Investigation of Herb-Drug Interactions between Xylopia aethiopica, Its Principal Constituent Xylopic Acid, and Antidepressants

Introduction. Depression affects an estimated 350 million people worldwide and is implicated in up to 60% of suicides. Only about 60–70% of patients respond to antidepressant therapy. One of the factors causing patients to not attain therapeutic goals is herb-drug interactions. Objective. To investi...

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Published in:Advances in pharmacological and pharmaceutical sciences 2024-05, Vol.2024, p.9923801-16
Main Authors: Ndu, Christian C., Abotsi, Wonder K. M., Mante, Priscilla K.
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Language:English
Subjects:
Acids
Analysis
Antidepressants
Complications and side effects
Dried fruit
Drug dosages
Drug interactions
Ethics
Fluoxetine
Imipramine
Investigations
Laboratory animals
Medical research
Pharmacodynamics
Pharmacokinetics
Serotonin
Suicides & suicide attempts
Toxicity
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description Introduction. Depression affects an estimated 350 million people worldwide and is implicated in up to 60% of suicides. Only about 60–70% of patients respond to antidepressant therapy. One of the factors causing patients to not attain therapeutic goals is herb-drug interactions. Objective. To investigate any potential herb-drug interaction that might exist between Xylopia aethiopica extract (XAE) or xylopic acid (XA) and selected conventional antidepressants (imipramine, fluoxetine, and venlafaxine) in mice. Methods. Dried, powdered fruits of Xylopia aethiopica were cold macerated in 70% ethanol to obtain XAE. XA was isolated by cold macerating dried fruits of Xylopia aethiopica in petroleum ether, crystallising impure XA with ethyl acetate, and purifying XA crystals with 96% ethanol. Pharmacodynamic interaction was assessed via isobolographic analysis of tail suspension tests of the agents individually and in their respective combinations. Pharmacokinetic interaction was assessed by monitoring the effect of coadministrations on the plasma concentration of antidepressants and xylopic acid via HPLC analysis. Results. XAE and XA in mice showed significant antidepressant-like activity in the tail suspension test. With interaction indices less than one, synergism of antidepressant effect was observed in the Xylopia aethiopica extract/fluoxetine (γXAE/FL = 0.502), Xylopia aethiopica extract/imipramine (γXAE/IP = 0.322), Xylopia aethiopica extract/venlafaxine (γXAE/VL = 0.601), xylopic acid/imipramine (γXA/IP = 0.556), xylopic acid/venlafaxine (γXA/VL = 0.451), and xylopic acid/fluoxetine (γXA/FL = 0.298) combinations, which may be potentially due to elevation of serotonergic neurotransmission via varying mechanisms. The AUC of imipramine (AUCIP = 1966 ± 58.98 µg/ml.h) was significantly (P
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M. ; Mante, Priscilla K.</creator><contributor>Natalini, Benedetto ; Benedetto Natalini</contributor><creatorcontrib>Ndu, Christian C. ; Abotsi, Wonder K. M. ; Mante, Priscilla K. ; Natalini, Benedetto ; Benedetto Natalini</creatorcontrib><description>Introduction. Depression affects an estimated 350 million people worldwide and is implicated in up to 60% of suicides. Only about 60–70% of patients respond to antidepressant therapy. One of the factors causing patients to not attain therapeutic goals is herb-drug interactions. Objective. To investigate any potential herb-drug interaction that might exist between Xylopia aethiopica extract (XAE) or xylopic acid (XA) and selected conventional antidepressants (imipramine, fluoxetine, and venlafaxine) in mice. Methods. Dried, powdered fruits of Xylopia aethiopica were cold macerated in 70% ethanol to obtain XAE. XA was isolated by cold macerating dried fruits of Xylopia aethiopica in petroleum ether, crystallising impure XA with ethyl acetate, and purifying XA crystals with 96% ethanol. Pharmacodynamic interaction was assessed via isobolographic analysis of tail suspension tests of