{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T10:46:28Z","timestamp":1779014788218,"version":"3.51.4"},"reference-count":37,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,26]],"date-time":"2022-06-26T00:00:00Z","timestamp":1656201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deanship of Scientific Research (DSR) at King Abdulaziz University, Jeddah, Saudi Arabia","award":["G-549-166-1439"],"award-info":[{"award-number":["G-549-166-1439"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Medicinal plants are widely used in folk medicine to treat various diseases. Thonningia sanguinea Vahl is widespread in African traditional medicine, and exhibits antioxidant, antibacterial, antiviral, and anticancer activities. T. sanguinea is a source of phytomedicinal agents that have previously been isolated and structurally elucidated. Herein, gas chromatography combined with tandem mass spectrometry (GC-MS\/MS) was used to quantify epipinoresinol, \u03b2-sitosterol, eriodictyol, betulinic acid, and secoisolariciresinol contents in the methanolic crude extract and its ethyl acetate fraction for the first time. The ethyl acetate fraction was rich in epipinoresinol, eriodictyol, and secoisolariciresinol at concentrations of 2.3, 3.9, and 2.4 mg\/g of dry extract, respectively. The binding interactions of these compounds with the epidermal growth factor receptor (EGFR) were computed using a molecular docking study. The results revealed that the highest binding affinities for the EGFR signaling pathway were attributed to eriodictyol and secoisolariciresinol, with good binding energies of \u221219.93 and \u221216.63 Kcal\/mol, respectively. These compounds formed good interactions with the key amino acid Met 769 as the co-crystallized ligand. So, the ethyl acetate fraction of T. sanguinea is a promising adjuvant therapy in cancer treatments.<\/jats:p>","DOI":"10.3390\/molecules27134109","type":"journal-article","created":{"date-parts":[[2022,6,26]],"date-time":"2022-06-26T21:01:41Z","timestamp":1656277301000},"page":"4109","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["GC-MS\/MS Quantification of EGFR Inhibitors, \u03b2-Sitosterol, Betulinic Acid, (+) Eriodictyol, (+) Epipinoresinol, and Secoisolariciresinol, in Crude Extract and Ethyl Acetate Fraction of Thonningia sanguinea"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3799-0581","authenticated-orcid":false,"given":"Sameh S.","family":"Elhady","sequence":"first","affiliation":[{"name":"Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8479-5733","authenticated-orcid":false,"given":"Elsayed A.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9291-8940","authenticated-orcid":false,"given":"Marwa S.","family":"Goda","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4454-6390","authenticated-orcid":false,"given":"Mohamed S.","family":"Nafie","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, Suez Canal University, Ismailia 41522, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2137-2941","authenticated-orcid":false,"given":"Hanan","family":"Samir","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt"},{"name":"Medical Administration, Students Hospital, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reem M.","family":"Diri","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdulrahman M.","family":"Alahdal","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6231-5815","authenticated-orcid":false,"given":"Ama Kyeraa","family":"Thomford","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Allied Health Sciences, University of Cape Coast, Cape Coast 03321, Ghana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alaa","family":"El Gindy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1386-5401","authenticated-orcid":false,"given":"Ghada M.","family":"Hadad","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jihan M.","family":"Badr","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reda F. A.","family":"Abdelhameed","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Galala University, New Galala 43713, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1002\/jssc.201900811","article-title":"Purification of Thonningianins A and B and Four Further Derivatives from Thonningia sanguinea By One- and Two-Dimensional Centrifugal Partition Chromatography","volume":"43","author":"Pompermaier","year":"2019","journal-title":"J. Sep. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"21002","DOI":"10.1039\/C8RA03913E","article-title":"Chemical Studies on The Parasitic Plant Thonningia Sanguinea Vahl","volume":"8","author":"Thomford","year":"2018","journal-title":"RSC Adv."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/S0306-3623(98)00238-9","article-title":"Free-Radical Scavenging Action of Medicinal Herbs from Ghana Thonningia Sanguinea on Experimentally Induced Liver Injuries","volume":"32","author":"Gyamfi","year":"1999","journal-title":"Gen. