Isoespintanol Isolated from <i>Oxandra</i> cf. <i>xylopioides</i> (Annonaceae) Leaves Ameliorates Pancreatic Dysfunction and Improves Insulin Sensitivity in Murine Model of Fructose-Induced Prediabetes

In rats, a fructose-rich diet triggers endocrine-metabolic disturbances similar to those present in human prediabetes. We evaluated the protective effect of isoespintanol, a monoterpene isolated from <i>Oxandra</i> cf. <i>xylopioides</i> (Annonaceae), on pancreatic islet. Rat...

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Main Authors: Sherley Catherine Farromeque Vásquez, Luisa González Arbeláez, Benjamín Rojano, Guillermo Schinella, Bárbara Maiztegui, Flavio Francini
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Plants
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Online Access:https://www.mdpi.com/2223-7747/14/5/745
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author Sherley Catherine Farromeque Vásquez
Luisa González Arbeláez
Benjamín Rojano
Guillermo Schinella
Bárbara Maiztegui
Flavio Francini
author_facet Sherley Catherine Farromeque Vásquez
Luisa González Arbeláez
Benjamín Rojano
Guillermo Schinella
Bárbara Maiztegui
Flavio Francini
author_sort Sherley Catherine Farromeque Vásquez
collection DOAJ
description In rats, a fructose-rich diet triggers endocrine-metabolic disturbances similar to those present in human prediabetes. We evaluated the protective effect of isoespintanol, a monoterpene isolated from <i>Oxandra</i> cf. <i>xylopioides</i> (Annonaceae), on pancreatic islet. Rats were kept for three weeks with a standard commercial diet and tap water (C), plus 10% fructose (F), or F plus isoespintanol (I; 10 mg/kg, <i>i.p</i>.). Glycemia, triglyceridemia, total cholesterol, HDL-cholesterol, insulin resistance index (IRX), and glucose tolerance tests were determined. Glucose-stimulated insulin secretion (GSIS) and gene expression of insulin signalling mediators (insulin receptor -<i>IR-, IRS1/2, PI3K</i>), oxidative stress (<i>SOD-2, GPx, GSR</i>, 3’-nitrotyrosine), inflammation (<i>TNF-α, IL-1β, PAI-1</i>), mitochondrial function (<i>Bcl-2, mtTFA, PGC-1α</i>), and apoptosis markers were evaluated in pancreatic islets. The F group increased triglyceridemia, non-HDL-cholesterol, and IRX, and decreased HDL-cholesterol and impaired glucose tolerance, with alterations reversed by isoespintanol administration (<i>p</i> < 0.05). Isoespintanol normalized higher GSIS recorded in the F group. F decreased mRNA levels of insulin signalling mediators and mitochondrial function markers, and increased the expression of inflammatory, apoptotic, and oxidative stress markers, alterations that were significantly reversed by isoespintanol. Current results suggest that isoespintanol improved insular oxidative stress and inflammation by affecting the IR-PI3K pathway, which plays a pivotal role in insulin resistance development, underlying its therapeutic potential for the prevention of type 2 diabetes before its onset (prediabetes).
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spelling doaj-art-efc66706a0dd450fa6ff4f9b68da5a3b2025-08-20T02:52:38ZengMDPI AGPlants2223-77472025-03-0114574510.3390/plants14050745Isoespintanol Isolated from <i>Oxandra</i> cf. <i>xylopioides</i> (Annonaceae) Leaves Ameliorates Pancreatic Dysfunction and Improves Insulin Sensitivity in Murine Model of Fructose-Induced PrediabetesSherley Catherine Farromeque Vásquez0Luisa González Arbeláez1Benjamín Rojano2Guillermo Schinella3Bárbara Maiztegui4Flavio Francini5CENEXA (Centre for Experimental and Applied Endocrinology—UNLP CONICET CCT La Plata—CEAS CICPBA), School of Medicine, Street 60 and 120, La Plata 1900, ArgentinaCIC (Centre for Cardiovascular Research—UNLP CONICET CCT La Plata), School of Medicine, Street 60 and 120, La Plata 1900, ArgentinaUniversidad Nacional de Colombia, Sede Medellín, Facultad de Ciencias, Laboratorio de Ciencia de Alimentos, Medellín 050012, ColombiaUNLP—School of Medicine, Cathedra Basic Pharmacology, Street 60 and 120, La Plata 1900, ArgentinaCENEXA (Centre