the agents individually and in their respective combinations. Pharmacokinetic interaction was assessed by monitoring the effect of coadministrations on the plasma concentration of antidepressants and xylopic acid via HPLC analysis. Results. XAE and XA in mice showed significant antidepressant-like activity in the tail suspension test. With interaction indices less than one, synergism of antidepressant effect was observed in the Xylopia aethiopica extract/fluoxetine (γXAE/FL = 0.502), Xylopia aethiopica extract/imipramine (γXAE/IP = 0.322), Xylopia aethiopica extract/venlafaxine (γXAE/VL = 0.601), xylopic acid/imipramine (γXA/IP = 0.556), xylopic acid/venlafaxine (γXA/VL = 0.451), and xylopic acid/fluoxetine (γXA/FL = 0.298) combinations, which may be potentially due to elevation of serotonergic neurotransmission via varying mechanisms. The AUC of imipramine (AUCIP = 1966 ± 58.98 µg/ml.h) was significantly (P&lt;0.0001) reduced by Xylopia aethiopica extract (AUCIP = 1228 ± 67.40 µg/ml.h) and xylopic acid (AUCIP = 1250 ± 55.95 µg/ml.h), while the AUC of xylopic acid (AUCXA = 968.10 ± 61.22 µg/ml.h) was significantly (P&lt;0.0001) reduced by venlafaxine (AUCXA = 285.90 ± 51.92 µg/ml.h) and fluoxetine (AUCXA = 510.60 ± 44.74 µg/ml.h), possibly due to the effect of interfering agents on gastric emptying hence reducing oral absorption. Conclusion. Xylopia aethiopica extract and xylopic acid interacted synergistically with imipramine, fluoxetine, and venlafaxine and reduced the systemic circulation of imipramine.</description><identifier>ISSN: 2633-4682</identifier><identifier>ISSN: 2633-4690</identifier><identifier>EISSN: 2633-4690</identifier><identifier>DOI: 10.1155/2024/9923801</identifier><identifier>PMID: 38826835</identifier><language>eng</language><publisher>England: Wiley</publisher><subject>Acids ; Analysis ; Antidepressants ; Complications and side effects ; Dried fruit ; Drug dosages ; Drug interactions ; Ethics ; Fluoxetine ; Imipramine ; Investigations ; Laboratory animals ; Medical research ; Pharmacodynamics ; Pharmacokinetics ; Serotonin ; Suicides &amp; suicide attempts ; Toxicity</subject><ispartof>Advances in pharmacological and pharmaceutical sciences, 2024-05, Vol.2024, p.9923801-16</ispartof><rights>Copyright © 2024 Christian C. Ndu et al.</rights><rights>COPYRIGHT 2024 John Wiley &amp; Sons, Inc.</rights><rights>Copyright © 2024 Christian C. Ndu 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><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c447t-2b795b885da10f1b8d1172412a00552f10fe2cdf3adbc27e06caa4e2a64ff6723</cites><orcidid>0000-0002-0021-4231 ; 0009-0007-7748-679X ; 0000-0002-6886-7570</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/3063153937/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/3063153937?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,25751,27922,27923,37010,37011,38514,43893,44588,74182,74896</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38826835$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Natalini, Benedetto</contributor><contributor>Benedetto Natalini</contributor><creatorcontrib>Ndu, Christian C.</creatorcontrib><creatorcontrib>Abotsi, Wonder K. M.</creatorcontrib><creatorcontrib>Mante, Priscilla K.</creatorcontrib><title>Investigation of Herb-Drug Interactions between Xylopia aethiopica, Its Principal Constituent Xylopic Acid, and Antidepressants</title><title>Advances in pharmacological and pharmaceutical sciences</title><addtitle>Adv Pharmacol Pharm Sci</addtitle><description>Introduction. Depression affects an estimated 350 million people worldwide and is implicated in up to 60% of suicides. Only about 60–70% of patients respond to antidepressant therapy. One of the factors causing patients to not attain therapeutic goals is herb-drug interactions. Objective. To investigate any potential herb-drug interaction that might exist between Xylopia aethiopica extract (XAE) or xylopic acid (XA) and selected conventional antidepressants (imipramine, fluoxetine, and venlafaxine) in mice. Methods. Dried, powdered fruits of Xylopia