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Combined cereal and pulse flavonoids show enhanced bioavailability by downregulating phase II metabolism and ABC membrane transporter function in Caco-2 model
•Cereals and pulses are complementary dietary commodities.•Cereals and pulse flavonoids are structurally different.•Combined cereal flavones and pulse flavonols show enhanced absorption.•Effect due to suppression of phase II metabolism and ABC transporter function.•Strategic combinations of cereal a...
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| Published in: | Food chemistry 2019-05, Vol.279, p.88-97 |
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| Main Authors: | , , , , , |
| Format: | Article |
| Language: | English |
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| cites | cdi_FETCH-LOGICAL-c486t-50cf8e6dc09b9f17943bbf79af0365d974830de45e0d3e9771474b35892e5a5f3 |
| container_end_page | 97 |
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| container_start_page | 88 |
| container_title | Food chemistry |
| container_volume | 279 |
| creator | Ravisankar, Shreeya Agah, Shima Kim, Hyemee Talcott, Susanne Wu, Chaodong Awika, Joseph |
| description | •Cereals and pulses are complementary dietary commodities.•Cereals and pulse flavonoids are structurally different.•Combined cereal flavones and pulse flavonols show enhanced absorption.•Effect due to suppression of phase II metabolism and ABC transporter function.•Strategic combinations of cereal and pulses could enhance biological benefits.
Predominant flavonoids in cereals and pulses are structurally different and may positively interact to enhance bioactivity in combined diet. This work investigated the effects of combined cereal 3-deoxyflavonoids (apigenin, naringenin) and pulse flavonols (quercetin), along with natural extracts, on their bioavailability and underlying mechanisms using Caco-2 monolayer model. Membrane permeability, phase II metabolism, and ATP binding cassette (ABC) membrane transporter expression and function were measured. Apparent absorption of quercetin and apigenin increased (p |
| doi_str_mv | 10.1016/j.foodchem.2018.12.006 |
| format | article |
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Predominant flavonoids in cereals and pulses are structurally different and may positively interact to enhance bioactivity in combined diet. This work investigated the effects of combined cereal 3-deoxyflavonoids (apigenin, naringenin) and pulse flavonols (quercetin), along with natural extracts, on their bioavailability and underlying mechanisms using Caco-2 monolayer model. Membrane permeability, phase II metabolism, and ATP binding cassette (ABC) membrane transporter expression and function were measured. Apparent absorption of quercetin and apigenin increased (p < 0.05) 3.3× and 1.5×, respectively, while both compounds were significantly less metabolized in combined treatments. Combinations with naringenin had insignificant effect, suggesting a role for flavonoid C2C3 conjugation. Both natural extracts and apigenin-quercetin combinations synergistically (3–40 fold) downregulated ABC transporter expression, and inhibited P-glycoprotein activity, suggesting direct binding and inhibition of ATPase. Combination of conjugated cereal and pulse flavonoids enhances their potential bioavailability through synergistic inhibition of membrane transporter and phase II enzyme function.</description><identifier>ISSN: 0308-8146</identifier><identifier>EISSN: 1873-7072</identifier><identifier>DOI: 10.1016/j.foodchem.2018.12.006</identifier><identifier>PMID: 30611516</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>ABC transporter ; adenosine triphosphate ; adenosinetriphosphatase ; apigenin ; Apigenin - metabolism ; Apigenin - pharmacology ; ATP-Binding Cassette Transporters - genetics ; ATP-Binding Cassette Transporters - metabolism ; bioactive properties ; bioavailability ; Biological Availability ; Caco-2 Cells ; Cell Membrane Permeability - drug effects ; Cereal grain ; diet ; Down-Regulation - drug effects ; Edible Grain - metabolism ; enzyme inhibition ; Flavanones - metabolism ; Flavanones - pharmacology ; Flavonoid ; Flavonoids - metabolism ; Flavonoids - pharmacology ; Grain pulses ; grains ; Humans ; membrane permeability ; metabolism ; naringenin ; P-glycoproteins ; Phase II metabolism ; Polyphenol bioavailability ; quercetin ; Quercetin - metabolism ; Quercetin - pharmacology ; Synergistic interaction</subject><ispartof>Food chemistry, 2019-05, Vol.279, p.88-97</ispartof><rights>2018 Elsevier Ltd</rights><rights>Copyright © 2018 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c486t-50cf8e6dc09b9f17943bbf79af0365d974830de45e0d3e9771474b35892e5a5f3</citedby><cites>FETCH-LOGICAL-c486t-50cf8e6dc09b9f17943bbf79af0365d974830de45e0d3e9771474b35892e5a5f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30611516$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ravisankar, Shreeya</creatorcontrib><creatorcontrib>Agah, Shima</creatorcontrib><creatorcontrib>Kim, Hyemee</creatorcontrib><creatorcontrib>Talcott, Susanne</creatorcontrib><creatorcontrib>Wu, Chaodong</creatorcontrib><creatorcontrib>Awika, Joseph</creatorcontrib><title>Combined cereal and pulse flavonoids show enhanced bioavailability by downregulating phase II metabolism and ABC membrane transporter function in Caco-2 model</title><title>Food chemistry</title><addtitle>Food Chem</addtitle><description>•Cereals and pulses are complementary dietary commodities.•Cereals and pulse flavonoids are structurally different.•Combined cereal flavones and pulse flavonols show enhanced absorption.•Effect due to suppression of phase II metabolism and ABC transporter function.•Strategic combinations of cereal and pulses could enhance biological benefits.
