Effect of aqueous extract of Uncaria tomentosa against lipotoxicity induced by palmitate in skeletal myotubes: prospects for treatment of insulin resistance

• Grant number: 22/16702-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2023
• End date: December 31, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Viviane Abreu Nunes Cerqueira Dantas
• Grantee: Athirson Moraes Chanavat
• Host Institution: Escola de Artes, Ciências e Humanidades (EACH). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Type 2 diabetes mellitus (T2DM) is characterized by relative hypoinsulinemia, often associated with dyslipidemia, which corresponds to increased concentrations of triglycerides and, consequently, fatty acids in tissues such as skeletal muscle, whichcan culminate in oxidative stress. The use of phytotherapics, such as Uncaria tomentosa (Ut), has been proposed as an auxiliary treatment to patients diagnosed with T2DM, considering its possibility of overlapping with the conventional therapy. The aim of this work is to evaluate the effect of Ut aqueous extract on oxidative stress and cell death induced by free fatty acid palmitate (PA), in skeletal myotubesof the C2C12 lineage. Cells will be cultured in Dulbecco modified Eagle medium (DMEM), supplemented with 10% fetal bovine serum (FBS) or with 3,5% horse serum (HS) to induce skeletal muscle cells into differentiation, at 37°C, in a humidified atmosphere and 5% CO 2 . Cells will be incubated with PA at different concentrations (10 to 1000 ¼M), in the presence or absence of Ut 250 ¼g/ml aqueousextract, for 2, 6 or 24 h. The reactive oxygen species (ROS) production will be evaluated using the fluorescent marker 2',7'-dichlorofluorescein diacetate (DCFDA) and the expression of genes PERK, EIF2±, ATF4, CHOP, IRS-1, AKT and GSK3² will be evaluated by real-time quantitative PCR (real-time qPCR). The results generated in this work may result in new approaches for the insulin resistance andT2DM complementary treatment, including the proposition of using the Ut herbal medicine as an auxiliary treatment in the management of the disease.