{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:31:23Z","timestamp":1791919883048,"version":"4.3.4"},"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T00:00:00Z","timestamp":1646265600000},"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>In folklore, <jats:italic>Heritiera fomes<\/jats:italic> (<jats:italic>H<\/jats:italic>. <jats:italic>fomes<\/jats:italic>) has been extensively used in treatment of various ailments such as diabetes, cardiac and hepatic disorders. The present study aimed to elucidate the antidiabetic actions of hot water extract of <jats:italic>H<\/jats:italic>. <jats:italic>fomes<\/jats:italic> (HWHF), including effects on insulin release from BRIN BD11 cells and isolated mouse islets as well as glucose homeostasis in high-fat-fed rats. Molecular mechanisms underlying anti-diabetic activity along with isolation of active compounds were also evaluated. Non-toxic concentrations of HWHF stimulated concentration-dependent insulin release from isolated mouse islets and clonal pancreatic \u03b2-cells. The stimulatory effect was potentiated by glucose and isobutyl methylxanthine (IBMX), persisted in presence of tolbutamide or a depolarizing concentration of KCl but was attenuated by established inhibitors of insulin release such as diazoxide, verapamil, and Ca<jats:sup>2+<\/jats:sup> chelation. HWHF caused depolarization of the \u03b2-cell membrane and increased intracellular Ca<jats:sup>2+<\/jats:sup>. The extract also enhanced glucose uptake and insulin action in 3T3-L1 differentiated adipocytes cells and significantly inhibited in a dose-dependent manner starch digestion, protein glycation, DPP-IV enzyme activity, and glucose diffusion <jats:italic>in vitro<\/jats:italic>. Oral administration of HWHF (250 mg\/5ml\/kg b.w.) to high-fat fed rats significantly improved glucose tolerance and plasma insulin responses and it inhibited plasma DPP-IV activity. HWHF also decreased <jats:italic>in vivo<\/jats:italic> glucose absorption and intestinal disaccharidase activity while increasing gastrointestinal motility and unabsorbed sucrose transit. Compounds were isolated from HWHF with similar molecular weights to quercitrin (C<jats:sub>21<\/jats:sub> H<jats:sub>20<\/jats:sub> O<jats:sub>11<\/jats:sub>) ranging from 447.9 to 449.9 Da which stimulated the insulin release <jats:italic>in vitro<\/jats:italic> and improved both glucose tolerance and plasma insulin responses in mice. In conclusion, <jats:italic>H<\/jats:italic>. <jats:italic>fomes<\/jats:italic> and its water-soluble phytochemicals such as quercitrin may exert antidiabetic actions mediated through a variety of mechanisms which might be useful as dietary adjunct in the management of type 2 diabetes.<\/jats:p>","DOI":"10.1371\/journal.pone.0264632","type":"journal-article","created":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T18:56:25Z","timestamp":1646333785000},"page":"e0264632","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":20,"title":["Insulin secretory and antidiabetic actions of Heritiera fomes bark together with isolation of active phytomolecules"],"prefix":"10.1371","volume":"17","author":[{"given":"Prawej","family":"Ansari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Flatt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Harriott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3991-3419","authenticated-orcid":true,"given":"Yasser H. 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Larry Jameson et al.) 898\u2013906 (W.B. Saunders, 2016).","DOI":"10.1016\/B978-0-323-18907-1.00051-2"},{"key":"pone.0264632.ref009","doi-asserted-by":"crossref","unstructured":"Zochodne DW. in Handbook of Clinical Neurology Vol. 126 (eds Douglas W. Zochodne & Rayaz A. Malik) 379\u2013399 (Elsevier, 2014).","DOI":"10.1016\/B978-0-444-53480-4.00028-X"},{"key":"pone.0264632.ref010","first-page":"331","article-title":"Type 2 diabetes: prevalence and relevance of genetic and acquired factors for its prediction","volume":"110","author":"W Rathmann","year":"2013","journal-title":"Dtsch Arztebl Int"},{"key":"pone.0264632.ref011","doi-asserted-by":"crossref","first-page":"e029280","DOI":"10.1136\/bmjopen-2019-029280","article-title":"Oral antidiabetic medication adherence and glycaemic control among patients with type 2 diabetes mellitus: a cross-sectional retrospective