{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T18:34:46Z","timestamp":1764700486971,"version":"3.46.0"},"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006701","name":"Umm Al-Qura University","doi-asserted-by":"publisher","award":["25UQU4331174GSSR01"],"award-info":[{"award-number":["25UQU4331174GSSR01"]}],"id":[{"id":"10.13039\/501100006701","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    The primary objective of our research is to investigate the gastroprotective impact of\n                    <jats:italic>Ficus. carica L.<\/jats:italic>\n                    latex extract (FCL). Metabolic profiling based on HR- LCMS for the extract led to the annotation of 20 compounds. Additionally, the gastro-protective activity of the latex extract was evaluated in vivo using male albino rats. FCL significantly alleviated the indomethacin-induced ulceration and reduced the ulcer index. Furthermore, the inflammation caused by indomethacin was seen to diminish due to the downregulation of the production of certain genes (\n                    <jats:italic>IL-6, and TNF-\u03b1, IL-1\u03b2<\/jats:italic>\n                    ). Besides, FCL considerably reduced the elevated\n                    <jats:italic>TGF-\u03b2, and IGF-1, COX-2<\/jats:italic>\n                    relative gene expression. Likewise, FCL dramatically raised\n                    <jats:italic>EGF<\/jats:italic>\n                    and\n                    <jats:italic>KGF<\/jats:italic>\n                    relative gene expression, demonstrating its beneficial impact in ulcer healing. The antioxidant ability of FCL was assessed by in vitro experiments utilizing hydrogen peroxide and superoxide radical scavenging, which demonstrated significant antioxidant capacity. Employing network pharmacology, we identified 10 hub genes central to peptic ulcer disease and conducted molecular docking studies screening interactions between FCL extract compounds and these hubs along with anti-inflammatory targets including FGFR, TGF-\u03b2R, IGFR-1R and IL-1R1 involved in ulcer healing. Additionally, an in-silico study using annotated FCL compounds highlighted Ficuseptin-C, Ficuseptin-B and Ficusin-A in the extract may contribute to its antiulcer properties. The present study highlighted the potential of FCL as a promising natural gastro-protective agent.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0333777","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T18:24:41Z","timestamp":1764699881000},"page":"e0333777","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Network pharmacology reveals Ficus. Carica. L latex as a potential therapeutic agent for gastric ulcers by modulating inflammation and promoting repair"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2789-2056","authenticated-orcid":true,"given":"Nourhan Hisham","family":"Shady","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5467-8939","authenticated-orcid":true,"given":"Mohamed","family":"Hisham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hend Samy","family":"Abdullah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sherif A.","family":"Maher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amgad","family":"Albohy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahmoud A.","family":"Elrehany","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed M.","family":"Sayed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esam S.","family":"Allehyani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manal M.","family":"Khowdiary","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3035-661X","authenticated-orcid":true,"given":"Ahmed M.","family":"Shawky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Usama Ramadan","family":"Abdelmohsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,12,2]]},"reference":[{"issue":"45","key":"pone.0333777.ref001","doi-asserted-by":"crossref","first-page":"17020","DOI":"10.3748\/wjg.v20.i45.17020","article-title":"Efficacy and safety of herbal medicines in treating gastric ulcer: a review","volume":"20","author":"W-P Bi","year":"2014","journal-title":"World J Gastroenterol"},{"issue":"3","key":"pone.0333777.ref002","first-page":"116","article-title":"Antiulcer properties of herbal drugs: a review","volume":"8","author":"D Bhoumik","year":"2017","journal-title":"Int J Biomed Res"},{"issue":"57","key":"pone.0333777.ref003","doi-asserted-by":"crossref","first-page":"34788","DOI":"10.1039\/D0RA06104B","article-title":"Antiulcer secondary metabolites from Elaeocarpus grandis, family Elaeocarpaceae, supported by in