Comparative Study: Biguanide-, Sulfonamide-, and Natural Agent-Based Interventions in an In Vivo Experimental Diabetes Model

<i>Background/Objectives:</i> In the context of diabetes, a multifactorial metabolic disorder with significant clinical implications, the present study investigates the hypoglycemic effects of a synthetic sulfonamide (S) administered individually and in combination with <i>Salvia o...

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Main Authors: Iulian Tătaru, Ioannis Gardikiotis, Carmen Lidia Chiţescu, Oana-Maria Dragostin, Maria Dragan, Cerasela Gîrd, Alexandra-Simona Zamfir, Simona Iacob (Ciobotaru), Rodica Vatcu, Catalina Daniela Stan, Carmen Lăcrămioara Zamfir
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Medicina
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Online Access:https://www.mdpi.com/1648-9144/61/7/1151
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author Iulian Tătaru
Ioannis Gardikiotis
Carmen Lidia Chiţescu
Oana-Maria Dragostin
Maria Dragan
Cerasela Gîrd
Alexandra-Simona Zamfir
Simona Iacob (Ciobotaru)
Rodica Vatcu
Catalina Daniela Stan
Carmen Lăcrămioara Zamfir
author_facet Iulian Tătaru
Ioannis Gardikiotis
Carmen Lidia Chiţescu
Oana-Maria Dragostin
Maria Dragan
Cerasela Gîrd
Alexandra-Simona Zamfir
Simona Iacob (Ciobotaru)
Rodica Vatcu
Catalina Daniela Stan
Carmen Lăcrămioara Zamfir
author_sort Iulian Tătaru
collection DOAJ
description <i>Background/Objectives:</i> In the context of diabetes, a multifactorial metabolic disorder with significant clinical implications, the present study investigates the hypoglycemic effects of a synthetic sulfonamide (S) administered individually and in combination with <i>Salvia officinalis</i> extract, compared to metformin as a standard therapeutic agent. <i>Methods</i>: An in vivo model of experimentally induced diabetes using alloxan was applied to Wistar female rats, divided into six experimental groups, including a healthy control group and a diabetes-induced, untreated group. Plasma concentrations of metformin and sulfonamide were quantified by high-performance liquid chromatography. The plasma steady-state concentrations of the pharmaceutical agents and their correlation with hypoglycemic effect were evaluated. <i>Results</i>: The combination of the synthetic sulfonamide (S) with <i>Salvia officinalis</i> extract resulted in the greatest reduction in blood glucose level (average value of 50.2%) compared to S (40.6%) or metformin (36.4%). All treatments demonstrated statistically significant differences in blood glucose levels compared to the diabetes-induced untreated group (<i>p</i> < 0.05). Pharmacokinetic analysis revealed a larger volume of distribution for the synthetic sulfonamide S (23.92 ± 8.40 L) compared to metformin (16.07 ± 5.60 L), consistent with its physicochemical properties. No significant correlation was found between plasma drug levels and glycemic response (<i>p</i> > 0.05). <i>Conclusions</i>: Our findings support the potential of combining standard therapeutic agents with natural alternatives such as <i>Salvia officinalis</i> to achieve improved glycemic control through complementary mechanisms. To the best of our knowledge, this is the first in vivo study to evaluate the combined effects of a sulfonylurea-type compound and <i>Salvia officinalis</i> extract in a diabetic animal model.
