GLUT4 translocation in C2C12 myoblasts and primary mouse hepatocytes by an antihyperglycemic flavone from Tillandsia usneoides
Autor: | Ángeles Fortis-Barrera, Hilda Loza-Rodriguez, Miguel Angel Zavala-Sánchez, María Flores-Cruz, Alejandro Zamilpa-Alvarez, Francisco Javier Alarcón-Aguilar, Luis Enrique Gómez-Quiroz, Gerardo Blancas-Flores, Jhovan Eduardo Miranda-Nuñez, Soraya Salas-Silva |
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Rok vydání: | 2021 |
Předmět: |
Phytochemicals
Pharmaceutical Science Fractionation Pharmacology Cell Line Myoblasts 03 medical and health sciences Mice 0302 clinical medicine Drug Discovery medicine Bioassay Animals Hypoglycemic Agents 030304 developmental biology 0303 health sciences Glucose tolerance test Glucose Transporter Type 4 medicine.diagnostic_test biology Chemistry Glucose transporter Lipid metabolism Carbohydrate Flavones Complementary and alternative medicine Diabetes Mellitus Type 2 030220 oncology & carcinogenesis biology.protein Hepatocytes Molecular Medicine Tillandsia C2C12 GLUT4 |
Zdroj: | Phytomedicine : international journal of phytotherapy and phytopharmacology. 89 |
ISSN: | 1618-095X |
Popis: | Background Type 2 Diabetes (T2D) is characterized by deregulation in carbohydrate and lipid metabolism, with a very high mortality rate. Glucose Transporter type 4 (GLUT4) plays a crucial role in T2D and represents a therapeutic target of interest. Tillandsia usneoides (T. usneoides) is a plant used as a remedy for diabetes. T. usneoides decreased blood glucose in different experimental models. However, the involvement of GLUT4 in this effect has not yet been explored. Purpose This study aimed to investigate whether any component in T. usneoides might participate in the effect on blood glucose through a bioassay-guided fractionation, testing its potential antihyperglycemic effect in mice, as well as its influence on GLUT4 translocation in C2C12 myoblasts and primary hepatocytes. Methods The aqueous extract and the Ethyl Acetate fraction (TU-AcOEt) of T. usneoides were evaluated in a hypoglycemic activity bioassay and in the glucose tolerance test in CD-1 mice. TU-AcOEt was fractionated, obtaining five fractions that were studied in an additional glucose tolerance test. C1F3 was fractioned again, and its fractions (C2F9-12, C2F22-25, and C2F38-44) were examined by HPLC. The C2F38-44 fraction was analyzed by Mass Spectrometry (MS) and subjected to additional fractionation. The fraction C3F6-9 was explored by Nuclear Magnetic Resonance (NMR), resulting in 5,7,4´-trihydroxy-3,6,3´,5´-tetramethoxyflavone (Flav1). Subsequently, a viability test was performed to evaluate the cytotoxic effect of Flav1 and fractions C2F9-12, C2F22-25. C2F38-44, and C3F30-41 in C2C12 myoblasts and primary mouse hepatocytes. Confocal microscopy was also performed to assess the effect of Flav1 and fractions on GLUT4 translocation. Results The TU-AcOEt fraction exhibited a hypoglycemic and antihyperglycemic effect in mice, and its fractionation resulted in five fractions, among which fraction C1F3 decreased blood glucose. MS and NMR analysis revealed the presence of Flav1. Finally, Flav1 significantly promoted the translocation of GLUT4 in C2C12 myoblasts and primary hepatocytes. Conclusion To date, Flav1 has not been reported to have activity in GLUT4; this study provides evidence that T. usneoides is a plant with the potential to develop novel therapeutic agents for the control of T2D. |
Databáze: | OpenAIRE |
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