study in a tertiary hospital in Saudi Arabia","volume":"9","author":"B Balkhi","year":"2019","journal-title":"BMJ Open"},{"key":"pone.0264632.ref012","doi-asserted-by":"crossref","first-page":"293","DOI":"10.3390\/molecules24020293","article-title":"A review on the phytochemistry, medicinal properties and pharmacological activities of 15 selected myanmar medicinal plants","volume":"24","author":"MM Aye","year":"2019","journal-title":"Molecules"},{"key":"pone.0264632.ref013","first-page":"938543","article-title":"Pharmacological and ethnomedicinal overview of Heritiera fomes: Future Prospects","volume":"2014","author":"I Mahmud","year":"2014","journal-title":"Int Sch Res Notices"},{"key":"pone.0264632.ref014","first-page":"116","article-title":"An evaluation of antihyperglycemic and antinociceptive effects of methanol extract of Heritiera fomes Buch.-Ham. (Sterculiaceae) barks in Swiss albino mice","volume":"5","author":"M Ali","year":"2011","journal-title":"Adv Nat Appl Sci"},{"key":"pone.0264632.ref015","doi-asserted-by":"crossref","first-page":"195","DOI":"10.17348\/era.8.0.195-218","article-title":"A comparative analysis of medicinal plants used by folk medicinal healers in three districts of bangladesh and inquiry as to mode of selection of medicinal plants","volume":"8","author":"MAH Mollik","year":"2010","journal-title":"Ethnobot Res Appl"},{"key":"pone.0264632.ref016","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1007\/s11738-010-0667-7","article-title":"Metabolic diversity and bioactivity screening of mangrove plants: a review","volume":"33","author":"JK Patra","year":"2011","journal-title":"Acta Physiol Plantarum"},{"key":"pone.0264632.ref017","first-page":"59","article-title":"Chemical and biological studies of medicinal plants from the Sundarbans mangrove forest","volume":"1","author":"H Wangensteen","year":"2009","journal-title":"Adv Phytother Res"},{"key":"pone.0264632.ref018","first-page":"371","article-title":"Antioxidant and antimicrobial effects of the mangrove tree Heritiera fomes","volume":"4","author":"H Wangensteen","year":"2009","journal-title":"Nat Prod Comm"},{"key":"pone.0264632.ref019","first-page":"95","article-title":"Phytochemical and pharmacological assessment of the ethanol leaves extract of Heritiera fomes Buch. 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A. Moharram","year":"2006","journal-title":"Natural Product Research"},{"key":"pone.0264632.ref034","doi-asserted-by":"crossref","first-page":"5943","DOI":"10.1016\/S0031-9422(97)00366-X","article-title":"Three flavonol glycosides from leaves of Myrsine seguinii","volume":"46","author":"XN Zhong","year":"1997","journal-title":"Phytochemistry"},{"key":"pone.0264632.ref035","doi-asserted-by":"crossref","first-page":"25","DOI":"10.3727\/096368913X673441","article-title":"Diazoxide, a K(ATP) channel opener, prevents ischemia-reperfusion injury in rodent pancreatic islets","volume":"24","author":"Y Wang","year":"2015","journal-title":"Cell Transplant"},{"key":"pone.0264632.ref036","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/BF01223617","article-title":"The adenylate cyclase-cyclic AMP system in islets of Langerhans and its role in the control of insulin release","volume":"16","author":"GW Sharp","year":"1979","journal-title":"Diabetologia"},{"key":"pone.0264632.ref037","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s13596-019-00401-0","article-title":"Antioxidant and anti-inflammatory activity of Heritiera fomes (Buch.-Ham), a mangrove plant of the Sundarbans","volume":"20","author":"ME Islam","year":"2019","journal-title":"Adv Tradit Med"},{"key":"pone.0264632.ref038","doi-asserted-by":"crossref","first-page":"S157","DOI":"10.2337\/dc09-S302","article-title":"Skeletal muscle insulin resistance is the primary defect in type 2 diabetes","volume":"32","author":"RA DeFronzo","year":"2009","journal-title":"Diabetes Care"},{"key":"pone.0264632.ref039","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.2337\/diabetes.50.8.1901","article-title":"Defective insulin-induced GLUT4 translocation in skeletal muscle of high fat\u2013fed rats is associated with alterations in both Akt\/protein kinase B and atypical protein kinase C (zeta\/lambda) activities","volume":"50","author":"F