{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T23:47:24Z","timestamp":1764719244173,"version":"3.46.0"},"reference-count":42,"publisher":"Georg Thieme Verlag KG","issue":"15","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Planta Med"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Various Croton species have been traditionally used to treat diabetes; however, the antidiabetic potential and safety of many of these species remain poorly understood. This study evaluated the chemical composition, antihyperglycemic activity, insulin-sensitizing effect, and acute oral toxicity of C. ehrenbergii. Dichloromethane, ethyl acetate, n-butanol, and aqueous residue fractions were obtained via liquid\u2013liquid extraction from the hydroalcoholic extract obtained via maceration of the aerial parts. The primary compounds isolated from the fractions using column chromatography and identified by 1D nuclear magnetic resonance spectroscopy were 7,4\u2032-di-O-methylnaringenin, \u03b2-sitosterol, tiliroside, rutin, nicotiflorin, isoquercetin, and l-quebrachitol. The in vivo antihyperglycemic activity of these compounds was assessed using oral sucrose and glucose tolerance tests, and the most active fractions were evaluated ex\n          vivo to explore the mechanisms of action. The extract, fractions, and compounds were tested in vitro for their ability to inhibit \u03b1-glucosidase and protein tyrosine phosphatase 1B (PTP1B) as well as for their agonistic activity on PPAR-\u03b3. Tiliroside and nicotiflorin moderately inhibited PTP1B and \u03b1-glucosidase; whereas, l-quebrachitol acted as a PPAR-\u03b3 agonist. Acute oral toxicity studies indicated that the extract was safe at the tested dose. These results provide the first scientific evidence of the antihyperglycemic properties and preliminary safety of C. ehrenbergii.<\/jats:p>","DOI":"10.1055\/a-2689-5059","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T22:47:11Z","timestamp":1757026031000},"page":"923-932","source":"Crossref","is-referenced-by-count":0,"title":["In Vivo, Ex Vivo, and In Vitro Antihyperglycemic Evaluation of Croton ehrenbergii"],"prefix":"10.1055","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6817-8401","authenticated-orcid":false,"given":"M\u00f3nica Aide\u00e9","family":"D\u00edaz-Rom\u00e1n","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Qu\u00edmicas, IICBA, Universidad Aut\u00f3noma del Estado de Morelos, Cuernavaca, Morelos, M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8875-8734","authenticated-orcid":false,"given":"Maria Yolanda","family":"Rios","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Qu\u00edmicas, IICBA, Universidad Aut\u00f3noma del Estado de Morelos, Cuernavaca, Morelos, M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8306-1690","authenticated-orcid":false,"given":"Juan-Jos\u00e9","family":"Acevedo-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Facultad de Medicina, Universidad Aut\u00f3noma del Estado de Morelos, Cuernavaca, Morelos, M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3667-8828","authenticated-orcid":false,"given":"A. Berenice","family":"Aguilar-Guadarrama","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Qu\u00edmicas, IICBA, Universidad Aut\u00f3noma del Estado de Morelos, Cuernavaca, Morelos, M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2025,9,4]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.2337\/cd20-as01","article-title":"Standards of medical care in diabetes-2020 abridged for primary care providers","volume":"38","author":"American Diabetes Association","year":"2020","journal-title":"Clin Diabetes"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"S19","DOI":"10.2337\/dc23-S002","article-title":"Classification and diagnosis of diabetes: Standards of care in diabetes","volume":"46","author":"N A ElSayed","year":"2023","journal-title":"Diabetes Care"},{"volume-title":"Insulin Resistance. 2023 Aug 17","year":"2025","author":"A M Freeman","key":"ref3"},{"key":"ref4","first-page":"174","article-title":"PTP1B, a potential target of type 2 diabetes mellitus","volume":"05","author":"J Sun","year":"2016","journal-title":"Mol Biol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"599","DOI":"10.5483\/BMBRep.2014.47.11.174","article-title":"Revisiting PPAR\u03b3 as a target for the treatment of metabolic disorders","volume":"47","author":"S S Choi","year":"2014","journal-title":"BMB Rep"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.yjmcc.2016.09.002","article-title":"Role of protein tyrosine phosphatase 1B in cardiovascular diseases","volume":"101","author":"P A Thiebaut","year":"2016","journal-title":"J Mol Cell Cardiol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"e1125","DOI":"10.1038\/cddis.2014.90","article-title":"Pivotal role of protein tyrosine phosphatase 1B (PTP1B) in the macrophage response to pro-inflammatory and anti-inflammatory challenge","volume":"5","author":"P G Trav\u00e9s","year":"2014","journal-title":"Cell Death Dis"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"113990","DOI":"10.1016\/j.biopha.2022.113990","article-title":"Status of research on natural protein