Predominant flavonoids in cereals and pulses are structurally different and may positively interact to enhance bioactivity in combined diet. This work investigated the effects of combined cereal 3-deoxyflavonoids (apigenin, naringenin) and pulse flavonols (quercetin), along with natural extracts, on their bioavailability and underlying mechanisms using Caco-2 monolayer model. Membrane permeability, phase II metabolism, and ATP binding cassette (ABC) membrane transporter expression and function were measured. Apparent absorption of quercetin and apigenin increased (p < 0.05) 3.3× and 1.5×, respectively, while both compounds were significantly less metabolized in combined treatments. Combinations with naringenin had insignificant effect, suggesting a role for flavonoid C2C3 conjugation. Both natural extracts and apigenin-quercetin combinations synergistically (3–40 fold) downregulated ABC transporter expression, and inhibited P-glycoprotein activity, suggesting direct binding and inhibition of ATPase. Combination of conjugated cereal and pulse flavonoids enhances their potential bioavailability through synergistic inhibition of membrane transporter and phase II enzyme function.</description><subject>ABC transporter</subject><subject>adenosine triphosphate</subject><subject>adenosinetriphosphatase</subject><subject>apigenin</subject><subject>Apigenin - metabolism</subject><subject>Apigenin - pharmacology</subject><subject>ATP-Binding Cassette Transporters - genetics</subject><subject>ATP-Binding Cassette Transporters - metabolism</subject><subject>bioactive properties</subject><subject>bioavailability</subject><subject>Biological Availability</subject><subject>Caco-2 Cells</subject><subject>Cell Membrane Permeability - drug effects</subject><subject>Cereal grain</subject><subject>diet</subject><subject>Down-Regulation - drug effects</subject><subject>Edible Grain - metabolism</subject><subject>enzyme inhibition</subject><subject>Flavanones - metabolism</subject><subject>Flavanones - pharmacology</subject><subject>Flavonoid</subject><subject>Flavonoids - metabolism</subject><subject>Flavonoids - pharmacology</subject><subject>Grain pulses</subject><subject>grains</subject><subject>Humans</subject><subject>membrane permeability</subject><subject>metabolism</subject><subject>naringenin</subject><subject>P-glycoproteins</subject><subject>Phase II metabolism</subject><subject>Polyphenol bioavailability</subject><subject>quercetin</subject><subject>Quercetin - metabolism</subject><subject>Quercetin - pharmacology</subject><subject>Synergistic interaction</subject><issn>0308-8146</issn><issn>1873-7072</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNqFkcluFDEQhi0EIpPAK0Q-cumOl15vhBbLSJG4wNnyUs545LYHu3uieRmeFQ-TcOVSJZW--mv5EbqlpKaEdnf72sZo9A7mmhE61JTVhHSv0IYOPa960rPXaEM4GaqBNt0Vus55Twg5s2_RFScdpS3tNuj3FGflAhisIYH0WAaDD6vPgK2XxxiiMxnnXXzCEHYy6EIqF-VROi-V8245YXXCJj6FBI-rl4sLj_iwk0Vgu8UzLFJF7_L8V_j-01RKs0oyAF5KzIeYFkjYrkEvLgbsAp6kjhXDczTg36E3VpZl3j_nG_Tzy-cf07fq4fvX7XT_UOlm6JaqJdoO0BlNRjVa2o8NV8r2o7SEd60Z-2bgxEDTAjEcxr6nTd8o3g4jg1a2lt-gDxfdQ4q_VsiLmF3W4H1ZNK5ZMMYoYZwNpKDdBdUp5pzAikNys0wnQYk4eyP24sUbcf63oEwUb0rj7fOMVc1g_rW9mFGAjxcAyqVHB0lk7eD8cpdAL8JE978ZfwCYMKYA</recordid><startdate>20190501</startdate><enddate>20190501</enddate><creator>Ravisankar, Shreeya</creator><creator>Agah, Shima</creator><creator>Kim, Hyemee</creator><creator>Talcott, Susanne</creator><creator>Wu, Chaodong</creator><creator>Awika, Joseph</creator><general>Elsevier Ltd</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>7S9</scope><scope>L.6</scope></search><sort><creationdate>20190501</creationdate><title>Combined cereal and pulse flavonoids show enhanced bioavailability by downregulating phase II metabolism and ABC membrane transporter function in Caco-2 model</title><author>Ravisankar, Shreeya ; Agah, Shima ; Kim, Hyemee ; Talcott, Susanne ; Wu, Chaodong ; Awika, Joseph</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c486t-50cf8e6dc09b9f17943bbf79af0365d974830de45e0d3e9771474b35892e5a5f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>ABC transporter</topic><topic>adenosine triphosphate</topic><topic>adenosinetriphosphatase</topic><topic>apigenin</topic><topic>Apigenin - metabolism</topic><topic>Apigenin - pharmacology</topic><topic>ATP-Binding Cassette Transporters - genetics</topic><topic>ATP-Binding Cassette Transporters - metabolism</topic><topic>bioactive properties</topic><topic>bioavailability</topic><topic>Biological Availability</topic><topic>Caco-2 Cells</topic><topic>Cell Membrane Permeability - drug