silico studies","volume":"10","author":"RT Mohie El-Dien","year":"2020","journal-title":"RSC Adv"},{"issue":"1","key":"pone.0333777.ref004","first-page":"52","article-title":"Herbal approach to peptic ulcer disease-review","volume":"1","author":"VK Bansal","year":"2009","journal-title":"J Biosci Tech"},{"issue":"3","key":"pone.0333777.ref005","doi-asserted-by":"crossref","DOI":"10.22270\/jddt.v6i3.1210","article-title":"Herbal treatment alternatives for peptic ulcer disease","volume":"6","author":"S Tripathy","year":"2016","journal-title":"J Drug Delivery Ther"},{"issue":"7","key":"pone.0333777.ref006","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.3390\/molecules23071751","article-title":"Antiulcer Agents: From Plant Extracts to Phytochemicals in Healing Promotion","volume":"23","author":"M Sharifi-Rad","year":"2018","journal-title":"Molecules"},{"key":"pone.0333777.ref007","first-page":"297","article-title":"Pharmacology of traditional herbal medicines and their active principles used in the treatment of peptic ulcer, diarrhoea and inflammatory bowel disease","volume":"14","author":"BP Kota","year":"2012","journal-title":"New Adv Basic Clin Gastroenterol"},{"issue":"6","key":"pone.0333777.ref008","first-page":"270","article-title":"Plants and phytochemicals for peptic ulcer: An overview","volume":"3","author":"S Sen","year":"2009","journal-title":"Pharmacognosy Reviews"},{"key":"pone.0333777.ref009","doi-asserted-by":"crossref","DOI":"10.5772\/intechopen.86562","article-title":"Phytochemical Composition, Antioxidant Potential, and Medicinal Significance of Ficus","volume-title":"Modern Fruit Industry","author":"H Nawaz","year":"2020"},{"issue":"2","key":"pone.0333777.ref010","article-title":"Estimation of nutritional, phytochemical, antioxidant and antibacterial activity of dried fig (Ficus carica)","volume":"3","author":"N Soni","year":"2014","journal-title":"Journal of Pharmacognosy and Phytochemistry"},{"issue":"11","key":"pone.0333777.ref011","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.3109\/13880209.2014.892515","article-title":"Traditional uses, phytochemistry and pharmacology of Ficus carica: a review","volume":"52","author":"SB Badgujar","year":"2014","journal-title":"Pharm Biol"},{"key":"pone.0333777.ref012","doi-asserted-by":"crossref","first-page":"1","DOI":"10.9734\/IJBCRR\/2016\/29029","article-title":"Phytochemistry and ethnopharmacology of Ficus carica","volume":"14","author":"A Bouyahya","year":"2016","journal-title":"Int J Biochem Res Rev"},{"issue":"20","key":"pone.0333777.ref013","doi-asserted-by":"crossref","first-page":"10855","DOI":"10.1021\/jf1031185","article-title":"Further insight into the latex metabolite profile of Ficus carica","volume":"58","author":"AP Oliveira","year":"2010","journal-title":"J Agric Food Chem"},{"issue":"4","key":"pone.0333777.ref014","first-page":"272","article-title":"The Effect of Fig Tree Latex (Ficus carica) on Stomach Cancer Line","volume":"13","author":"SA Hashemi","year":"2011","journal-title":"Iran Red Crescent Med J"},{"issue":"6","key":"pone.0333777.ref015","doi-asserted-by":"crossref","first-page":"3393","DOI":"10.1021\/jf9039759","article-title":"Chemical assessment and in vitro antioxidant capacity of Ficus carica latex","volume":"58","author":"AP Oliveira","year":"2010","journal-title":"J Agric Food Chem"},{"issue":"2","key":"pone.0333777.ref016","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.hermed.2016.03.002","article-title":"Collegenase activity in fig latex could contribute to its efficacy in ethnomedicinal preparations","volume":"6","author":"BG Raskovic","year":"2016","journal-title":"Journal of Herbal Medicine"},{"key":"pone.0333777.ref017","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.bcp.2019.02.011","article-title":"Time-dependent course of gastric ulcer healing and molecular markers profile modulated by increased gastric mucosal content of carbon monoxide released from its pharmacological donor","volume":"163","author":"K Magierowska","year":"2019","journal-title":"Biochem Pharmacol"},{"issue":"1","key":"pone.0333777.ref018","doi-asserted-by":"crossref","first-page":"40","DOI":"10.4291\/wjgp.v5.i1.40","article-title":"Quality of healing of gastric ulcers: Natural products beyond acid suppression","volume":"5","author":"N Kangwan","year":"2014","journal-title":"World J Gastrointest Pathophysiol"},{"key":"pone.0333777.ref019","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.lfs.2017.09.016","article-title":"Gastroprotective effect of aucubin against ethanol-induced gastric mucosal injury in