Insulin-Sensitizing Properties of Decoctions from Leaves, Stems, and Roots of <i>Cucumis prophetarum</i> L.

Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by insulin resistance and impaired beta-cell secretory function. Since existing treatments often present side effects based on different mechanisms, alternative therapeutic options are needed. In this scenario, the present study firs...

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Main Authors: Zewdie Mekonnen, Giuseppe Petito, Getasew Shitaye, Gianluca D’Abrosca, Belete Adefris Legesse, Sisay Addisu, Maurizio Ragni, Antonia Lanni, Roberto Fattorusso, Carla Isernia, Lara Comune, Simona Piccolella, Severina Pacifico, Rosalba Senese, Gaetano Malgieri, Solomon Tebeje Gizaw
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/1/98
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author Zewdie Mekonnen
Giuseppe Petito
Getasew Shitaye
Gianluca D’Abrosca
Belete Adefris Legesse
Sisay Addisu
Maurizio Ragni
Antonia Lanni
Roberto Fattorusso
Carla Isernia
Lara Comune
Simona Piccolella
Severina Pacifico
Rosalba Senese
Gaetano Malgieri
Solomon Tebeje Gizaw
author_facet Zewdie Mekonnen
Giuseppe Petito
Getasew Shitaye
Gianluca D’Abrosca
Belete Adefris Legesse
Sisay Addisu
Maurizio Ragni
Antonia Lanni
Roberto Fattorusso
Carla Isernia
Lara Comune
Simona Piccolella
Severina Pacifico
Rosalba Senese
Gaetano Malgieri
Solomon Tebeje Gizaw
author_sort Zewdie Mekonnen
collection DOAJ
description Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by insulin resistance and impaired beta-cell secretory function. Since existing treatments often present side effects based on different mechanisms, alternative therapeutic options are needed. In this scenario, the present study first evaluates the cytotoxicity of decoctions from the leaves, stems, and roots of <i>Cucumis prophetarum</i> L. on HepG2 and L6C5 cells. The extracts were chemically investigated by UV–Vis and ATR-FTIR spectroscopic techniques and by ultra high-performance chromatographic techniques, coupled with high-resolution mass spectrometry. Briefly, decoctions from the leaves and stems were mainly composed of apigenin <i>C</i>-glycosides, while the root decoction was rich in raffinose and cucumegastigmane II. To evaluate the insulin-sensitizing properties of the extracts in insulin-resistant L6 myoblasts, an evaluation by Western blot analysis of the proteins in the insulin signaling pathway was then performed. Particularly, key proteins of insulin signaling were investigated, i.e., insulin receptor substrate (IRS-1), protein kinase B (PKB/AKT), and glycogen synthase kinase-3 (GSK-3β), which have gained considerable attention from scientists for the treatment of diabetes. Under all conditions tested, the three decoctions showed low cytotoxicity. The stem and root decoction (300 μg/mL) resulted in a significant increase in the levels of p-IRS-1 (Tyr612), GSK3β (Ser9), and p-AMPK (Thr172) compared to those of the palmitic acid-treated group, and the leaf decoction resulted an increase in the level of p-IRS-1 (Tyr612) and p-AMPK (Thr172) and a decrease in p-GSK3β (Ser9) compared to the levels for the palmitic acid-treated group. The root decoction also reduced the level of p-mToR (Ser2448). Overall, the acquired data demonstrate the effect of reducing insulin resistance induced by the investigated decoctions, opening new scenarios for the evaluation of these effects aimed at counteracting diabetes and related diseases in animal models.
