the adipogenic lipid accumulation in adipo-induced hBM-MSCs. Immunoblotting and reverse transcription-polymerase chain reaction analysis results indicated that luteolin downregulated PPARγ and downstream factors of C/EBPα and SREBP1c expression which resulted in inhibition of adipogenesis. Luteolin-OSO3Na showed similar effects; however, it was significantly less effective compared to luteolin. Investigating p38, JNK, and ERK MAPKs and AMPK activation indicated that luteolin suppressed the MAPK phosphorylation while stimulating AMPK phosphorylation. On the other hand, luteolin-OSO3Na was not able to notably affect the MAPK and AMPK activation. In conclusion, this study suggested that luteolin inhibited adipogenic differentiation of hBM-MSCs via upregulating AMPK activation. Replacing its 4′-hydroxyl group with sulfonic acid sodium salt diminished its antiadipogenic effect indicating its role in regulating AMPK activation. The general significance is that luteolin is a common phytochemical with various health-beneficial effects. The current study suggested that luteolin may serve as a lead compound for developing antiosteoporotic substances with antiadipogenic properties.</description><subject>Adipocytes</subject><subject>Adipogenesis</subject><subject>Bone diseases</subject><subject>Bone marrow</subject><subject>Cancer</subject><subject>Chemistry</subject><subject>Diabetes</subject><subject>Drug therapy</subject><subject>Flavones</subject><subject>Flavonoids</subject><subject>Food</subject><subject>Gene expression</subject><subject>Immunoblotting</subject><subject>Kinases</subject><subject>MAP kinase</subject><subject>Mesenchymal stem cells</subject><subject>Obesity</subject><subject>Osteoporosis</subject><subject>Phosphorylation</subject><subject>Polymerase chain reaction</subject><subject>Reverse transcription</subject><subject>Stem cells</subject><subject>Sulfonic acid</subject><subject>Thermogenesis</subject><issn>1741-427X</issn><issn>1741-4288</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNksuO0zAUhiMEYi6wY40ssUEawtjOxc4GqXQGZkQrKgoSu8iJjxOPErvYSUez45ngNRAPwZPgTku5rFjZkj9_5_zSH0WPCH5OSJadUkzxKedFWhB8JzokLCVxSjm_u7-zjwfRkfdXGNOCMXY_OkgSwnhC-WH07VwpqAckjERT26-E094aZBWajQPYTpvbp8vBozNwei0GvQa0tFKP_R6J0x-fv8R-7JQ1YgAUBBOpV7YBo2t0psMIB2bQ4fPWfTH2wqCX1gCaC-fsdXwrB4nm4MHU7U0vOrQcoEdT6DqPhtbZsWnRZL54E89BBlWAF4vJu-9f0VI3RoQ1mgfRPSU6Dw9353H04dX5--lFPHv7-nI6mcV1iskQC1ExJmmWFbniWVJTyCVkvMJ1RbBikikoaAEFq0FVjCsJmCmRS66qrMoJTo6jF1vvaqx6kHXI5kRXrpzuhbsprdDl3y9Gt2Vj1yXL0zTBWRA83Qmc_TSCH8pe-zokFQbs6Eua5hhzwvFm1pN_0Cs7upB3Q2U85ZQVJFDPtlTtrPcO1H4ZgstNTcpNTcpdTQL--M8Ae_hXLwJwsgVabaS41v-pg8CAEr9pknFKcfITRurVHQ</recordid><startdate>2020</startdate><enddate>2020</enddate><creator>Jang, Mi-Soon</creator><creator>Seo, Youngwan</creator><creator>Lee, Jung Im</creator><creator>Karadeniz, Fatih</creator><creator>Oh, Jung Hwan</creator><creator>Kong, Chang-Suk</creator><general>Hindawi Publishing Corporation</general><general>Hindawi</general><general>Hindawi Limited</general><scope>ADJCN</scope><scope>AHFXO</scope><scope>RHU</scope><scope>RHW</scope><scope>RHX</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7T5</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88G</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M2M</scope><scope>M2O</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-2304-9304</orcidid></search><sort><creationdate>2020</creationdate><title>Effect and Comparison of Luteolin and Its Derivative Sodium Luteolin-4′-sulfonate on Adipogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells through AMPK-Mediated PPARγ Signaling</title><author>Jang, Mi-Soon ; Seo, Youngwan ; Lee, Jung Im ; Karadeniz, Fatih ; Oh, Jung Hwan ; Kong, Chang-Suk</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c401t-aab77d25596f853c2e6de58b0cb10f7d7fe929e97cefb78fde07fa6d8fb5b6103</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adipocytes</topic><topic>Adipogenesis</topic><topic>Bone diseases</topic><topic>Bone marrow</topic><topic>Cancer</topic><topic>Chemistry</topic><topic>Diabetes</topic><topic>Drug therapy</topic><topic>Flavones</topic><topic>Flavonoids</topic><topic>Food</topic><topic>Gene expression</topic><topic>Immunoblotting</topic><topic>Kinases</topic><topic>MAP kinase</topic><topic>Mesenchymal stem cells</topic><topic>Obesity</topic><topic>Osteoporosis</topic><topic>Phosphorylation</topic><topic>Polymerase