mice","volume":"189","author":"Y Yang","year":"2017","journal-title":"Life Sci"},{"issue":"15","key":"pone.0333777.ref020","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.3390\/foods11152288","article-title":"Mayonnaise Enriched with Flaxseed Oil: Omega-3 Fatty Acids Content, Sensory Quality and Stability during the Storage","volume":"11","author":"M El-Waseif","year":"2022","journal-title":"Foods"},{"issue":"1","key":"pone.0333777.ref021","first-page":"20","article-title":"Effect of polaprezinc on impaired healing of chronic gastric ulcers in adjuvant-induced arthritic rats--role of insulin-like growth factors (IGF)-1","volume":"7","author":"S Kato","year":"2001","journal-title":"Med Sci Monit"},{"issue":"5","key":"pone.0333777.ref022","doi-asserted-by":"crossref","DOI":"10.1152\/ajplung.90360.2008","article-title":"P2X2 receptors differentiate placodal vs. neural crest C-fiber phenotypes innervating guinea pig lungs and esophagus","volume":"295","author":"K Kwong","year":"2008","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"pone.0333777.ref023","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1046\/j.1365-2184.35.s1.8.x","article-title":"The effects of keratinocyte growth factor in preclinical models of mucositis","volume":"35","author":"CL Farrell","year":"2002","journal-title":"Cell Prolif"},{"issue":"1","key":"pone.0333777.ref024","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jphs.2016.05.011","article-title":"Preventive effect of Gardenia jasminoides on HCl\/ethanol induced gastric injury in mice","volume":"133","author":"S Chen","year":"2017","journal-title":"J Pharmacol Sci"},{"issue":"5","key":"pone.0333777.ref025","first-page":"5135","article-title":"Insect tea attenuates hydrochloric acid and ethanol-induced mice acute gastric injury","volume":"14","author":"X Zhao","year":"2017","journal-title":"Exp Ther Med"},{"issue":"10","key":"pone.0333777.ref026","first-page":"2763","article-title":"Angiotensin I-converting enzyme inhibitors derived from Ficus carica.","volume":"53","author":"S Maruyama","year":"1989","journal-title":"Agricultural and Biological Chemistry"},{"issue":"24","key":"pone.0333777.ref027","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1016\/S0040-4039(01)83898-3","article-title":"Ficine, a novel flavonoidal alkaloid from Ficus pantoniana","author":"SR Johns","year":"1965","journal-title":"Tetrahedron Lett"},{"key":"pone.0333777.ref028","unstructured":"Kaiser R. New natural products of structural and olfactory interest identified in fig leaf absolute (Ficus carica L.). In: Progress in Essential Oil Research: Proceedings of the International Symposium on Essential Oils. Holzminden\/Neuhaus, Federal Republic of Germany; 2019. 227\u201340."},{"key":"pone.0333777.ref029","article-title":"Chemotaxonomic Diversity of Three Ficus Species: Their Discrimination Using Chemometric Analysis and Their Role in Combating Oxidative Stress","volume":"13","author":"N Al-Musayeib","year":"2017","journal-title":"Pharmacogn Mag"},{"issue":"5","key":"pone.0333777.ref030","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.jsps.2013.12.010","article-title":"Phytochemical and pharmacological study of Ficus palmata growing in Saudi Arabia","volume":"22","author":"SI Alqasoumi","year":"2014","journal-title":"Saudi Pharm J"},{"key":"pone.0333777.ref031","unstructured":"Ahmad MZ, Ali M, Srjajb Mir PS. Anti-diabetic activity of Ficus carica L. stem barks and isolation of two new flavonol esters from the plant by using spectroscopical techniques. 2013;3(18):22\u20138."},{"key":"pone.0333777.ref032","doi-asserted-by":"crossref","unstructured":"Sultana S, et al. Chemical constituents from the aerial roots of Ficus benghalensis L., leaves of Nyctanthes arbor-tristis L. and roots of Verbesina encelioides (Cav.) Benth. et Hook. f. 2018:16\u201326.","DOI":"10.20510\/ukjpb\/6\/i6\/179229"},{"issue":"4","key":"pone.0333777.ref033","first-page":"193","article-title":"Plant profile of Ficus religosa: A review","volume":"7","author":"RKJR Jangde","year":"2015","journal-title":"Journal of Science and Technology"},{"issue":"8","key":"pone.0333777.ref034","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.1016\/S0031-9422(00)84728-7","article-title":"Neobetanin: A new natural plant constituent","volume":"26","author":"D Strack","year":"1987","journal-title":"Phytochemistry"},{"issue":"12","key":"pone.0333777.ref035","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1055\/s-2005-873163","article-title":"Cytotoxic flavonoids and new chromenes from Ficus formosana f. formosana","volume":"71","author":"Y-W