<i>Cucurbita ficifolia</i> Bouché Regulates the Metabolism of Carbohydrates and Lipids in Liver by Activation of PPAR<i>α</i> without Affectation on PPAR<i>γ in Vivo</i> and <i>in Vitro</i>

Abstract

Diabetes mellitus control in Mexico is practiced by using antidiabetic agents and, by empirical way using medicinal plants. Cucurbita ficifolia ( C. ficifolia ) has been attributed with hypoglycemic, hypotriglyceridemic, and anti-inflam - matory effects, and D-chiro-inositol (DCI), 4-hydroxybenzoic acid, and β -sitosterol were proposed as active principles. The last two compounds were suggested as activators of two transcription factors, PPAR α and PPAR γ , in C2C12 myocytes, which participate in β -oxidation of fatty acids and insulin sensitivity. However, the involvement of the hepatocytic and adipocytic PPARs in the effects of C. ficifolia has not yet been explored. This research aimed to determine the effects of C. ficifolia on PPAR α , PPAR γ , and inflammatory cytokines in streptozotocin (STZ)-induced diabetes mice, HepG2 hepatocytes and 3T3-L1 adipocytes, implicating two additional cell types associated with metabolism of carbohydrates and lipids. STZ-induced diabetes mice received C. ficifolia (200 mg/kg/day) for 30 days, measuring serum cytokines (TNF- α and IL-6). RNA was extracted from liver. Besides, HepG2 and 3T3-L1 cells were incubated (24 h) with C. ficifolia (0.078 mM DCI), using pioglitazone or fenofibrate as controls. RNA was also extracted from cells and PCR in real-time was performed to determinate PPAR α and PPAR γ expression. In diabetic animals, C. ficifolia decreased glycemia and body weight, decreasing the expression level of TNF- α and IL-6. In addition, C. ficifolia increased PPAR α expression in liver of diabetic animals, in HepG2 and 3T3-L1 cells; PPAR γ expression only significantly increased in HepG2 cells. The data suggest that the effects on the glycemia and lipids of C. ficifolia and its anti-inflammatory effects imply, besides skeletal muscle cells, hepatic and adipocytic PPAR α activation, without affectation on PPAR γ . PPARs regulation by C. ficifolia may improve the metabolic dysfunctions associated with metabolic disease, controlling the intake, activation, and oxidation of fatty acids and lipid storage.