for Experimental and Applied Endocrinology—UNLP CONICET CCT La Plata—CEAS CICPBA), School of Medicine, Street 60 and 120, La Plata 1900, ArgentinaCENEXA (Centre for Experimental and Applied Endocrinology—UNLP CONICET CCT La Plata—CEAS CICPBA), School of Medicine, Street 60 and 120, La Plata 1900, ArgentinaIn rats, a fructose-rich diet triggers endocrine-metabolic disturbances similar to those present in human prediabetes. We evaluated the protective effect of isoespintanol, a monoterpene isolated from <i>Oxandra</i> cf. <i>xylopioides</i> (Annonaceae), on pancreatic islet. Rats were kept for three weeks with a standard commercial diet and tap water (C), plus 10% fructose (F), or F plus isoespintanol (I; 10 mg/kg, <i>i.p</i>.). Glycemia, triglyceridemia, total cholesterol, HDL-cholesterol, insulin resistance index (IRX), and glucose tolerance tests were determined. Glucose-stimulated insulin secretion (GSIS) and gene expression of insulin signalling mediators (insulin receptor -<i>IR-, IRS1/2, PI3K</i>), oxidative stress (<i>SOD-2, GPx, GSR</i>, 3’-nitrotyrosine), inflammation (<i>TNF-α, IL-1β, PAI-1</i>), mitochondrial function (<i>Bcl-2, mtTFA, PGC-1α</i>), and apoptosis markers were evaluated in pancreatic islets. The F group increased triglyceridemia, non-HDL-cholesterol, and IRX, and decreased HDL-cholesterol and impaired glucose tolerance, with alterations reversed by isoespintanol administration (<i>p</i> < 0.05). Isoespintanol normalized higher GSIS recorded in the F group. F decreased mRNA levels of insulin signalling mediators and mitochondrial function markers, and increased the expression of inflammatory, apoptotic, and oxidative stress markers, alterations that were significantly reversed by isoespintanol. Current results suggest that isoespintanol improved insular oxidative stress and inflammation by affecting the IR-PI3K pathway, which plays a pivotal role in insulin resistance development, underlying its therapeutic potential for the prevention of type 2 diabetes before its onset (prediabetes).https://www.mdpi.com/2223-7747/14/5/745prediabetes<i>Oxandra</i> cf. <i>xylopioides</i>pancreatic isletsisoespintanol
spellingShingle Sherley Catherine Farromeque Vásquez
Luisa González Arbeláez
Benjamín Rojano
Guillermo Schinella
Bárbara Maiztegui
Flavio Francini
Isoespintanol Isolated from <i>Oxandra</i> cf. <i>xylopioides</i> (Annonaceae) Leaves Ameliorates Pancreatic Dysfunction and Improves Insulin Sensitivity in Murine Model of Fructose-Induced Prediabetes
Plants
prediabetes
<i>Oxandra</i> cf. <i>xylopioides</i>
pancreatic islets
isoespintanol
title Isoespintanol Isolated from <i>Oxandra</i> cf. <i>xylopioides</i> (Annonaceae) Leaves Ameliorates Pancreatic Dysfunction and Improves Insulin Sensitivity in Murine Model of Fructose-Induced Prediabetes
title_full Isoespintanol Isolated from <i>Oxandra</i> cf. <i>xylopioides</i> (Annonaceae) Leaves Ameliorates Pancreatic Dysfunction and Improves Insulin Sensitivity in Murine Model of Fructose-Induced Prediabetes
title_fullStr Isoespintanol Isolated from <i>Oxandra</i> cf. <i>xylopioides</i> (Annonaceae) Leaves Ameliorates Pancreatic Dysfunction and Improves Insulin Sensitivity in Murine Model of Fructose-Induced Prediabetes
title_full_unstemmed Isoespintanol Isolated from <i>Oxandra</i> cf. <i>xylopioides</i> (Annonaceae) Leaves Ameliorates Pancreatic Dysfunction and Improves Insulin Sensitivity in Murine Model of Fructose-Induced Prediabetes
title_short Isoespintanol Isolated from <i>Oxandra</i> cf. <i>xylopioides</i> (Annonaceae) Leaves Ameliorates Pancreatic Dysfunction and Improves Insulin Sensitivity in Murine Model of Fructose-Induced Prediabetes
title_sort isoespintanol isolated from i oxandra i cf i xylopioides i annonaceae leaves ameliorates pancreatic dysfunction and improves insulin sensitivity in murine model of fructose induced prediabetes
topic prediabetes
<i>Oxandra</i> cf. <i>xylopioides</i>
pancreatic islets
isoespintanol
url https://www.mdpi.com/2223-7747/14/5/745
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