{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T04:59:04Z","timestamp":1785214744184,"version":"3.55.0"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background and purpose:<\/jats:title>\n                    <jats:p>\n                      Natural products are valuable sources of anticancer agents. This study investigated the phytochemical composition of\n                      <jats:italic toggle=\"yes\">Diarthron lessertii<\/jats:italic>\n                      shoot extract and evaluated the anticancer potential of its isolated phenolic constituents.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental approach:<\/jats:title>\n                    <jats:p>Phenolic compounds were isolated using chromatographic techniques and identified by one- and two-dimensional NMR spectroscopy and ESI-MS analysis. Cytotoxicity against HeLa cervical cancer cells was assessed using the MTT assay. A luciferase reporter assay evaluated the effect of the most active compound on FOXO3a was examined through molecular docking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings\/Results:<\/jats:title>\n                    <jats:p>\n                      Nine phenolic compounds were isolated and characterized from\n                      <jats:italic toggle=\"yes\">D. lessertii<\/jats:italic>\n                      , including two lignans (epinortrachelogenin and isolariciresinol), one biflavonoid (stelleranol), one bicoumarin (daphnoretin), and five flavonoids (genkwanin, apigenin 7,4\u2019-dimethyl ether, naringenin, apigenin, and dihydrokaempferol). Among the isolated compounds, epinortrachelogenin (compound\n                      <jats:bold>1<\/jats:bold>\n                      ) showed the strongest cytotoxic activity against HeLa cells, with an IC\n                      <jats:sub>50<\/jats:sub>\n                      value of 80.37 \u00b1 4.72 \u03bcM. In luciferase assays, compound\n                      <jats:bold>1<\/jats:bold>\n                      selectively activated FOXO3a, reaching 2274 relative luminescence units at 100 pM. Molecular docking further supported these findings, revealing favorable binding of compound\n                      <jats:bold>1<\/jats:bold>\n                      within the FOXO3a binding pocket.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and implications:<\/jats:title>\n                    <jats:p>Epinortrachelogenin exhibited notable cytotoxicity and selective FOXO3a activation, supported by docking analysis. These findings identify this lignan as a promising lead compound for the development of FOXO3a-targeted anticancer agents.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/rps.rps_233_25","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T04:00:09Z","timestamp":1785124809000},"page":"481-491","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Phenolic compounds from Diarthron lessertii: isolation, cytotoxicity, and interaction with cancer signaling pathway, FOXO3a"],"prefix":"10.4103","volume":"21","author":[{"given":"Hussein","family":"Biganeh","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morteza","family":"Sadeghi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Sa.C., Islamic Azad University, Sanandaj, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehran","family":"Miroliaei","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahnaz","family":"Khanavi","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa","family":"Ghanadian","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran"},{"name":"International Center for Interdisciplinary Research in Sciences (ICIRS), The University of Lahore, Lahore, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"issue":"1","key":"R1-20260728","doi-asserted-by":"crossref","first-page":"233","DOI":"10.3390\/molecules27010233","article-title":"Role of phenolic compounds in human disease: current knowledge and future prospects","volume":"27","author":"Rahman","year":"2021","journal-title":"Molecules"},{"issue":"3","key":"R2-20260728","doi-asserted-by":"crossref","first-page":"e09094","DOI":"10.1016\/j.heliyon.2022.e09094","article-title":"Reinforcing the bulwark: unravelling the efficient applications of plant phenolics and tannins against environmental stresses","volume":"8","author":"Dehghanian","year":"2022","journal-title":"Heliyon"},{"issue":"5","key":"R3-20260728","doi-asserted-by":"crossref","first-page":"422","DOI":"10.4103\/1735-5362.236835","article-title":"Flavone constituents of Phlomis bruguieri Desf with cytotoxic activity against MCF-7 breast cancer cells","volume":"13","author":"Sajjadi","year":"2018","journal-title":"Res Pharm Sci"},{"issue":"8","key":"R4-20260728","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.2174\/1567201819666220823155526","article-title":"Nanoformulations of plant-derived compounds as emerging therapeutic approach for colorectal cancer","volume":"20","author":"Biganeh","year":"2023","journal-title":"Curr Drug Deliv"},{"key":"R5-20260728","doi-asserted-by":"crossref","first-page":"106812","DOI":"10.1016\/j.phrs.2023.106812","article-title":"Phenolic metabolites as therapeutic in inflammation and neoplasms: molecular pathways explaining their efficacy","volume":"193","author":"Liu","year":"2023","journal-title":"Pharmacol Res"},{"issue":"10","key":"R6-20260728","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.3390\/plants10102199","article-title":"DNA barcoding of two Thymelaeaceae species: Daphne mucronata Royle and Thymelaea hirsuta (L.) 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