effects</topic><topic>Cereal grain</topic><topic>diet</topic><topic>Down-Regulation - drug effects</topic><topic>Edible Grain - metabolism</topic><topic>enzyme inhibition</topic><topic>Flavanones - metabolism</topic><topic>Flavanones - pharmacology</topic><topic>Flavonoid</topic><topic>Flavonoids - metabolism</topic><topic>Flavonoids - pharmacology</topic><topic>Grain pulses</topic><topic>grains</topic><topic>Humans</topic><topic>membrane permeability</topic><topic>metabolism</topic><topic>naringenin</topic><topic>P-glycoproteins</topic><topic>Phase II metabolism</topic><topic>Polyphenol bioavailability</topic><topic>quercetin</topic><topic>Quercetin - metabolism</topic><topic>Quercetin - pharmacology</topic><topic>Synergistic interaction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ravisankar, Shreeya</creatorcontrib><creatorcontrib>Agah, Shima</creatorcontrib><creatorcontrib>Kim, Hyemee</creatorcontrib><creatorcontrib>Talcott, Susanne</creatorcontrib><creatorcontrib>Wu, Chaodong</creatorcontrib><creatorcontrib>Awika, Joseph</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Food chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ravisankar, Shreeya</au><au>Agah, Shima</au><au>Kim, Hyemee</au><au>Talcott, Susanne</au><au>Wu, Chaodong</au><au>Awika, Joseph</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Combined cereal and pulse flavonoids show enhanced bioavailability by downregulating phase II metabolism and ABC membrane transporter function in Caco-2 model</atitle><jtitle>Food chemistry</jtitle><addtitle>Food Chem</addtitle><date>2019-05-01</date><risdate>2019</risdate><volume>279</volume><spage>88</spage><epage>97</epage><pages>88-97</pages><issn>0308-8146</issn><eissn>1873-7072</eissn><abstract>•Cereals and pulses are complementary dietary commodities.•Cereals and pulse flavonoids are structurally different.•Combined cereal flavones and pulse flavonols show enhanced absorption.•Effect due to suppression of phase II metabolism and ABC transporter function.•Strategic combinations of cereal and pulses could enhance biological benefits.
Predominant flavonoids in cereals and pulses are structurally different and may positively interact to enhance bioactivity in combined diet. This work investigated the effects of combined cereal 3-deoxyflavonoids (apigenin, naringenin) and pulse flavonols (quercetin), along with natural extracts, on their bioavailability and underlying mechanisms using Caco-2 monolayer model. Membrane permeability, phase II metabolism, and ATP binding cassette (ABC) membrane transporter expression and function were measured. Apparent absorption of quercetin and apigenin increased (p < 0.05) 3.3× and 1.5×, respectively, while both compounds were significantly less metabolized in combined treatments. Combinations with naringenin had insignificant effect, suggesting a role for flavonoid C2C3 conjugation. Both natural extracts and apigenin-quercetin combinations synergistically (3–40 fold) downregulated ABC transporter expression, and inhibited P-glycoprotein activity, suggesting direct binding and inhibition of ATPase. Combination of conjugated cereal and pulse flavonoids enhances their potential bioavailability through synergistic inhibition of membrane transporter and phase II enzyme function.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>30611516</pmid><doi>10.1016/j.foodchem.2018.12.006</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Food chemistry, 2019-05, Vol.279, p.88-97 |
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| source | ScienceDirect Freedom Collection |
| subjects | ABC transporter adenosine triphosphate adenosinetriphosphatase apigenin Apigenin - metabolism Apigenin - pharmacology ATP-Binding Cassette Transporters - genetics ATP-Binding Cassette Transporters - metabolism bioactive properties bioavailability Biological Availability Caco-2 Cells Cell Membrane Permeability - drug effects Cereal grain diet Down-Regulation - drug effects Edible Grain - metabolism enzyme inhibition Flavanones - metabolism Flavanones - pharmacology Flavonoid Flavonoids - metabolism Flavonoids - pharmacology Grain pulses grains Humans membrane permeability metabolism naringenin P-glycoproteins Phase II metabolism Polyphenol bioavailability quercetin Quercetin - metabolism Quercetin - pharmacology Synergistic interaction |
| title | Combined cereal and pulse flavonoids show enhanced bioavailability by downregulating phase II metabolism and ABC membrane transporter function in Caco-2 model |
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