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spelling doaj-art-160e203caec9409b97535b1318ee81e22025-01-10T13:18:52ZengMDPI AGMolecules1420-30492024-12-013019810.3390/molecules30010098Insulin-Sensitizing Properties of Decoctions from Leaves, Stems, and Roots of <i>Cucumis prophetarum</i> L.Zewdie Mekonnen0Giuseppe Petito1Getasew Shitaye2Gianluca D’Abrosca3Belete Adefris Legesse4Sisay Addisu5Maurizio Ragni6Antonia Lanni7Roberto Fattorusso8Carla Isernia9Lara Comune10Simona Piccolella11Severina Pacifico12Rosalba Senese13Gaetano Malgieri14Solomon Tebeje Gizaw15Department of Biochemistry, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa P. O. Box 9086, EthiopiaDepartment of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania, 81100 Caserta, ItalyDepartment of Biomedical Sciences, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar P. O. Box 79, EthiopiaDepartment of Clinical and Experimental Medicine, University of Foggia, Viale Pinto 1, 71100 Foggia, ItalyCenter for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa), College of Health Sciences, Addis Ababa University, Addis Ababa P. O. Box 9086, EthiopiaDepartment of Biochemistry, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa P. O. Box 9086, EthiopiaCenter for Study and Research on Obesity, Department of Medical Biotechnology and Translational Medicine, University of Milan, 20133 Milan, ItalyDepartment of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania, 81100 Caserta, ItalyDepartment of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania, 81100 Caserta, ItalyDepartment of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania, 81100 Caserta, ItalyDepartment of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania, 81100 Caserta, ItalyDepartment of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania, 81100 Caserta, ItalyDepartment of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania, 81100 Caserta, ItalyDepartment of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania, 81100 Caserta, ItalyDepartment of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania, 81100 Caserta, ItalyDepartment of Biochemistry, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa P. O. Box 9086, EthiopiaType 2 diabetes mellitus (T2DM) is a chronic disease characterized by insulin resistance and impaired beta-cell secretory function. Since existing treatments often present side effects based on different mechanisms, alternative therapeutic options are needed. In this scenario, the present study first evaluates the cytotoxicity of decoctions from the leaves, stems, and roots of <i>Cucumis prophetarum</i> L. on HepG2 and L6C5 cells. The extracts were chemically investigated by UV–Vis and ATR-FTIR spectroscopic techniques and by ultra high-performance chromatographic techniques, coupled with high-resolution mass spectrometry. Briefly, decoctions from the leaves and stems were mainly composed of apigenin <i>C</i>-glycosides, while the root decoction was rich in raffinose and cucumegastigmane II. To evaluate the insulin-sensitizing properties of the extracts in insulin-resistant L6 myoblasts, an evaluation by Western blot analysis of the proteins in the insulin signaling pathway was then performed. Particularly, key proteins of insulin signaling were investigated, i.e., insulin receptor substrate (IRS-1), protein kinase B (PKB/AKT), and glycogen synthase kinase-3 (GSK-3β), which have gained considerable attention from scientists for the treatment of diabetes. Under all conditions tested, the three decoctions showed low cytotoxicity. The stem and root decoction (300 μg/mL) resulted in a significant increase in the levels of p-IRS-1 (Tyr612), GSK3β (Ser9), and p-AMPK (Thr172) compared to those of the palmitic acid-treated group, and the leaf decoction resulted an increase in the level of p-IRS-1 (Tyr612) and p-AMPK (Thr172) and a decrease in p-GSK3β (Ser9) compared to the levels for the palmitic acid-treated group. The root decoction also reduced the level of p-mToR (Ser2448). Overall, the acquired data demonstrate the effect of reducing insulin resistance induced by the investigated decoctions, opening new scenarios for the evaluation of these effects aimed at counteracting diabetes and related diseases in animal models.https://www.mdpi.com/1420-3049/30/1/98diabetes mellitusmedicinal plants<i>Cucumis prophetarum</i> L.apigenin <i>C</i>-glycosidesantidiabetic effectcytotoxicity
spellingShingle Zewdie Mekonnen
Giuseppe Petito
Getasew Shitaye
Gianluca D’Abrosca
Belete Adefris Legesse
Sisay Addisu
Maurizio Ragni
Antonia Lanni
Roberto Fattorusso
Carla Isernia
Lara Comune
Simona Piccolella
Severina Pacifico
Rosalba Senese
Gaetano Malgieri
Solomon Tebeje Gizaw
Insulin-Sensitizing Properties of Decoctions from Leaves, Stems, and Roots of <i>Cucumis prophetarum</i> L.
Molecules
diabetes mellitus
medicinal plants
<i>Cucumis prophetarum</i> L.
apigenin <i>C</i>-glycosides
antidiabetic effect
cytotoxicity
title Insulin-Sensitizing Properties of Decoctions from Leaves, Stems, and Roots of <i>Cucumis prophetarum</i> L.
title_full Insulin-Sensitizing Properties of Decoctions from Leaves, Stems, and Roots of <i>Cucumis prophetarum</i> L.
title_fullStr Insulin-Sensitizing Properties of Decoctions from Leaves, Stems, and Roots of <i>Cucumis prophetarum</i> L.
title_full_unstemmed Insulin-Sensitizing Properties of Decoctions from Leaves, Stems, and Roots of <i>Cucumis prophetarum</i> L.
title_short Insulin-Sensitizing Properties of Decoctions from Leaves, Stems, and Roots of <i>Cucumis prophetarum</i> L.
title_sort insulin sensitizing properties of decoctions from leaves stems and roots of i cucumis prophetarum i l
topic diabetes mellitus
medicinal plants
<i>Cucumis prophetarum</i> L.
apigenin <i>C</i>-glycosides
antidiabetic effect
cytotoxicity
url https://www.mdpi.com/1420-3049/30/1/98
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