An in vitro study reveals the nutraceutical potential of punicic acid relevant to diabetes via enhanced GLUT4 expression and adiponectin secretion

Abstract

The prevalence of diabetes and heart diseases is increasing in the world. Nutraceuticals of natural origin are gaining importance as an alternative to modern drugs for the management of metabolic syndrome. In the present study, punicic acid (PA), a major bioactive found in pomegranate seed, was subjected for biological characterization with respect to peroxisome proliferator-activated receptor gamma (PPARγ) agonist property in an in vitro system (3T3-L1 adipocytes). We evaluated the adipogenic potential of various concentrations (5, 10 and 30 μM) of PA by studying triglyceride accumulation and glycerol-3-phosphate dehydrogenase (GPDH) activity in adipocytes, which were found to be increased moderately compared with the positive control, i.e. rosiglitazone (RG). Glucose uptake activity (↑225.93% ± 2.55% for 30 μM of PA), and the prevention of reactive oxygen species (ROS) generation (↓57 ± 1.83% for 30 μM of PA) in adipocytes with PA were also evaluated. We also found that PA increased adiponectin secretion and upregulated GLUT4 expression and translocation in adipocytes. Molecular modelling studies revealed a high binding affinity of PA to the PPARγ ligand binding domain. An in vitro ligand binding assay based on time-resolved fluorescence resonance energy transfer (TR-FRET) also proved PA as a PPARγ agonist. Finally, we conclude that PA is a potential nutraceutical and should be encouraged for use both as a prophylactic and therapeutic agent.

Health Benefits of Punicic Acid: A Review

“…PA has also been shown to improve immune system development, helps in maintaining or enhancing the levels of CD4 + and CD8 + T lymphocyte, increasing immune response against viruses, and preventing or ameliorate type II diabetes and obesity (Bassaganya‐Riera ; Yuan and others ). Hence PA, by virtue of its PPARγ agonist characteristics, could be promoted as a prophylactic and therapeutic molecule (Anusree and others ).…”

Insulin resistance by TNF-α is associated with mitochondrial dysfunction in 3T3-L1 adipocytes and is ameliorated by punicic acid, a PPARγ agonist

“…Pomegranate extracts have been widely used for the management of metabolic syndromes and contain plenty of bioactive substances (Viladomiu et al, 2013). Punicic acid (PA), a polyunsaturated fatty acid, the main bioactive in pomegranate seed oil, is reported to have peroxisome proliferator-activated receptor gamma (PPARγ) agonist activity by different groups including us (Hontecillas et al, 2009;Bassaganya-Riera et al, 2011;Anusree et al, 2014). In the previous study we reported that PA is a PPARγ agonist with potent insulin stimulated glucose transport capacity and moderate adipogenic potential.…”

“…Pomegranate seed oil rich in punicic acid is reported to have DPPH, hydrogen peroxide, superoxide and nitric oxide radical scavenging activity (Prakash et al, 2013). In addition, PA prevents oxidative stress (Bousetta et al, 2009) and has adiponectin secretion stimulating property (Anusree et al, 2014). Overall existing data reveal excellent prospects of PA as a nutraceutical but need further evaluation with respect to its behaviour towards energy metabolism especially physiology of mitochondria as mitochondrial injury became an emerging target for insulin resistance .…”

Chebulagic acid from Terminalia chebula enhances insulin mediated glucose uptake in 3T3‐L1 adipocytes via PPARγ signaling pathway

“…Studies conducted by Shin et al () showed that esculetin from Fraxinus rhynchophylla significantly blocked the induction of PPARγ protein expression and inhibited adipocyte differentiation induced by troglitazone, a PPARγ agonist . Anusree et al (2013) have conducted studies on punicic acid (PA), a polyunsaturated fatty acid mainly found in pomegranate seed oil and found moderate adipogenic potential with enhanced glucose uptake and adiponectin secretion . In addition, there are reports of nutraceutical properties of some plant extracts relevant to diabetes via their adipogenic potential .…”