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/S0367-326X(99)00124-0","article-title":"Antimicrobial Properties of Thonningia Sanguinea Root Extracts","volume":"71","author":"Ohiri","year":"2000","journal-title":"Fitoterapia"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1021\/np990396w","article-title":"Thonningianins A and B, New Antioxidants from The African Medicinal Herb Thonningia sanguinea","volume":"63","author":"Ohtani","year":"2000","journal-title":"J. Nat. Prod."},{"key":"ref_6","first-page":"301","article-title":"Anti Staphylococcus aureus Activity of The Aqueous Extract and Hexanic Fraction of Thonningia sanguinea (Cote ivoire)","volume":"7","author":"Rubens","year":"2015","journal-title":"Int. J. Pharm. Phytochem."},{"key":"ref_7","first-page":"779","article-title":"Antibacterial Activity of The Aqueous Extract of Thonningia sanguinea Against Extended-Spectrum-\u03b2-Lactamases (ESBL) Producing Escherichia coli and Klebsiella pneumoniae Strains","volume":"6","author":"Dinzedi","year":"2007","journal-title":"Trop. J. Pharm. Res."},{"key":"ref_8","first-page":"155","article-title":"Antibacterial Activity of Thonningia sanguinea Against Some Multi-Drug Resistant Strains of Salmonella enterica","volume":"7","author":"Coulibaly","year":"2007","journal-title":"Afr. Health Sci."},{"key":"ref_9","first-page":"6247","article-title":"In Vitro Anticoccidial Activity of Thonningia sanguinea Extract on Eimeria tenella and Eimeria necatrix Sporozoites Cells","volume":"6","author":"Alassane","year":"2012","journal-title":"Afr. J. Microbiol. Res."},{"key":"ref_10","first-page":"47","article-title":"Efficacy of Thonningia sanguinea Vahl. (Balanophoraceae) Root Extract Against Plasmodium berghei, Plasmodium chabaudi, Inflammation and Nociception in Mice","volume":"2","author":"Jigam","year":"2012","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1177\/096032719801700802","article-title":"Medicinal Herb, Thonningia sanguinea Protects Against Aflatoxin B1 Acute Hepatotoxicity in Fischer 344 Rats","volume":"17","author":"Gyamfi","year":"1998","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1021\/acs.jnatprod.8b00450","article-title":"Dihydrochalcone Glucosides from The Subaerial Parts of Thonningia sanguinea and Their In Vitro PTP1B Inhibitory Activities","volume":"81","author":"Pompermaier","year":"2018","journal-title":"J. Nat. Prod."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Abdelhameed, R.F.A., Elhady, S.S., Sirwi, A., Samir, H., Ibrahim, E.A., Thomford, A.K., el Gindy, A., Hadad, G.M., Badr, J.M., and Nafie, M.S. (2021). Thonningia sanguinea Extract: Antioxidant and Cytotoxic Activities Supported by Chemical Composition and Molecular Docking Simulations. Plants, 10.","DOI":"10.3390\/plants10102156"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Vundru, S.S., Kale, R.K., and Singh, R.P. (2013). \u03b2-sitosterol induces G1 arrest and causes depolarization of mitochondrial membrane potential in breast carcinoma MDA-MB-231 cells. BMC Complement. Altern. Med., 13.","DOI":"10.1186\/1472-6882-13-280"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"481","DOI":"10.3389\/fphar.2018.00481","article-title":"Betulinic Acid Exerts Cytotoxic Activity Against Multidrug-Resistant Tumor Cells via Targeting Autocrine Motility Factor Receptor (AMFR)","volume":"9","author":"Saeed","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"446","DOI":"10.5114\/aoms.2019.85152","article-title":"Eriodictyol exerts potent anticancer activity against A549 human lung cancer cell line by inducing mitochondrial-mediated apoptosis, G2\/M cell cycle arrest and inhibition of m-TOR\/PI3K\/Akt signalling pathway","volume":"16","author":"Zhang","year":"2020","journal-title":"Arch. Med. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.jchromb.2017.03.036","article-title":"Optimized conversion of antiproliferative lignans pinoresinol and epipinoresinol: Their simultaneous isolation and identification by centrifugal partition chromatography and high performance liquid chromatography","volume":"1052","author":"Darcsi","year":"2017","journal-title":"J. Chromatogr. B."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e9163","DOI":"10.7717\/peerj.9163","article-title":"In silico and in vitro identification of secoisolariciresinol as a re-sensitizer of P-glycoprotein-dependent doxorubicin-resistance NCI\/ADR-RES cancer cells","volume":"8","author":"Morsy","year":"2020","journal-title":"Peer J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"47","DOI":"10.17159\/0379-4350\/2019\/v72a7","article-title":"Determination of Phytocomponents of Twenty-one Varieties of Smokeless Tobacco using Gas Chromatography-Mass Spectroscopy (GC-MS)","volume":"72","author":"Alhazmi","year":"2019","journal-title":"S. Afr. J. Chem."},{"key":"ref_20","first-page":"50","article-title":"GC-MS Analysis and Antimicrobial Activities of The Non-Polar Extracts of Mundulea sericea","volume":"65","author":"Mazimba","year":"2012","journal-title":"S. Afr. J. Chem."},{"key":"ref_21","first-page":"1","article-title":"Gas Chromatography-Mass Spectrometry Analysis of Marine Seagrass Thalassodendron ciliatum Collected from Red Sea","volume":"4","author":"Goda","year":"2020","journal-title":"Rec. Pharm. Biomed. Sci."