tyrosine phosphatase 1B inhibitors as potential antidiabetic agents: Update","volume":"157","author":"Z Liu","year":"2023","journal-title":"Biomed Pharmacother"},{"key":"ref9","first-page":"32","article-title":"In vitro alpha amylase inhibitory and anti-oxidant activities of ethanolic leaf extract of Croton bonplandianum","volume":"6","author":"G Keerthana","year":"2013","journal-title":"AJPCR"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1590\/S0103-50532007000100002","article-title":"Traditional uses, chemistry and pharmacology of Croton species (Euphorbiaceae)","volume":"18","author":"A Salatino","year":"2007","journal-title":"J Braz Chem Soc"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.4314\/tjpr.v13i11.9","article-title":"Evaluation of \u03b1-glucosidase inhibitory activity of dichloromethane and methanol extracts of Croton bonplandianum Baill","volume":"13","author":"M N Qaisar","year":"2014","journal-title":"Trop J Pharm Res"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1517\/14740338.2013.752813","article-title":"A review of the efficacy and safety of oral antidiabetic drugs","volume":"12","author":"S A Stein","year":"2013","journal-title":"Expert Opin Drug Saf"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1097\/MJT.0b013e3181ec9eb2","article-title":"Recent and emerging therapeutic medications in type 2 diabetes mellitus: Incretin-based, pramlintide, colesevelam, SGLT2 inhibitor, tagatose, succinobucol","volume":"20","author":"M C Lo","year":"2013","journal-title":"Am J Ther"},{"key":"ref14","first-page":"447","article-title":"In vivo antidiabetic activity of the aqueous leaf extract of Croton macrostachyus in alloxan induced diabetic mice","volume":"6","author":"W M Arika","year":"2015","journal-title":"Pharm Anal Acta"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.lfs.2016.04.027","article-title":"Triterpene derivative: A potential signaling pathway for the fern-9(11)-ene-2a, 3b-diol on insulin secretion in pancreatic islet","volume":"154","author":"G Da Luz","year":"2016","journal-title":"Life Sci"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1002\/ps.5336","article-title":"Phytotoxic and nematicide evaluation of Croton ehrenbergii (Euphorbiaceae)","volume":"75","author":"M Y Rios","year":"2019","journal-title":"Pest Manag Sci"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.3390\/molecules22091485","article-title":"Synthesis and biological activity of a novel O-alkyl derivatives of naringenin and their oximes","volume":"22","author":"J Kozlowska","year":"2017","journal-title":"Molecules"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"100","DOI":"10.31254\/phyto.2016.5302","article-title":"Isolation and identification of euphol and \u03b2-sitosterol from the dichloromethane extracts of Synadenium glaucescens","volume":"5","author":"A N Vitus","year":"2016","journal-title":"J Phytopharmacol"},{"key":"ref19","first-page":"206","article-title":"Isolation and 1H-NMR identification of a tiliroside from Odontonema strictum (Acanthaceae)","volume":"5","author":"P L Lokadi","year":"2016","journal-title":"J Pharmacogn Phytochem"},{"key":"ref20","first-page":"222","article-title":"Extraction of flavonoids and quantification of rutin from waste tobacco leaves","volume":"5","author":"F Fathiazad","year":"2006","journal-title":"Iran J Pharm Sci"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1590\/S0102-695X2013005000061","article-title":"Flavonoids from leaves of Mauritia flexuosa","volume":"24","author":"D M De Oliveira","year":"2013","journal-title":"Rev Bras Farmacogn"},{"key":"ref22","first-page":"177","article-title":"Phenolic compounds from the roots of Anchusa azurea var. azurea","volume":"10","author":"A Kuru\u00fcz\u00fcm-Uz","year":"2013","journal-title":"Turk J Phar Sci"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1002\/mrc.1611","article-title":"1H chemical shifts in NMR: Part 22\u2013Prediction of the 1H chemical shifts of alcohols, diols and inositols in solution, a conformational and solvation investigation","volume":"43","author":"R J Abraham","year":"2005","journal-title":"Magn Reson Chem"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1002\/mrc.3848","article-title":"1 H NMR analysis of O -methyl\u2010inositol isomers: A joint experimental and theoretical study","volume":"50","author":"M V de Almeida","year":"2012","journal-title":"Magn Reson Chem"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.cbi.2013.12.014","article-title":"Naringenin inhibits \u03b1-glucosidase activity: A promising strategy for the regulation of postprandial hyperglycemia in high fat diet fed streptozotocin induced diabetic rats","volume":"5","author":"D H Priscilla","year":"2014","journal-title":"Chem Biol Interact"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"10563","DOI":"10.3390\/molecules190710563","article-title":"Isolation and characterization of an \u03b1-glucosidase inhibitor from Musa spp. (Baxijiao) flowers","volume":"19","author":"Z Sheng","year":"2014","journal-title":"Molecules"},{"key":"ref27","first-page":"e10236","article-title":"Isolation, characterization of \u03b2-sitosterol from the herbal