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

Farromeque Vásquez, Sherley Catherine; Arbeláez, Luisa González; Rojano, Benjamín; Schinella, Guillermo; Maiztegui, Bárbara; Francini, Flavio

doi:10.3390/plants14050745

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

by

Sherley Catherine Farromeque Vásquez

¹,

Luisa González Arbeláez

²,

Benjamín Rojano

³

,

Guillermo Schinella

^4,5

,

Bárbara Maiztegui

^1,† and

Flavio Francini

^1,*,†

¹

CENEXA (Centre for Experimental and Applied Endocrinology—UNLP CONICET CCT La Plata—CEAS CICPBA), School of Medicine, Street 60 and 120, La Plata 1900, Argentina

²

CIC (Centre for Cardiovascular Research—UNLP CONICET CCT La Plata), School of Medicine, Street 60 and 120, La Plata 1900, Argentina

³

Universidad Nacional de Colombia, Sede Medellín, Facultad de Ciencias, Laboratorio de Ciencia de Alimentos, Medellín 050012, Colombia

⁴

UNLP—School of Medicine, Cathedra Basic Pharmacology, Street 60 and 120, La Plata 1900, Argentina

⁵

UNAJ-CICPBA, Institute of Health Sciences, Av. Calchaquí 6200, Florencio Varela 1888, Argentina

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Plants 2025, 14(5), 745; https://doi.org/10.3390/plants14050745

Submission received: 26 December 2024 / Revised: 11 February 2025 / Accepted: 14 February 2025 / Published: 1 March 2025

(This article belongs to the Special Issue Natural Products of Medicinal Plants: Isolation, Purification and Bioactivity Evaluation)

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Abstract

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 Oxandra cf. xylopioides (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.p.). 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 -IR-, IRS1/2, PI3K), oxidative stress (SOD-2, GPx, GSR, 3’-nitrotyrosine), inflammation (TNF-α, IL-1β, PAI-1), mitochondrial function (Bcl-2, mtTFA, PGC-1α), 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 (p < 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).

Keywords: prediabetes; Oxandra cf. xylopioides; pancreatic islets; isoespintanol

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MDPI and ACS Style

Farromeque Vásquez, S.C.; Arbeláez, L.G.; Rojano, B.; Schinella, G.; Maiztegui, B.; Francini, F. Isoespintanol Isolated from Oxandra cf. xylopioides (Annonaceae) Leaves Ameliorates Pancreatic Dysfunction and Improves Insulin Sensitivity in Murine Model of Fructose-Induced Prediabetes. Plants 2025, 14, 745. https://doi.org/10.3390/plants14050745

AMA Style

Farromeque Vásquez SC, Arbeláez LG, Rojano B, Schinella G, Maiztegui B, Francini F. Isoespintanol Isolated from Oxandra cf. xylopioides (Annonaceae) Leaves Ameliorates Pancreatic Dysfunction and Improves Insulin Sensitivity in Murine Model of Fructose-Induced Prediabetes. Plants. 2025; 14(5):745. https://doi.org/10.3390/plants14050745

Chicago/Turabian Style

Farromeque Vásquez, Sherley Catherine, Luisa González Arbeláez, Benjamín Rojano, Guillermo Schinella, Bárbara Maiztegui, and Flavio Francini. 2025. "Isoespintanol Isolated from Oxandra cf. xylopioides (Annonaceae) Leaves Ameliorates Pancreatic Dysfunction and Improves Insulin Sensitivity in Murine Model of Fructose-Induced Prediabetes" Plants 14, no. 5: 745. https://doi.org/10.3390/plants14050745

APA Style

Farromeque Vásquez, S. C., Arbeláez, L. G., Rojano, B., Schinella, G., Maiztegui, B., & Francini, F. (2025). Isoespintanol Isolated from Oxandra cf. xylopioides (Annonaceae) Leaves Ameliorates Pancreatic Dysfunction and Improves Insulin Sensitivity in Murine Model of Fructose-Induced Prediabetes. Plants, 14(5), 745. https://doi.org/10.3390/plants14050745

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

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