chain reaction</topic><topic>Reverse transcription</topic><topic>Stem cells</topic><topic>Sulfonic acid</topic><topic>Thermogenesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jang, Mi-Soon</creatorcontrib><creatorcontrib>Seo, Youngwan</creatorcontrib><creatorcontrib>Lee, Jung Im</creatorcontrib><creatorcontrib>Karadeniz, Fatih</creatorcontrib><creatorcontrib>Oh, Jung Hwan</creatorcontrib><creatorcontrib>Kong, Chang-Suk</creatorcontrib><collection>الدوريات العلمية والإحصائية - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Evidence-based complementary and alternative medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jang, Mi-Soon</au><au>Seo, Youngwan</au><au>Lee, Jung Im</au><au>Karadeniz, Fatih</au><au>Oh, Jung Hwan</au><au>Kong, Chang-Suk</au><au>Yu, Zhilong</au><au>Zhilong Yu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect and Comparison of Luteolin and Its Derivative Sodium Luteolin-4′-sulfonate on Adipogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells through AMPK-Mediated PPARγ Signaling</atitle><jtitle>Evidence-based complementary and alternative medicine</jtitle><addtitle>Evid Based Complement Alternat Med</addtitle><date>2020</date><risdate>2020</risdate><volume>2020</volume><issue>2020</issue><spage>1</spage><epage>8</epage><pages>1-8</pages><issn>1741-427X</issn><eissn>1741-4288</eissn><abstract>Luteolin is a common phytochemical from the flavonoid family with a flavone structure. Studies reported several bioactivities for luteolin and similar flavones. Attenuating the increased adipogenesis of bone marrow cells (hBM-MSCs) has been regarded as a therapeutic target against osteoporotic bone disorders. In the present study, the potential roles of luteolin and its sulfonic acid derivative luteolin-OSO3Na in regulating adipogenic differentiation of hBM-MSCs were investigated. Adipo-induced cells were treated with or without compounds, and their effect on adipogenesis was evaluated by adipogenic marker levels such as lipid accumulation and PPARγ pathway activation. Luteolin hindered the adipogenic lipid accumulation in adipo-induced hBM-MSCs. Immunoblotting and reverse transcription-polymerase chain reaction analysis results indicated that luteolin downregulated PPARγ and downstream factors of C/EBPα and SREBP1c expression which resulted in inhibition of adipogenesis. Luteolin-OSO3Na showed similar effects; however, it was significantly less effective compared to luteolin. Investigating p38, JNK, and ERK MAPKs and AMPK activation indicated that luteolin suppressed the MAPK phosphorylation while stimulating AMPK phosphorylation. On the other hand, luteolin-OSO3Na was not able to notably affect the MAPK and AMPK activation. In conclusion, this study suggested that luteolin inhibited adipogenic differentiation of hBM-MSCs via upregulating AMPK activation. Replacing its 4′-hydroxyl group with sulfonic acid sodium salt diminished its antiadipogenic effect indicating its role in regulating AMPK activation. The general significance is that luteolin is a common phytochemical with various health-beneficial effects. The current study suggested that luteolin may serve as a lead compound for developing antiosteoporotic substances with antiadipogenic properties.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Publishing Corporation</pub><pmid>33178328</pmid><doi>10.1155/2020/8894910</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-2304-9304</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Evidence-based complementary and alternative medicine, 2020, Vol.2020 (2020), p.1-8 |
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| source | PubMed Central (Open Access); Wiley Online Library Open Access; Alma/SFX Local Collection; EZB Electronic Journals Library; PubMed Central Open Access |
| subjects | Adipocytes Adipogenesis Bone diseases Bone marrow Cancer Chemistry Diabetes Drug therapy Flavones Flavonoids Food Gene expression Immunoblotting Kinases MAP kinase Mesenchymal stem cells Obesity Osteoporosis Phosphorylation Polymerase chain reaction Reverse transcription Stem cells Sulfonic acid Thermogenesis |
| title | Effect and Comparison of Luteolin and Its Derivative Sodium Luteolin-4′-sulfonate on Adipogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells through AMPK-Mediated PPARγ Signaling |
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