Sheu","year":"2005","journal-title":"Planta Med"},{"issue":"3","key":"pone.0333777.ref036","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1021\/np960683p","article-title":"Two New Isoflavones from the Bark of Ficus microcarpa","volume":"60","author":"Y-C Li","year":"1997","journal-title":"J Nat Prod"},{"issue":"7","key":"pone.0333777.ref037","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1080\/10286020500208576","article-title":"Water-soluble constituents from aerial roots of Ficus microcarpa","volume":"8","author":"M-A Ouyang","year":"2006","journal-title":"J Asian Nat Prod Res"},{"issue":"12","key":"pone.0333777.ref038","doi-asserted-by":"crossref","first-page":"2401","DOI":"10.3987\/COM-02-9615","article-title":"Phenanthroindolizidine Alkaloids and Their Cytotoxicity from the Leaves of Ficus septica","volume":"57","author":"P-L Wu","year":"2002","journal-title":"Heterocycles"},{"issue":"8","key":"pone.0333777.ref039","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1016\/S0031-9422(98)00326-4","article-title":"A monoterpenoid and two simple phenols from heartwood of Ficus microcarpa","volume":"49","author":"Y Li","year":"1998","journal-title":"Phytochemistry"},{"issue":"12","key":"pone.0333777.ref040","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.3987\/COM-95-7213","article-title":"Ficusins A and B, Two New Cyclic-Monoterpene-substituted Isoflavones from Ficus septica Barm. F.","volume":"41","author":"T Nomura","year":"1995","journal-title":"Heterocycles"},{"issue":"7","key":"pone.0333777.ref041","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1021\/np050095o","article-title":"Phenanthroindolizidine alkaloids from the stems of Ficus septica","volume":"68","author":"AG Damu","year":"2005","journal-title":"J Nat Prod"},{"issue":"3","key":"pone.0333777.ref042","first-page":"354","article-title":"Anti-ulcer activity of Ficus religiosa stem bark ethanolic extract in rats","volume":"5","author":"SAK Mohammed","year":"2011","journal-title":"Journal of Medicinal Plants Research"},{"issue":"4","key":"pone.0333777.ref043","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.jams.2013.07.003","article-title":"Assessment of the antiulcer potential of Moringa oleifera root-bark extract in rats","volume":"6","author":"MK Choudhary","year":"2013","journal-title":"J Acupunct Meridian Stud"},{"issue":"5","key":"pone.0333777.ref044","doi-asserted-by":"crossref","first-page":"644","DOI":"10.3390\/antiox10050644","article-title":"Antiulcer Potential of Olea europea L. cv. Arbequina Leaf Extract Supported by Metabolic Profiling and Molecular Docking","volume":"10","author":"A Musa","year":"2021","journal-title":"Antioxidants (Basel)"},{"issue":"7","key":"pone.0333777.ref045","article-title":"Antiulcer potential of Psidium guajava seed extract supported by metabolic profiling and molecular docking","volume":"11","author":"NH Shady","year":"2022","journal-title":"Antioxidants (Basel)"},{"issue":"3","key":"pone.0333777.ref046","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/s13105-013-0241-z","article-title":"Effect of selenium and grape seed extract on indomethacin-induced gastric ulcers in rats","volume":"69","author":"AM Abbas","year":"2013","journal-title":"J Physiol Biochem"},{"issue":"2","key":"pone.0333777.ref047","doi-asserted-by":"crossref","first-page":"211509","DOI":"10.1098\/rsos.211509","article-title":"Anti-cancer and antimicrobial potential of five soil Streptomycetes: a metabolomics-based study","volume":"9","author":"N Osama","year":"2022","journal-title":"R Soc Open Sci"},{"key":"pone.0333777.ref048","doi-asserted-by":"crossref","first-page":"21146","DOI":"10.1038\/srep21146","article-title":"BATMAN-TCM: a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine","volume":"6","author":"Z Liu","year":"2016","journal-title":"Sci Rep"},{"key":"pone.0333777.ref049","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkaa1100","article-title":"UniProt: the universal protein knowledgebase in 2021","volume":"49","author":"UniProt Consortium","year":"2021","journal-title":"Nucleic Acids Res"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0333777","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T18:24:50Z","timestamp":1764699890000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0333777"}},"subtitle":[],"editor":[{"given":"Hamida Hamdi Mohammed","family":"Ismail","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,12,2]]},"references-count":49,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0333777","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,2]]}}}