},{"key":"ref_22","first-page":"1","article-title":"Chemical Profiling, Cytotoxic Activities Through Apoptosis Induction In MCF-7 Cells and Molecular Docking of Phyllostachys heterocycla Bark Nonpolar Extract","volume":"2021","author":"Abdelhameed","year":"2021","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"641","DOI":"10.3389\/fgene.2018.00641","article-title":"Secoisolariciresinol Diglucoside of Flaxseed, and Its Metabolites: Biosynthesis and Potential for Nutraceuticals","volume":"9","author":"Kezimana","year":"2018","journal-title":"Front. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1038\/sj.bjc.6601746","article-title":"Betulinic Acid Augments the Inhibitory Effects of Vincristine on Growth and Lung Metastasis of B16F10 Melanoma Cells in Mice","volume":"90","author":"Sawada","year":"2004","journal-title":"Br. J. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1002\/mnfr.200700222","article-title":"\u03b2-Sitosterol Enhances Tamoxifen Effectiveness in Breast Cancer Cells by Affecting Ceramide Metabolism","volume":"52","author":"Awad","year":"2008","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Lee, K., and Kim, D. (2019). In-Silico Molecular Binding Prediction for Human Drug Targets Using Deep Neural Multi-Task Learning. Genes, 10.","DOI":"10.3390\/genes10110906"},{"key":"ref_27","first-page":"1","article-title":"In Silico Molecular Docking and In Vitro Antidiabetic Studies of Dihydropyrimido [4, 5-a] acridin-2-amines","volume":"2014","author":"Bharathi","year":"2014","journal-title":"Bio Med. Res. Int."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"de Silva, S.F., and Alcorn, J. (2019). Flaxseed Lignans as Important Dietary Polyphenols for Cancer Prevention and Treatment: Chemistry, Pharmacokinetics, and Molecular Targets. Pharmaceuticals, 12.","DOI":"10.3390\/ph12020068"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"114","DOI":"10.3389\/fphar.2020.00114","article-title":"Eriodictyol Inhibits Proliferation, Metastasis, and Induces Apoptosis of Glioma Cells via PI3K\/Akt\/NF-\u03baB Signaling Pathway","volume":"11","author":"Li","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1677\/erc.1.00600","article-title":"Epidermal Growth Factor Receptor Inhibition Strategies in Oncology","volume":"11","author":"Harari","year":"2004","journal-title":"Endocr. Relat. Cancer."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Normanno, N., Pergameno, M., Lannaccone, A., and de Luca, A. (2012). Mechanisms of Action of EGFR Inhibitors. EGFR Inhibitors in Cancer Treatment, Future Medicine Ltd.","DOI":"10.2217\/ebo.11.305"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1093\/neuonc\/nou046","article-title":"JAK2\/STAT3 Targeted Therapy Suppresses Tumor Invasion via Disruption of the EGFRvIII\/JAK2\/STAT3 Axis and Associated Focal Adhesion in EGFRvIII-Expressing Glioblastoma","volume":"16","author":"Zheng","year":"2014","journal-title":"Neuro. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"113609","DOI":"10.1016\/j.ejmech.2021.113609","article-title":"Design, Synthesis and Evaluation of New Quinazolin-4-One Derivatives as Apoptotic Enhancers and Autophagy Inhibitors with Potent Antitumor Activity","volume":"222","author":"ElZahabi","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_34","first-page":"170","article-title":"GC\/MS Analysis and Bioactive Properties of Extracts Obtained from Clusia minor L. Leaves","volume":"62","author":"Porto","year":"2018","journal-title":"J. Mex. Chem. Soc."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"108485","DOI":"10.1016\/j.steroids.2019.108485","article-title":"Screening of Different Drug Design Tools to Predict the Mode of Action of Steroidal Derivatives as Anti-Cancer Agents","volume":"152","author":"Nafie","year":"2019","journal-title":"Steroids"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1111\/cbdd.13997","article-title":"Quinoline-based Thiazolidinone Derivatives as Potent Cytotoxic and Apoptosis-inducing Agents through EGFR Inhibition","volume":"99","author":"Nafie","year":"2022","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Abdelhameed, R.F.A., Habib, E.S., Ibrahim, A.K., Yamada, K., Abdel-Kader, M.S., Ahmed, S.A., Ibrahim, A.K., Badr, J.M., and Nafie, M.S. (2021). Chemical Constituent Profiling of Phyllostachys Heterocycla Var. Pubescens with Selective Cytotoxic Polar Fraction through EGFR Inhibition in HepG2 Cells. Molecules, 26.","DOI":"10.3390\/molecules26040940"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/13\/4109\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:38:43Z","timestamp":1760139523000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/13\/4109"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,26]]},"references-count":37,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["molecules27134109"],"URL":"https:\/\/doi.org\/10.3390\/molecules27134109","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,26]]}}}