{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:13:24Z","timestamp":1788437604246,"version":"build-2803163510"},"reference-count":24,"publisher":"American Chemical Society (ACS)","issue":"34","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20GM130456"],"award-info":[{"award-number":["P20GM130456"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008460","name":"National Center for Complementary and Integrative Health","doi-asserted-by":"publisher","award":["R21AT013164"],"award-info":[{"award-number":["R21AT013164"]}],"id":[{"id":"10.13039\/100008460","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008460","name":"National Center for Complementary and Integrative Health","doi-asserted-by":"publisher","award":["R33-AT011938"],"award-info":[{"award-number":["R33-AT011938"]}],"id":[{"id":"10.13039\/100008460","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008460","name":"National Center for Complementary and Integrative Health","doi-asserted-by":"publisher","award":["R61-AT011938"],"award-info":[{"award-number":["R61-AT011938"]}],"id":[{"id":"10.13039\/100008460","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Acacia sieberiana (syn. Vachellia sieberiana), widely used in African traditional medicine for pain, was investigated using an ethnopharmacology-guided workflow integrating LC-MS\/MS-based metabolomics and molecular networking to prioritize bioactive secondary metabolites. Fractionation of the ethanolic stem bark extract enabled targeted isolation and identification of piperine (1) and moupinamide (3) by HRMS and NMR. Moupinamide and its positional isomer (tamgermanetin) were synthesized via HATU-mediated coupling to support preliminary structure\u2013activity studies. In a capsaicin-induced mouse model, the extract significantly attenuated acute nociceptive behavior without affecting the secondary mechanical hypersensitivity. Functional screening using human iPSC-derived nociceptors in a multielectrode array (MEA) platform showed that moupinamide potently reduced neuronal firing, with reduced efficacy under high-heat conditions, suggesting a non-TRPV1-mediated mechanism. GPCR profiling of moupinamide revealed minimal receptor engagement, and further pharmacological studies demonstrated retained activity under potassium channel blockade and suppression of Nav1.7-induced hyperexcitability, consistent with voltage-gated sodium channel modulation. These findings highlight A. sieberiana-derived alkaloid amides as promising nonopioid analgesic leads and underscore the utility of metabolomics-guided discovery strategies.<\/jats:p>","DOI":"10.1021\/acsomega.6c06672","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T22:02:01Z","timestamp":1787090521000},"page":"51921-51930","source":"Crossref","is-referenced-by-count":0,"title":["Discovery and Characterization\nof Neuroactive Secondary\nMetabolites from\n                    <i>Acacia sieberiana<\/i>\n                    with Potential\nAnalgesic Properties"],"prefix":"10.1021","volume":"11","author":[{"given":"Sahar","family":"Mofidi Tabatabaei","sequence":"first","affiliation":[{"name":"University of Kentucky , , , ,","place":["Lexington, Kentucky, United States, 40506"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian Kuete","family":"Fofie","sequence":"additional","affiliation":[{"name":"University of Texas at Dallas , , , ,","place":["Richardson, Texas, United States, 75080-3021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliance Romain","family":"Fokoua","sequence":"additional","affiliation":[{"name":"University of Dschang , , P.O. Box ,","place":["Dschang, Cameroon, 67"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex Junior","family":"Kamtcha Yamdjieu","sequence":"additional","affiliation":[{"name":"University of Dschang , , P.O. Box ,","place":["Dschang, Cameroon, 67"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Walsh","sequence":"additional","affiliation":[{"name":"Anatomic Incorporated , , ,","place":["Minneapolis, Minnesota, United States, 55413"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Dussor","sequence":"additional","affiliation":[{"name":"University of Texas at Dallas , , , ,","place":["Richardson, Texas, United States, 75080-3021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5006-6927","authenticated-orcid":true,"given":"Te\u0301lesphore Benoi\u0302t","family":"Nguelefack","sequence":"additional","affiliation":[{"name":"University of Dschang , , P.O. Box ,","place":["Dschang, Cameroon, 67"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8665-1805","authenticated-orcid":true,"given":"Benedict James","family":"Kolber","sequence":"additional","affiliation":[{"name":"University of Texas at Dallas , , , ,","place":["Richardson, Texas, United States, 75080-3021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0501-2604","authenticated-orcid":true,"given":"Kevin Joseph","family":"Tidgewell","sequence":"additional","affiliation":[{"name":"University of Kentucky , , , ,","place":["Lexington, Kentucky, United States, 40506"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"issue":"11","key":"2026090307192938300_cit1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2020.e05412","article-title":"Botanicals\nfrom the leaves of Acacia sieberiana had better cytotoxic\neffects than isolated phytochemicals towards MDR cancer cell lines","volume":"6","author":"Ngaffo","year":"2020","journal-title":"Heliyon"},{"key":"2026090307192938300_cit2","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/9407962","article-title":"In Vitro\nAntibacterial\nPotential of Extracts of Sterculia africana, Acacia sieberiana, and Cassia abbreviata ssp. abbreviata Used by Yellow Baboons (Papio\ncynocephalus) for Possible Self-Medication in Mikumi National Park,\nTanzania","volume":"2018","author":"Kirabo","year":"2018","journal-title":"Int. J. Zool."},{"issue":"1","key":"2026090307192938300_cit3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.15413\/ajpp.2015.0101","article-title":"Phytochemical Screening\nand Antidiarrheal Evaluation\nof Acetone Extract of Acacia sieberiana var woodii\n(Fabaceae) stem bark in Wistar rats","volume":"3","author":"Zeukoo","year":"2015","journal-title":"Acad. J.\nPharm. Pharmacol."},{"key":"2026090307192938300_cit4","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.959661","article-title":"Acacia sieberiana (Fabaceae) attenuates paracetamol and Bile Duct Ligation-Induced\nhepatotoxicity via modulation of biochemical and oxidative stress\nbiomarkers","volume":"13","author":"Watafua","year":"2022","journal-title":"Front. Pharmacol."},{"issue":"4","key":"2026090307192938300_cit5","first-page":"799","article-title":"Antidiarrheal evaluation\nof aqueous and ethanolic leaf extracts of Acacia sieberiana DC. 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