Tremblay","year":"2001","journal-title":"Diabetes"},{"key":"pone.0264632.ref040","doi-asserted-by":"crossref","first-page":"134","DOI":"10.14196\/mjiri.31.134","article-title":"Polyphenols and their effects on diabetes management: A review","volume":"31","author":"N Aryaeian","year":"2017","journal-title":"Med J Islam Repub Iran"},{"key":"pone.0264632.ref041","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/S0006-291X(03)00720-4","article-title":"Naringenin inhibits phosphoinositide 3-kinase activity and glucose uptake in 3T3-L1 adipocytes","volume":"305","author":"AW Harmon","year":"2003","journal-title":"Biochem Biophys Res Comm"},{"key":"pone.0264632.ref042","first-page":"S817","article-title":"Rhinacanthins-rich extract enhances glucose uptake and inhibits adipogenesis in 3T3-L1 adipocytes and L6 myotubes","volume":"13","author":"MA Shah","year":"2018","journal-title":"Pharmacogn Mag"},{"key":"pone.0264632.ref043","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.2337\/diab.45.11.1489","article-title":"Glycation of insulin in the islets of Langerhans of normal and diabetic animals","volume":"45","author":"YH Abdel-Wahab","year":"1996","journal-title":"Diabetes"},{"key":"pone.0264632.ref044","doi-asserted-by":"crossref","first-page":"492","DOI":"10.2337\/diabetes.52.2.492","article-title":"Demonstration of glycated insulin in human diabetic plasma and decreased biological activity assessed by euglycemic-hyperinsulinemic clamp technique in humans","volume":"52","author":"SJ Hunter","year":"2003","journal-title":"Diabetes"},{"key":"pone.0264632.ref045","doi-asserted-by":"crossref","first-page":"793","DOI":"10.3389\/fphar.2017.00793","article-title":"Evaluation of the antioxidant and antiglycation effects of Lactarius deterrimus and Castanea sativa extracts on hepatorenal injury in streptozotocin-induced diabetic rats","volume":"8","author":"JA Jovanovi\u0107","year":"2017","journal-title":"Front Pharmacol"},{"key":"pone.0264632.ref046","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.fshw.2014.11.003","article-title":"\u03b1-Glucosidase inhibitors isolated from medicinal plants","volume":"3","author":"Z Yin","year":"2014","journal-title":"Food Sci Human Wellness"},{"key":"pone.0264632.ref047","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1080\/17450390701203907","article-title":"The content of protein, fibre and minerals of leaves of selected Acacia species indigenous to north-western Tanzania","volume":"61","author":"CD Rubanza","year":"2007","journal-title":"Arch Anim Nutr"},{"key":"pone.0264632.ref048","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1093\/ajcn\/46.1.72","article-title":"Viscosity of food gums determined in vitro related to their hypoglycemic actions","volume":"46","author":"CA Edwards","year":"1987","journal-title":"American J Clin Nutr"},{"key":"pone.0264632.ref049","first-page":"169","article-title":"Antioxidant activity and glucose diffusion relationship of traditional medicinal antihyperglycemic plant extracts","volume":"2","author":"F Asgharpour","year":"2013","journal-title":"Int J Mol Cell Med"},{"key":"pone.0264632.ref050","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1056\/NEJMra0906948","article-title":"Genomics, type 2 diabetes, and obesity","volume":"363","author":"MI McCarthy","year":"2010","journal-title":"New Eng J Med"},{"key":"pone.0264632.ref051","doi-asserted-by":"crossref","first-page":"806979","DOI":"10.1155\/2015\/806979","article-title":"The place of dipeptidyl peptidase-4 inhibitors in type 2 diabetes therapeutics: a \u201cme too\u201d or \u201cthe special one\u201d antidiabetic class?","volume":"2015","author":"R Godinho","year":"2015","journal-title":"J Diabetes Res"},{"key":"pone.0264632.ref052","doi-asserted-by":"crossref","first-page":"753","DOI":"10.4103\/2230-8210.141319","article-title":"Dipeptidyl peptidase-4 inhibitors: Novel mechanism of actions","volume":"18","author":"AK Singh","year":"2014","journal-title":"Indian J Endocrinol Metab"},{"key":"pone.0264632.ref053","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.3390\/molecules23081998","article-title":"DPP-IV inhibitory potentials of flavonol glycosides isolated from the seeds of lens culinaris: In vitro and molecular docking analyses","volume":"23","author":"BR Kim","year":"2018","journal-title":"Molecules"}],"container-title":["PLOS 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