Program

PO4-8-25

STUDY IN VIVO, IN SILICO AND IN VITRO OF ALPHA-AMYRIN AND LUPEOL, COMPOUNDS ISOLATED OF HIBISCUS SABDARIFFA L., AS DUAL AGONISTS OF PPARdelta/gamma

[Speaker] Abraham Giacoman:1
[Co-author] Alejandro Zamilpa-Alvarez:2, Sergio N. Hidalgo-Figueroa:3, Gabriel Navarrete-Vazquez:4, Ruben Roman-Ramos:5, Francisco J. Alarcon-Aguilar:5, Julio C. Almanza-Perez:5
1:Posgrado en Biologia experimental. Universidad Autonoma Metropolitana. Mexico, 2:Centro de Investigacion Biomedica del Sur. Instituto Mexicano del Seguro Social, Mexico, 3:Instituto Potosino de Ciencia y Tecnologia. S. L. P., Mexico, 4:Facultad de Farmacia, Universidad Autonoma del Estado de Morelos, Cuernavaca, Mexico, 5:Lab. Farmacologia. Depto. Ciencias de la Salud. Univerisdad Autonoma Metropolitana-Iztapalapa, Mexico

BACKGROUND. Hibiscus sabdariffa L. has been traditionally used in stews and drinks. Pharmacological studies support its anti-inflammatory, anti-oxidant, diuretic, antihypertensive, anti-adipogenic and anti-diabetic effects. These two latest activities supporting the participation of PPARdelta and PPARgamma. PPARs are factors of transcription that modulate the lipid and glucose metabolism, key elements for increasing insulin sensitivity. Therefore, development of new PPARdelta/gamma dual agonists from H. sabdariffa should be considered. The aim of this research was evaluate the dichloromethane extract from H. sabdariffa (HS-DCM) in anti-hyperglycemic test, and evaluate constitutive compounds with potential dual agonist of PPARdelta/gamma.
METHODS. Oral glucose tolerance tests (OGTT) were performed in normal CD1 mice, which received HS-DCM, and pioglitazone (positive control). HS-DCM was fractionated, obtaining four fractions which were evaluated on the expression of PPARdelta/gamma in myocytes C2C12. Fraction F10 was selected and fractioned, obtaining two sub-fractions that were analyzed by high performance liquid chromatography coupled to mass spectrometry. The principal identified compounds were: linoleic acid, oleic acid, and palmitic acid were found in F10-1; alpha-amyrin and lupeol in F10-2. With these compounds was performed a molecular docking. Finally, evaluate the effect on mRNA expression for PPARdelta, PPARgamma, FATP and GLUT4 by qPCR-RT was evaluated. In addition protein of PPARdelta and PPARgamma were determined by western blot.
RESULTS. In the (OGTT), the HS-DCM avoided hyperglycemic peak like pioglitazone. F10, F10-1 and F10-2 exhibited PPARdelta/gamma dual activity. By molecular docking, Linoleic acid, palmitic acid, oleic acid, alpha-amyrin and lupeol exhibited high affinity for both isoforms PPARdelta/gamma. Linoleic acid, oleic acid, alpha-amyrin and lupeol, incremented the expression of PPARdelta, PPARgamma, and downstream genes FATP and GLUT 4 and PPARdelta and PPARgamma protein. Palmitic acid had no effect on PPARdelta/gamma expression.
CONCLUSIONS: HS-DCM had a similar anti-hyperglycemic effect to pioglitazone. Molecular docking suggested that linoleic acid, oleic acid, alpha-amyrin, and lupeol act as PPARdelta/gamma dual agonists. alpha-amyrin and lupeol shown higher activity than pioglitazone and L-165041 (PPARdelta agonist) in mRNA and protein expression. These compounds should be considered for the development of new treatments for DM2 and other diseases associated with metabolic syndrome.

Advanced Search