aethiopica were cold macerated in 70% ethanol to obtain XAE. XA was isolated by cold macerating dried fruits of Xylopia aethiopica in petroleum ether, crystallising impure XA with ethyl acetate, and purifying XA crystals with 96% ethanol. Pharmacodynamic interaction was assessed via isobolographic analysis of tail suspension tests of the agents individually and in their respective combinations. Pharmacokinetic interaction was assessed by monitoring the effect of coadministrations on the plasma concentration of antidepressants and xylopic acid via HPLC analysis. Results. XAE and XA in mice showed significant antidepressant-like activity in the tail suspension test. With interaction indices less than one, synergism of antidepressant effect was observed in the Xylopia aethiopica extract/fluoxetine (γXAE/FL = 0.502), Xylopia aethiopica extract/imipramine (γXAE/IP = 0.322), Xylopia aethiopica extract/venlafaxine (γXAE/VL = 0.601), xylopic acid/imipramine (γXA/IP = 0.556), xylopic acid/venlafaxine (γXA/VL = 0.451), and xylopic acid/fluoxetine (γXA/FL = 0.298) combinations, which may be potentially due to elevation of serotonergic neurotransmission via varying mechanisms. The AUC of imipramine (AUCIP = 1966 ± 58.98 µg/ml.h) was significantly (P&lt;0.0001) reduced by Xylopia aethiopica extract (AUCIP = 1228 ± 67.40 µg/ml.h) and xylopic acid (AUCIP = 1250 ± 55.95 µg/ml.h), while the AUC of xylopic acid (AUCXA = 968.10 ± 61.22 µg/ml.h) was significantly (P&lt;0.0001) reduced by venlafaxine (AUCXA = 285.90 ± 51.92 µg/ml.h) and fluoxetine (AUCXA = 510.60 ± 44.74 µg/ml.h), possibly due to the effect of interfering agents on gastric emptying hence reducing oral absorption. Conclusion. Xylopia aethiopica extract and xylopic acid interacted synergistically with imipramine, fluoxetine, and venlafaxine and reduced the systemic circulation of imipramine.</description><subject>Acids</subject><subject>Analysis</subject><subject>Antidepressants</subject><subject>Complications and side effects</subject><subject>Dried fruit</subject><subject>Drug dosages</subject><subject>Drug interactions</subject><subject>Ethics</subject><subject>Fluoxetine</subject><subject>Imipramine</subject><subject>Investigations</subject><subject>Laboratory animals</subject><subject>Medical research</subject><subject>Pharmacodynamics</subject><subject>Pharmacokinetics</subject><subject>Serotonin</subject><subject>Suicides &amp; suicide attempts</subject><subject>Toxicity</subject><issn>2633-4682</issn><issn>2633-4690</issn><issn>2633-4690</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>COVID</sourceid><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNp9ksuLUzEUxi-iOMM4O9cScKPYzuR1X8tSH1MYUHyAu3Bucm4n5TbpJLmOs_JfN7W1UhHJIocvv_OFc_iK4imjF4yV5SWnXF62LRcNZQ-KU14JMZVVSx8e6oafFOcxriilnLcVE9Xj4kQ0Da8aUZ4WPxbuG8Zkl5Csd8T35ApDN30dxiVZuIQB9PYhkg7THaIjX-8Hv7FAANONzZWGCVmkSD4E67TdwEDmGU82jejSntZkpq2ZEHCGzFyyBjcBYwSX4pPiUQ9DxPP9fVZ8efvm8_xqev3-3WI-u55qKes05V3dll3TlAYY7VnXGMZqLhkHSsuS91lErk0vwHSa10grDSCRQyX7vqq5OCsWO1_jYaU2wa4h3CsPVv0SfFgqCMnqAZXmUgA1Le81SilFJ-sGa2TGMNNrg9nrxc5rE_ztmLen1jZqHAZw6MeoBK0kE21Vtxl9_he68mNwedItJVgpWlH_oZaQ_7eu9ynvfWuqZnVb0ZqXtMnUxT-ofAyurfYOe5v1o4aXRw2ZSfg9LWGMUS0-fTxmJztWBx9jwP6wI0bVNmpqGzW1j1rGn-3nGrs1mgP8O1gZeLUDbqwzcGf_b_cTmFXZcA</recordid><startdate>20240525</startdate><enddate>20240525</enddate><creator>Ndu, Christian C.</creator><creator>Abotsi, Wonder K. 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M. ; Mante, Priscilla K.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c447t-2b795b885da10f1b8d1172412a00552f10fe2cdf3adbc27e06caa4e2a64ff6723</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Acids</topic><topic>Analysis</topic><topic>Antidepressants</topic><topic>Complications and side effects</topic><topic>Dried fruit</topic><topic>Drug dosages</topic><topic>Drug interactions</topic><topic>Ethics</topic><topic>Fluoxetine</topic><topic>Imipramine</topic><topic>Investigations</topic><topic>Laboratory animals</topic><topic>Medical research</topic><topic>Pharmacodynamics</topic><topic>Pharmacokinetics</topic><topic>Serotonin</topic><topic>Suicides &amp; suicide attempts</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ndu, Christian C.