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

• 主要な著者: Erandi Ortiz-Barragán (著者), Samuel Estrada-Soto (著者), Abraham Giacoman-Martínez (著者), Francisco J. Alarcón-Aguilar (著者), Ángeles Fortis-Barrera (著者), Hugo Marquina-Rodríguez (著者), Emmanuel Gaona-Tovar (著者), Roberto Lazzarini-Lechuga (著者), Alfredo Suárez-Alonso (著者), Julio César Almanza-Pérez (著者)
• フォーマット: 図書
• 出版事項: MDPI AG, 2024-10-01T00:00:00Z.
• 主題: article
• オンライン･アクセス: Connect to this object online.
• Notes: 10.3390/ph17111451; 1424-8247
• Keywords: diabetes; hypolipidemic agents; flavonoids; PPARα; PPARγ; <i>Smilax dominguensis</i>; Medicine; R; Pharmacy and materia medica; RS1-441
• Source: Pharmaceuticals, Vol 17, Iss 11, p 1451 (2024)

<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.