{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T23:45:23Z","timestamp":1785887123278,"version":"3.56.0"},"reference-count":80,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    The worldwide health impact of Type 2 diabetes mellitus (T2DM) is marked by the dysregulation of glucose metabolism caused by \u03b1-glucosidase-mediated carbohydrate degradation and pancreatic \u03b2-cell apoptosis through caspase-3 activation. This study aimed to thoroughly investigate the potential roles and mechanisms of\n                    <jats:italic>Ficus hispida<\/jats:italic>\n                    fruits methanolic extract (FhME) and its phytoconstituents in combating T2DM by experimental and computational methods. In-vitro investigations demonstrated that, FhME exhibited notable \u03b1-glucosidase inhibitory activity compared to acarbose, as indicated by its low IC\n                    <jats:sub>50<\/jats:sub>\n                    value of 850 \u00b5g\/mL. Furthermore, phytochemical analysis of FhME using the HPLC-DAD technique, combined with a review of previous literature, identified and quantified a total of 26 polyphenolic compounds. The network pharmacological investigation of FhME phytoconstituents identified 70 target genes associated with T2DM, where caspase-3 emerged as a key target. GO enrichment analysis, conducted using SRplot, highlighted key pathways, including apoptosis, lipid and atherosclerosis, and chemical carcinogenesis-receptor activation. Subsequently, molecular docking of caspase-3 with phytochemicals demonstrated strong binding affinity. Post-docking MM-GBSA study identified alpinumisoflavone and chlorogenic acid as exceptionally stable compounds. Molecular dynamics simulations conducted over 200 ns demonstrated that gallic acid and alpinumisoflavone produced the most stable complexes with caspase-3. These findings designate\n                    <jats:italic>F. hispida<\/jats:italic>\n                    fruits as a potential natural medicinal agent for Type 2 diabetes treatment, functioning through dual mechanisms of \u03b1-glucosidase inhibition and caspase-3 modulation of the apoptotic signaling pathway of the beta cells.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0337465","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T18:25:01Z","timestamp":1764613501000},"page":"e0337465","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mechanistic insight into the antidiabetic effects of Ficus hispida fruits: Inhibition of intestinal glucose absorption and pancreatic beta-cell apoptosis"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4512-8142","authenticated-orcid":true,"given":"Nusaiba","family":"Jahan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0936-6653","authenticated-orcid":true,"given":"Noimul Hasan","family":"Siddiquee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rifayat Ara Khanom","family":"Riva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0336-0435","authenticated-orcid":true,"given":"Nur Uddin","family":"Chowdhury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5904-5391","authenticated-orcid":true,"given":"Marjanur Rahman","family":"Bhuiyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khondoker Shahin","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemayet","family":"Hossain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9605-7703","authenticated-orcid":true,"given":"Sadikur Rahman","family":"Shuvo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3342-4809","authenticated-orcid":true,"given":"AFM. Shahid Ud","family":"Daula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"key":"pone.0337465.ref001","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.diabres.2018.02.023","article-title":"IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045","volume":"138","author":"NH Cho","year":"2018","journal-title":"Diabetes Res Clin Pract"},{"issue":"4","key":"pone.0337465.ref002","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2024-092951","article-title":"Interplay of health-related quality of life and comorbidities in people with type 2 diabetes mellitus treated in primary care settings in Austria: a countrywide cross-sectional study","volume":"15","author":"H Sourij","year":"2025","journal-title":"BMJ Open"},{"issue":"5","key":"pone.0337465.ref003","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1093\/gerona\/glaa172","article-title":"Impact of Diabetes on Life and Healthy Life Expectancy Among Older Women","volume":"76","author":"BL Wubishet","year":"2021","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"pone.0337465.ref004","doi-asserted-by":"crossref","first-page":"110708","DOI":"10.1016\/j.biopha.2020.110708","article-title":"Type II diabetes mellitus: a review on recent drug based therapeutics","volume":"131","author":"S Padhi","year":"2020","journal-title":"Biomed Pharmacother"},{"issue":"8","key":"pone.0337465.ref005","doi-asserted-by":"crossref","first-page":"806","DOI":"10.3390\/ph14080806","article-title":"Pharmaceutical Drugs and Natural Therapeutic Products for the Treatment of Type 2 Diabetes Mellitus","volume":"14","author":"J Blahova","year":"2021","journal-title":"Pharmaceuticals (Basel)"},{"issue":"20","key":"pone.0337465.ref006","first-page":"2722","article-title":"Recent Updates on Phytoconstituent Alpha-Glucosidase Inhibitors: An Approach towards the Treatment of Type Two Diabetes","volume":"11","author":"H Kashtoh","year":"2022","journal-title":"Plants (Basel)"},{"issue":"1","key":"pone.0337465.ref007","doi-asserted-by":"crossref","first-page":"81","DOI":"10.3390\/antiox10010081","article-title":"Plant Extracts for Type 2 Diabetes: From Traditional Medicine to Modern Drug Discovery","volume":"10","author":"J Lee","year":"2021","journal-title":"Antioxidants (Basel)"},{"key":"pone.0337465.ref008","doi-asserted-by":"crossref","first-page":"101282","DOI":"10.1016\/j.fochx.2024.101282","article-title":"Hypoglycemic activity in vivo and in vitro of the Lotus (Nelumbo nucifera Gaertn.) seed skin (testa) phenolic-rich extracts","volume":"22","author":"H Xu","year":"2024","journal-title":"Food Chem X"},{"issue":"10","key":"pone.0337465.ref009","first-page":"1406","article-title":"Hypoglycemic Effects of Extracts Obtained from Endemic Betonica bulgarica Degen and Nei\u010d","volume":"13","author":"I Slavova","year":"2024","journal-title":"Plants (Basel)"},{"key":"pone.0337465.ref010","doi-asserted-by":"crossref","first-page":"112204","DOI":"10.1016\/j.jep.2019.112204","article-title":"Traditional uses, phytochemistry, and pharmacology of Ficus hispida L.f.: A review","volume":"248","author":"J-X Cheng","year":"2020","journal-title":"J Ethnopharmacol"},{"key":"pone.0337465.ref011","first-page":"144","article-title":"A Systematic Review on Pharmacological Actions of Ficus hispida","author":"A DK","year":"2022","journal-title":"IJPSRR"},{"issue":"6","key":"pone.0337465.ref012","doi-asserted-by":"crossref","first-page":"759","DOI":"10.18203\/2319-2003.ijbcp20212090","article-title":"A phytochemical and pharmacognostic approach of Ficus hispida Linn: a review","volume":"10","author":"A Choudhury","year":"2021","journal-title":"Int J Basic Clin Pharmacol"},{"issue":"4","key":"pone.0337465.ref013","first-page":"222","article-title":"Hypoglycemic activity of Ficus hispida (bark) in normal and diabetic albino rats","volume":"36","author":"R Ghosh","year":"2004","journal-title":"Indian Journal of Pharmacology"},{"key":"pone.0337465.ref014","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.jep.2017.12.045","article-title":"A role of Ficus species in the management of diabetes mellitus: A review","volume":"215","author":"P Deepa","year":"2018","journal-title":"J Ethnopharmacol"},{"key":"pone.0337465.ref015","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jep.2017.11.016","article-title":"Potential cancer chemopreventive and anticancer constituents from the fruits of Ficus hispida L.f. 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