Insulin Sensitization by PPARγ and GLUT-4 Overexpression/Translocation Mediates the Antidiabetic Effect of <i>Plantago australis</i>

• Main Authors: Samuel Estrada-Soto (Author), Kathia Ornelas-Mendoza (Author), Gabriel Navarrete-Vázquez (Author), Fabiola Chávez-Silva (Author), Julio Cesar Almanza-Pérez (Author), Rafael Villalobos-Molina (Author), Erandi Ortiz-Barragán (Author), Hilda Loza-Rodríguez (Author), Julio César Rivera-Leyva (Author), Angélica Flores-Flores (Author), Irene Perea-Arango (Author), Javier-German Rod (Author), Gabriela Ávila-Villarreal (Author)
• Format: Book
• Published: MDPI AG, 2023-04-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

<i>Plantago australis</i> Lam. Subsp. hirtella (Kunth) Rahn is a medicinal plant used as a diuretic, anti-inflammatory, antibacterial, throat cancer treatment and for the control of diabetes. <i>P. australis</i> was collected in the state of Morelos, México. The hydroalcoholic extract (HAE<i>Pa</i>) of <i>P. australis</i> was obtained by maceration and concentrated in vacuo. Once dry, it was evaluated through an oral glucose tolerance test (OGTT) in normoglycemic mice and in a non-insulin-dependent diabetic mice model. The expression of PPARγ and GLUT-4 mRNA was determined by rt-PCR, and GLUT-4 translocation was confirmed by confocal microscopy. The toxicological studies were conducted in accordance with the guidelines suggested by the OECD, sections 423 and 407, with some modifications. HAE<i>Pa</i> significantly decreased glycemia in OGTT curves, as well as in the experimental diabetes model compared to the vehicle group. In vitro tests showed that HAE<i>Pa</i> induced an α-glucosidase inhibition and increased PPARγ and GLUT-4 expression in cell culture. The LD₅₀ of HAE<i>Pa</i> was greater than 2000 mg/kg, and sub-chronic toxicity studies revealed that 100 mg/kg/day for 28 days did not generate toxicity. Finally, LC-MS analysis led to the identification of verbascoside, caffeic acid and geniposidic acid, and phytochemical approaches allowed for the isolation of ursolic acid, which showed significant PPARγ overexpression and augmented GLUT-4 translocation. In conclusion, HAE<i>Pa</i> induced significant antidiabetic action by insulin sensitization through PPARγ/GLUT-4 overexpression.

Item Description

10.3390/ph16040535
1424-8247