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spelling doaj-art-ad95dee720a54834b81e23912303ded52025-08-20T02:47:07ZengMDPI AGMedicina1010-660X1648-91442025-06-01617115110.3390/medicina61071151Comparative Study: Biguanide-, Sulfonamide-, and Natural Agent-Based Interventions in an In Vivo Experimental Diabetes ModelIulian Tătaru0Ioannis Gardikiotis1Carmen Lidia Chiţescu2Oana-Maria Dragostin3Maria Dragan4Cerasela Gîrd5Alexandra-Simona Zamfir6Simona Iacob (Ciobotaru)7Rodica Vatcu8Catalina Daniela Stan9Carmen Lăcrămioara Zamfir10Department of Morphofunctional Sciences I, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, RomaniaCEMEX—Advanced Center for Research and Development in Experimental Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700454 Iași, RomaniaDepartment of Pharmaceutical Sciences, Research Centre in the Medical-Pharmaceutical Field, Faculty of Medicine and Pharmacy, “Dunarea de Jos” University of Galati, 800201 Galati, RomaniaDepartment of Pharmaceutical Sciences, Research Centre in the Medical-Pharmaceutical Field, Faculty of Medicine and Pharmacy, “Dunarea de Jos” University of Galati, 800201 Galati, RomaniaDepartment of Pharmaceutical Sciences II, Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy, 16 Universității Street, 700115 Iași, RomaniaDepartment of Pharmacognosy, Phytochemistry and Phytotherapy, Faculty of Pharmacy, University of Medicine and Pharmacy “Carol Davila”, 050474 Bucharest, RomaniaDepartment of Medical Sciences III, “Grigore T. Popa” University of Medicine and Pharmacy, 16 Universității Street, 700115 Iași, RomaniaDepartment of Pharmaceutical Sciences, Research Centre in the Medical-Pharmaceutical Field, Faculty of Medicine and Pharmacy, “Dunarea de Jos” University of Galati, 800201 Galati, RomaniaDepartment of Pharmaceutical Sciences, Research Centre in the Medical-Pharmaceutical Field, Faculty of Medicine and Pharmacy, “Dunarea de Jos” University of Galati, 800201 Galati, RomaniaDepartment of Pharmaceutical Sciences II, Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy, 16 Universității Street, 700115 Iași, RomaniaDepartment of Morphofunctional Sciences I, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania<i>Background/Objectives:</i> In the context of diabetes, a multifactorial metabolic disorder with significant clinical implications, the present study investigates the hypoglycemic effects of a synthetic sulfonamide (S) administered individually and in combination with <i>Salvia officinalis</i> extract, compared to metformin as a standard therapeutic agent. <i>Methods</i>: An in vivo model of experimentally induced diabetes using alloxan was applied to Wistar female rats, divided into six experimental groups, including a healthy control group and a diabetes-induced, untreated group. Plasma concentrations of metformin and sulfonamide were quantified by high-performance liquid chromatography. The plasma steady-state concentrations of the pharmaceutical agents and their correlation with hypoglycemic effect were evaluated. <i>Results</i>: The combination of the synthetic sulfonamide (S) with <i>Salvia officinalis</i> extract resulted in the greatest reduction in blood glucose level (average value of 50.2%) compared to S (40.6%) or metformin (36.4%). All treatments demonstrated statistically significant differences in blood glucose levels compared to the diabetes-induced untreated group (<i>p</i> < 0.05). Pharmacokinetic analysis revealed a larger volume of distribution for the synthetic sulfonamide S (23.92 ± 8.40 L) compared to metformin (16.07 ± 5.60 L), consistent with its physicochemical properties. No significant correlation was found between plasma drug levels and glycemic response (<i>p</i> > 0.05). <i>Conclusions</i>: Our findings support the potential of combining standard therapeutic agents with natural alternatives such as <i>Salvia officinalis</i> to achieve improved glycemic control through complementary mechanisms. To the best of our knowledge, this is the first in vivo study to evaluate the combined effects of a sulfonylurea-type compound and <i>Salvia officinalis</i> extract in a diabetic animal model.https://www.mdpi.com/1648-9144/61/7/1151experimental diabetesphytotherapyhypoglycemic effectpharmacokinetic parameters
spellingShingle Iulian Tătaru
Ioannis Gardikiotis
Carmen Lidia Chiţescu
Oana-Maria Dragostin
Maria Dragan
Cerasela Gîrd
Alexandra-Simona Zamfir
Simona Iacob (Ciobotaru)
Rodica Vatcu
Catalina Daniela Stan
Carmen Lăcrămioara Zamfir
Comparative Study: Biguanide-, Sulfonamide-, and Natural Agent-Based Interventions in an In Vivo Experimental Diabetes Model
Medicina
experimental diabetes
phytotherapy
hypoglycemic effect
pharmacokinetic parameters
title Comparative Study: Biguanide-, Sulfonamide-, and Natural Agent-Based Interventions in an In Vivo Experimental Diabetes Model
title_full Comparative Study: Biguanide-, Sulfonamide-, and Natural Agent-Based Interventions in an In Vivo Experimental Diabetes Model
title_fullStr Comparative Study: Biguanide-, Sulfonamide-, and Natural Agent-Based Interventions in an In Vivo Experimental Diabetes Model
title_full_unstemmed Comparative Study: Biguanide-, Sulfonamide-, and Natural Agent-Based Interventions in an In Vivo Experimental Diabetes Model
title_short Comparative Study: Biguanide-, Sulfonamide-, and Natural Agent-Based Interventions in an In Vivo Experimental Diabetes Model
title_sort comparative study biguanide sulfonamide and natural agent based interventions in an in vivo experimental diabetes model
topic experimental diabetes
phytotherapy
hypoglycemic effect
pharmacokinetic parameters
url https://www.mdpi.com/1648-9144/61/7/1151
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