extracts and evaluation of in vitro anti-oxidant and anti-diabetic activities","volume":"13","author":"S Gomathi","year":"2024","journal-title":"J Microbiol Biotechnology Food Sci"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"382063","DOI":"10.1155\/2013\/382063","article-title":"Enzymes inhibition and antidiabetic effect of isolated constituents from Dillenia indica","volume":"2013","author":"S Kumar","year":"2013","journal-title":"Biomed Res Int"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"11463","DOI":"10.1021\/jf903083h","article-title":"Comparative evaluation of quercetin, isoquercetin and rutin as inhibitors of alpha-glucosidase","volume":"57","author":"Y Q Li","year":"2009","journal-title":"J Agric Food Chem"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"9326","DOI":"10.1039\/D4RA00666F","article-title":"Antimicrobial and alpha-glucosidase inhibitory flavonoid glycosides from the plant Mussaenda recurvata: in vitroand in silico approaches","volume":"14","author":"T T Ngoc Mai","year":"2024","journal-title":"RSC Adv"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.jff.2018.04.019","article-title":"Brazilian insulin plant as bifunctional food: Dual high-resolution PTP1B and a-glucosidase inhibition profiling combined with HPLC-HRMS-SPE-NMR for identification of antidietic compounds in Myrcia rubella Cambess","volume":"45","author":"R C Lemos-Lima","year":"2018","journal-title":"J Funct Foods"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"76","DOI":"10.4239\/wjd.v1.i3.76","article-title":"Metabolic effects of obesity: A review","volume":"1","author":"P Singla","year":"2010","journal-title":"World J Diabetes"},{"key":"ref33","first-page":"174","volume-title":"Insulin Resistance in Type 2 Diabetes","author":"M Roden","year":"2016"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"527","DOI":"10.15376\/biores.17.1.527-542","article-title":"Sea buckthorn leaf L-quebrachitol extract for improved glucose and lipid metabolism in insulin resistant hepG2 cells","volume":"17","author":"Y Mu","year":"2021","journal-title":"Bioresources"},{"key":"ref35","first-page":"1608","article-title":"Protein tyrosine phosphatase 1B as a target for the treatment of impaired glucose tolerance and type II diabetes","volume":"3","author":"G Liu","year":"2002","journal-title":"Curr Opin Investig Drugs"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"236","DOI":"10.4103\/2231-4040.90879","article-title":"The peroxisome proliferator-activated receptor: A family of nuclear receptors role in various diseases","volume":"2","author":"S Tyagi","year":"2011","journal-title":"J Adv Pharm Technol Res"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"105839","DOI":"10.1016\/j.fitote.2024.105839","article-title":"Phytochemical analysis and antihyperglycemic activity of Castilleja arvensis","volume":"174","author":"M A D\u00edaz-Rom\u00e1n","year":"2024","journal-title":"Fitoterapia"},{"volume-title":"Test No. 420: Acute Oral Toxicity \u2013 Fixed Dose Procedure. (8 February 2002)","author":"OECD","key":"ref38","doi-asserted-by":"publisher","DOI":"10.1787\/9789264070943-en"},{"key":"ref39","doi-asserted-by":"publisher","DOI":"10.2103\/rs.3.rs-558892\/v1","article-title":"Evaluation of the antihyperglycemic activity of Juglans Mollis and Hamelia Patents through in vitro and in vivo methods. PREPRINT (Version 1)","author":"G Granados-Guzm\u00e1n","year":"2021","journal-title":"Res Sq"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.1007\/s00394-017-1516-x","article-title":"Erythritol reduces small intestinal glucose absorption, increases muscle glucose uptake, improves glucose metabolic enzymes activities and increases expression of Glut-4 and IRS-1 in type 2 diabetic rats","volume":"57","author":"C I Chukwuma","year":"2018","journal-title":"Eur J Nut"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1055\/s-2005-861289","article-title":"Efficient analysis of hepatic glucose output and insulin action using a liver slice culture system","volume":"37","author":"R Buettner","year":"2005","journal-title":"Horm Metab Res"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"701261","DOI":"10.1155\/2012\/701261","article-title":"In Vitro screening of medicinal plants used in Mexico as antidiabetics with glucosidase and lipase inhibitory activities","volume":"2012","author":"G Ram\u00edrez","year":"2012","journal-title":"Evid Based Complement Alternat Med"}],"container-title":["Planta Medica"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2689-5059.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T23:43:14Z","timestamp":1764718994000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2689-5059"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,4]]},"references-count":42,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2025,12,2]]},"published-print":{"date-parts":[[2025,12]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2689-5059","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0032-0943","1439-0221"],"issn-type":[{"type":"print","value":"0032-0943"},{"type":"electronic","value":"1439-0221"}],"subject":[],"published":{"date-parts":[[2025,9,4]]}}}