Insulin-Sensitizing Properties of Decoctions from Leaves, Stems, and Roots of <i>Cucumis prophetarum</i> L.
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
Affiliations
Zewdie Mekonnen
Department of Biochemistry, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa P. O. Box 9086, Ethiopia
Giuseppe Petito
Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania, 81100 Caserta, Italy
Getasew Shitaye
Department of Biomedical Sciences, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar P. O. Box 79, Ethiopia
Gianluca D’Abrosca
Department of Clinical and Experimental Medicine, University of Foggia, Viale Pinto 1, 71100 Foggia, Italy
Belete Adefris Legesse
Center for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa), College of Health Sciences, Addis Ababa University, Addis Ababa P. O. Box 9086, Ethiopia
Sisay Addisu
Department of Biochemistry, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa P. O. Box 9086, Ethiopia
Maurizio Ragni
Center for Study and Research on Obesity, Department of Medical Biotechnology and Translational Medicine, University of Milan, 20133 Milan, Italy
Antonia Lanni
Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania, 81100 Caserta, Italy
Roberto Fattorusso
Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania, 81100 Caserta, Italy
Carla Isernia
Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania, 81100 Caserta, Italy
Lara Comune
Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania, 81100 Caserta, Italy
Simona Piccolella
Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania, 81100 Caserta, Italy
Severina Pacifico
Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania, 81100 Caserta, Italy
Rosalba Senese
Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania, 81100 Caserta, Italy
Gaetano Malgieri
Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania, 81100 Caserta, Italy
Solomon Tebeje Gizaw
Department of Biochemistry, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa P. O. Box 9086, Ethiopia
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 Cucumis prophetarum 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 C-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.
