Antihyperglycemic and Hypolipidemic Activities of Flavonoids Isolated from Smilax Dominguensis Mediated by Peroxisome Proliferator-Activated Receptors

• Main Authors: Erandi Ortiz-Barragán (Author), Samuel Estrada-Soto (Author), Abraham Giacoman-Martínez (Author), Francisco J. Alarcón-Aguilar (Author), Ángeles Fortis-Barrera (Author), Hugo Marquina-Rodríguez (Author), Emmanuel Gaona-Tovar (Author), Roberto Lazzarini-Lechuga (Author), Alfredo Suárez-Alonso (Author), Julio César Almanza-Pérez (Author)
• Format: Book
• Published: MDPI AG, 2024-10-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

<b>Background/objetives</b>: Mexican people use Smilax dominguensis as a traditional medicine for diabetes control. Some reports have shown an anti-hyperglycemic effect in animal models. In the current research, a chemical bio-guided fractionation in vitro and in silico was performed to identify compounds with anti-hyperglycemic and hypolipidemic effects through PPARγ/α dual agonist activity because they regulate genes involved in energy storage and burning, such as GLUT4 and FATP. <b>Methods</b>: The S. dominguensis extract was evaluated in mice through oral glucose tolerance tests. The bioactive extract was fractionated by open-column chromatography, and seven final fractions (F1-F7) were obtained and evaluated. C2C12 myoblasts were treated with the fractions, and the mRNA expression levels of PPARs, GLUT-4, and FATP were quantified. The most active fractions were evaluated on GLUT-4 translocation and lipid storage in C2C12 cells and 3T3-L1 adipocytes, respectively. <b>Results</b>: The F3 fraction increased the expressions of PPARγ, GLUT-4, PPARα, and FATP, and it induced GLUT-4 translocation and decreased lipid storage. F3 was then analyzed by NMR, identifying three flavonoids: luteolin, apigenin, and kaempferol. These compounds were analyzed by molecular docking and on PPAR expressions. Luteolin, apigenin, and kaempferol produced a discrete increase in the mRNA expression of PPARs. Luteolin and kaempferol also decreased lipid storage. <b>Conclusions</b>: Our findings indicate that the compounds identified in S. dominguensis exhibit dual agonist activity on PPARγ/PPARα and have the potential for the development of new therapeutic agents helpful in diabetes, obesity, or metabolic syndrome.

Item Description

10.3390/ph17111451
1424-8247