Colocynth (Citrullus colocynthis) Flesh Extract Suppresses Adipogenesis by Down-Regulating Adipogenic Transcription Factors and Their Target Genes in 3T3-L1 Preadipocytes

Abstract

Citrullus colocynthis, a member of the Cucurbitaceae family, is widely distributed in North Africa. The fruits are recognized for their wide range of medicinal uses and promising pharmaceutical potential. The present study aimed to investigate the anti-obesity effect of the ethanol extract of colocynth flesh (FCEE) in 3T3-L1 cells following treatment at different doses. The viability of 3T3-L1 preadipocytes was analyzed via MTT assay and triglycerides were stained with Oil red O to assess lipid accumulation. Additionally, adipogenesis-related gene expression was quantified via qRT-PCR. FCEE (0 - 150 μg/mL) dose-dependently suppressed intracellular triglyceride accumulation during the adipogenesis by 23% and 66% at 100 and 150 μg/mL, respectively, but did not affect cell viability. Analysis of the time-dependence of the effect of FCEE demonstrated that the greatest anti-adipogenic activity was observed during the early stages of differentiation. FCEE also decreased GPDH activity in a dose-dependent manner, with 98% decrease observed at 150 μg/mL. In addition, at same range of FCEE concentrations, the main transcription factors, including CCAAT/enhancer binding protein α (C/EBPα), peroxisome proliferator activated receptor γ (PPARγ), and sterol regulatory element-binding protein 1c (SREBP-1c), were downregulated by 90%, 89%, and 89%, respectively at 150 μg/mL. As these are the master regulators of adipogenesis. The inhibition of their downstream target genes was also observed. Colocynth may be useful in the treatment of obesity owing to its powerful effects on fat, which result in changes to adipocyte differentiation and fat mobilization.