{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T01:16:34Z","timestamp":1768266994284,"version":"3.49.0"},"reference-count":55,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"FCT\/MCTES","doi-asserted-by":"publisher","award":["UIDB\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT\/MCTES","doi-asserted-by":"publisher","award":["UIDP\/50006\/2020"],"award-info":[{"award-number":["UIDP\/50006\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT\/MCTES","doi-asserted-by":"publisher","award":["PTDC\/ASP-AGR\/30154\/2017 (POCI-01-0145-FEDER-030154)"],"award-info":[{"award-number":["PTDC\/ASP-AGR\/30154\/2017 (POCI-01-0145-FEDER-030154)"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"COMPETE 2020 program, co-financed by the FEDER and the European Union","award":["UIDB\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020"]}]},{"name":"COMPETE 2020 program, co-financed by the FEDER and the European Union","award":["UIDP\/50006\/2020"],"award-info":[{"award-number":["UIDP\/50006\/2020"]}]},{"name":"COMPETE 2020 program, co-financed by the FEDER and the European Union","award":["PTDC\/ASP-AGR\/30154\/2017 (POCI-01-0145-FEDER-030154)"],"award-info":[{"award-number":["PTDC\/ASP-AGR\/30154\/2017 (POCI-01-0145-FEDER-030154)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>The present work aimed to detail the mechanisms elicited by Allophylus africanus P. Beauv. stem bark extract in human stomach cancer cells and to identify the bioactives underlying the cytotoxicity. MTT reduction and LDH leakage assays allowed characterizing the cytotoxic effects in AGS cells, which were further detailed by morphological analysis using phalloidin and Hoechst 33258. Proapoptotic mechanisms were elucidated through a mitochondrial membrane potential assay and by assessing the impact upon the activity of caspase-9 and -3. The extract displayed selective cytotoxicity against AGS cells. The absence of plasma membrane permeabilization, along with apoptotic body formation, suggested that pro-apoptotic effects triggered cell death. Intrinsic apoptosis pathway activation was verified, as mitochondrial membrane potential decrease and activation of caspase-9 and -3 were observed. HPLC-DAD profiling enabled the identification of two apigenin-di-C-glycosides, vicenin-2 (1) and apigenin-6-C-hexoside-8-C-pentoside (3), as well as three mono-C-glycosides-O-glycosylated derivatives, apigenin-7-O-hexoside-8-C-hexoside (2), apigenin-8-C-(2-rhamnosyl)hexoside (4) and apigenin-6-C-(2-rhamnosyl)hexoside (5). Isovitexin-2\u2033-O-rhamnoside (5) is the main constituent, accounting for nearly 40% of the total quantifiable flavonoid content. Our results allowed us to establish the relationship between the presence of vicenin-2 and other apigenin derivatives with the contribution to the cytotoxic effects on the presented AGS cells. Our findings attest the anticancer potential of A. africanus stem bark against gastric adenocarcinoma, calling for studies to develop herbal-based products and\/or the use of apigenin derivatives in chemotherapeutic drug development.<\/jats:p>","DOI":"10.3390\/life13020406","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T04:27:02Z","timestamp":1675225622000},"page":"406","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Allophylus africanus Stem Bark Extract Modulates the Mitochondrial Apoptotic Pathway in Human Stomach Cancer Cells"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9849-076X","authenticated-orcid":false,"given":"Vera","family":"Ribeiro","sequence":"first","affiliation":[{"name":"REQUIMTE\/LAQV, Laborat\u00f3rio de Farmacognosia, Departamento de Qu\u00edmica, Faculdade de Farm\u00e1cia, Universidade do Porto, R. Jorge Viterbo Ferreira, n\u00ba 228, 4050-313 Porto, Portugal"}]},{"given":"Federico","family":"Ferreres","sequence":"additional","affiliation":[{"name":"Department of Food Technology and Nutrition, Molecular Recognition and Encapsulation (REM) Group, Universidad Cat\u00f3lica de Murcia, UCAM, Campus Los Jer\u00f3nimos, s\/n, 30107 Murcia, Spain"}]},{"given":"Andreia","family":"Oliveira","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Laborat\u00f3rio de Farmacognosia, Departamento de Qu\u00edmica, Faculdade de Farm\u00e1cia, Universidade do Porto, R. Jorge Viterbo Ferreira, n\u00ba 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8727-9678","authenticated-orcid":false,"given":"Nelson G. M.","family":"Gomes","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Laborat\u00f3rio de Farmacognosia, Departamento de Qu\u00edmica, Faculdade de Farm\u00e1cia, Universidade do Porto, R. Jorge Viterbo Ferreira, n\u00ba 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7646-0386","authenticated-orcid":false,"given":"\u00c1ngel","family":"Gil-Izquierdo","sequence":"additional","affiliation":[{"name":"Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS (CSIC), Campus University Espinardo, P.O. Box 164, 30100 Murcia, Spain"}]},{"given":"Lu\u00edsa","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"MDS\u2014Medicamentos e Diagn\u00f3sticos em Sa\u00fade, Avenida dos Combatentes da Liberdade da P\u00e1tria, Bissau, Guinea-Bissau"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0384-7592","authenticated-orcid":false,"given":"David","family":"Pereira","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Laborat\u00f3rio de Farmacognosia, Departamento de Qu\u00edmica, Faculdade de Farm\u00e1cia, Universidade do Porto, R. Jorge Viterbo Ferreira, n\u00ba 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0740-4396","authenticated-orcid":false,"given":"Patr\u00edcia","family":"Valent\u00e3o","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Laborat\u00f3rio de Farmacognosia, Departamento de Qu\u00edmica, Faculdade de Farm\u00e1cia, Universidade do Porto, R. Jorge Viterbo Ferreira, n\u00ba 228, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,1]]},"reference":[{"key":"ref_1","first-page":"664","article-title":"The Ethnobotany, Phytochemistry and Biological Properties of Allophylus Species Used in Traditional Medicine: A Review","volume":"5","author":"Chavan","year":"2016","journal-title":"World J. Pharm. Pharm. 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