</creatorcontrib><creatorcontrib>Abotsi, Wonder K. 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M.</au><au>Mante, Priscilla K.</au><au>Natalini, Benedetto</au><au>Benedetto Natalini</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Investigation of Herb-Drug Interactions between Xylopia aethiopica, Its Principal Constituent Xylopic Acid, and Antidepressants</atitle><jtitle>Advances in pharmacological and pharmaceutical sciences</jtitle><addtitle>Adv Pharmacol Pharm Sci</addtitle><date>2024-05-25</date><risdate>2024</risdate><volume>2024</volume><spage>9923801</spage><epage>16</epage><pages>9923801-16</pages><issn>2633-4682</issn><issn>2633-4690</issn><eissn>2633-4690</eissn><abstract>Introduction. Depression affects an estimated 350 million people worldwide and is implicated in up to 60% of suicides. Only about 60–70% of patients respond to antidepressant therapy. One of the factors causing patients to not attain therapeutic goals is herb-drug interactions. Objective. To investigate any potential herb-drug interaction that might exist between Xylopia aethiopica extract (XAE) or xylopic acid (XA) and selected conventional antidepressants (imipramine, fluoxetine, and venlafaxine) in mice. Methods. Dried, powdered fruits of Xylopia aethiopica were cold macerated in 70% ethanol to obtain XAE. XA was isolated by cold macerating dried fruits of Xylopia aethiopica in petroleum ether, crystallising impure XA with ethyl acetate, and purifying XA crystals with 96% ethanol. Pharmacodynamic interaction was assessed via isobolographic analysis of tail suspension tests of the agents individually and in their respective combinations. Pharmacokinetic interaction was assessed by monitoring the effect of coadministrations on the plasma concentration of antidepressants and xylopic acid via HPLC analysis. Results. XAE and XA in mice showed significant antidepressant-like activity in the tail suspension test. With interaction indices less than one, synergism of antidepressant effect was observed in the Xylopia aethiopica extract/fluoxetine (γXAE/FL = 0.502), Xylopia aethiopica extract/imipramine (γXAE/IP = 0.322), Xylopia aethiopica extract/venlafaxine (γXAE/VL = 0.601), xylopic acid/imipramine (γXA/IP = 0.556), xylopic acid/venlafaxine (γXA/VL = 0.451), and xylopic acid/fluoxetine (γXA/FL = 0.298) combinations, which may be potentially due to elevation of serotonergic neurotransmission via varying mechanisms. The AUC of imipramine (AUCIP = 1966 ± 58.98 µg/ml.h) was significantly (P&lt;0.0001) reduced by Xylopia aethiopica extract (AUCIP = 1228 ± 67.40 µg/ml.h) and xylopic acid (AUCIP = 1250 ± 55.95 µg/ml.h), while the AUC of xylopic acid (AUCXA = 968.10 ± 61.22 µg/ml.h) was significantly (P&lt;0.0001) reduced by venlafaxine (AUCXA = 285.90 ± 51.92 µg/ml.h) and fluoxetine (AUCXA = 510.60 ± 44.74 µg/ml.h), possibly due to the effect of interfering agents on gastric emptying hence reducing oral absorption. Conclusion. Xylopia aethiopica extract and xylopic acid interacted synergistically with imipramine, fluoxetine, and venlafaxine and reduced the systemic circulation of imipramine.</abstract><cop>England</cop><pub>Wiley</pub><pmid>38826835</pmid><doi>10.1155/2024/9923801</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0002-0021-4231</orcidid><orcidid>https://orcid.org/0009-0007-7748-679X</orcidid><orcidid>https://orcid.org/0000-0002-6886-7570</orcidid><oa>free_for_read</oa></addata></record>
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subjects Acids
Analysis
Antidepressants
Complications and side effects
Dried fruit
Drug dosages
Drug interactions
Ethics
Fluoxetine
Imipramine
Investigations
Laboratory animals
Medical research
Pharmacodynamics
Pharmacokinetics
Serotonin
Suicides & suicide attempts
Toxicity
title Investigation of Herb-Drug Interactions between Xylopia aethiopica, Its Principal Constituent Xylopic Acid, and Antidepressants
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